Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism.

Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism. Copyright 2007 John Wiley & Sons, Ltd.

Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. A randomized controlled trial.

Hirsutism in polycystic ovarian syndrome (PCOS), consequent to elevated androgen levels leads to significant cosmetic and psychological problems. Recent research in Turkey has shown that spearmint tea has antiandrogenic properties in females with hirsutism. No research has yet been undertaken to assess whether a reduction in androgen levels brought about by spearmint tea, translates to a clinical improvement in the degree of hirsutism. This study was a two centre, 30 day randomized controlled trial. Forty two volunteers were randomized to take spearmint tea twice a day for a 1 month period and compared with a placebo herbal tea. At 0, 15 and 30 days of the study serum androgen hormone levels and gonadotrophins were checked, the degree of hirsutism was clinically rated using the Ferriman-Galwey score and a questionnaire (the modified DQLI = Dermatology Quality of Life Index) was used to assess improvements in the level of self-reported hirsutism. Forty one of 42 patients completed the study. Free and total testosterone levels were significantly reduced over the 30 day period in the spearmint tea group (p < 0.05). LH and FSH also increased (p < 0.05). Patient's subjective assessments of their degree of hirsutism scored by the modified DQLI were significantly reduced in the spearmint tea group (p < 0.05). There was, however, no significant reduction in the objective Ferriman-Galwey ratings of hirsutism between the two trial groups over the trial duration (p = 0.12). There was a clear and significant alteration in the relevant hormone levels. This is associated clinically with a reduction in the self-reported degree of hirsutism but unfortunately not with the objectively rated score. It was demonstrated and confirmed that spearmint has antiandrogen properties, the simple fact that this does not clearly translate into clinical practice is due to the relationship between androgen hormones and follicular hair growth and cell turnover time. Simply put, the study duration was not long enough. The original studies from Turkey were in fact only 5 days long. The time taken for hirsutism to resolve is significant and a much longer future study is proposed as the preliminary findings are encouraging that spearmint has the potential for use as a helpful and natural treatment for hirsutism in PCOS. (c) 2009 John Wiley & Sons, Ltd.

The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome.

Herbal remedies, particularly peppermint, have been reported to be helpful in controlling symptoms of irritable bowel syndrome (IBS). We conducted a randomized double-blind placebo-controlled study on 90 outpatients with IBS. Subjects took one capsule of enteric-coated, delayed-release peppermint oil (Colpermin) or placebo three times daily for 8 weeks. We visited patients after the first, fourth, and eighth weeks and evaluated their symptoms and quality of life. The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls (P < 0.001). The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls. Furthermore, Colpermin significantly improved the quality of life. There was no significant adverse reaction. Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort.

A near fatal case of high dose peppermint oil ingestion- Lessons learnt

Peppermint oil is easily available as a constituent of medicines. A near fatal case due to ingestion of toxic dose of oral peppermint oil is being reported. The patient came in a comatosed state and was in shock. She was managed with mechanical ventilation and ionotropes. Her vital parameters reached normal within 8 hours and became conscious by 24 hours. The side effects of peppermint oil are considered to be mild but this case report warns that ingestion of oral toxic doses of peppermint oil could be dangerous.

Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial.

INTRODUCTION: The use of peppermint oil in treating the irritable bowel syndrome has been studied with variable results probably due to the presence of patients affected by small intestinal bacterial overgrowth, lactose intolerance or celiac disease that may have symptoms similar to irritable bowel syndrome. AIM: The aim of the study was to test the effectiveness of enteric-coated peppermint oil in patients with irritable bowel syndrome in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease were excluded. METHODS: Fifty-seven patients with irritable bowel syndrome according to the Rome II criteria, with normal lactose and lactulose breath tests and negative antibody screening for celiac disease, were treated with peppermint oil (two enteric-coated capsules twice per day or placebo) for 4 weeks in a double blind study. The symptoms were assessed before therapy (T(0)), after the first 4 weeks of therapy (T(4)) and 4 weeks after the end of therapy (T(8)). The symptoms evaluated were: abdominal bloating, abdominal pain or discomfort, diarrhoea, constipation, feeling of incomplete evacuation, pain at defecation, passage of gas or mucus and urgency at defecation. For each symptom intensity and frequency from 0 to 4 were scored. The total irritable bowel syndrome symptoms score was also calculated as the mean value of the sum of the average of the intensity and frequency scores of each symptom. RESULTS: At T(4), 75% of the patients in the peppermint oil group showed a >50% reduction of basal (T(0)) total irritable bowel syndrome symptoms score compared with 38% in the placebo group (P<0.009). With peppermint oil at T(4) and at T(8) compared with T(0) a statistically significant reduction of the total irritable bowel syndrome symptoms score was found (T(0): 2.19+/-0.13, T(4): 1.07+/-0.10*, T(8): 1.60+/-0.10*, *P<0.01 compared with T(0), mean+/-S.E.M.), while no change was found with the placebo. CONCLUSION: A 4 weeks treatment with peppermint oil improves abdominal symptoms in patients with irritable bowel syndrome.

The effects of peppermint on exercise performance

Background Enhancing athletic performance is a great desire among the athletes, coaches and researchers. Mint is one of the most famous natural herbs used for its analgesic, anti-inflammatory, antispasmodic, antioxidant, and vasoconstrictor effects. Even though inhaling mint aroma in athletes has been investigated, there were no significant effects on the exercise performance. Methods Twelve healthy male students every day consumed one 500 ml bottle of mineral water, containing 0.05 ml peppermint essential oil for ten days. Blood pressure, heart rate, and spirometry parameters including forced vital capacity (FVC), peak expiratory flow rate (PEF), and peak inspiratory flow (PIF) were determined one day before, and after the supplementation period. Participants underwent a treadmill-based exercise test with metabolic gas analysis and ventilation measurement using the Bruce protocol. Results The FVC (4.57 ± 0.90 vs. 4.79 ± 0.84; p < 0.001), PEF (8.50 ± 0.94 vs. 8.87 ± 0.92; p < 0.01), and PIF (5.71 ± 1.16 vs. 6.58 ±1.08; p < 0.005) significantly changed after ten days of supplementation. Exercise performance evaluated by time to exhaustion (664.5 ± 114.2 vs. 830.2 ± 129.8 s), work (78.34 ±32.84 vs. 118.7 ± 47.38 KJ), and power (114.3 ± 24.24 vs. 139.4 ± 27.80 KW) significantly increased (p < 0.001). In addition, the results of respiratory gas analysis exhibited significant differences in VO2 (2.74 ± 0.40 vs. 3.03 ± 0.351 L/min; p < 0.001), and VCO2 (3.08 ± 0.47 vs. 3.73 ± 0.518 L/min; p < 0.001). Conclusions The results of the experiment support the effectiveness of peppermint essential oil on the exercise performance, gas analysis, spirometry parameters, blood pressure, and respiratory rate in the young male students. Relaxation of bronchial smooth muscles, increase in the ventilation and brain oxygen concentration, and decrease in the blood lactate level are the most plausible explanations.

Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis.

GOALS: The aim of this study was to assess the efficacy and safety of enteric-coated peppermint oil capsules compared with placebo for the treatment of active irritable bowel syndrome (IBS). BACKGROUND: IBS is a common disorder that is often encountered in clinical practice. Medical interventions are limited and the focus is on symptom control. STUDY: Randomized placebo-controlled trials with a minimum treatment duration of 2 weeks were considered for inclusion. Cross-over studies that provided outcome data before the first cross-over were included. A literature search upto February 2013 identified all applicable randomized-controlled trials. Study quality was evaluated using the Cochrane risk of bias tool. Outcomes included global improvement of IBS symptoms, improvement in abdominal pain, and adverse events. Outcomes were analyzed using an intention-to-treat approach. RESULTS: Nine studies that evaluated 726 patients were identified. The risk of bias was low for most of the factors assessed. Peppermint oil was found to be significantly superior to placebo for global improvement of IBS symptoms (5 studies, 392 patients, relative risk 2.23; 95% confidence interval, 1.78-2.81) and improvement in abdominal pain (5 studies, 357 patients, relative risk 2.14; 95% confidence interval, 1.64-2.79). Although peppermint oil patients were significantly more likely to experience an adverse event, such events were mild and transient in nature. The most commonly reported adverse event was heartburn. CONCLUSIONS: Peppermint oil is a safe and effective short-term treatment for IBS. Future studies should assess the long-term efficacy and safety of peppermint oil and its efficacy relative to other IBS treatments including antidepressants and antispasmodic drugs.

Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam).

The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated "ipomoein," which was reported by Jones and Gersdorff, (1931). Later, "ipomoein" was renamed "sporamin" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. Copyright © 2012 Elsevier Inc. All rights reserved.

Controlled breathing with or without peppermint aromatherapy for postoperative nausea and/or vomiting symptom relief: a randomized controlled trial.

PURPOSE: With little scientific evidence to support use of aromatherapy for postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated controlled breathing with peppermint aromatherapy (AR) and controlled breathing alone (CB) for PONV relief. DESIGN: A single blind randomized control trial design was used. METHODS: On initial PONV complaint, symptomatic subjects received either CB (n = 16) or AR (n = 26) intervention based on randomization at enrollment. A second treatment was repeated at 5 minutes if indicated. Final assessment occurred 10 minutes post initial treatment. Rescue medication was offered for persistent symptoms. FINDINGS: Among eligible subjects, PONV incidence was 21.4% (42/196). Gender was the only risk factor contributing to PONV symptoms (P = .0024). Though not statistically significant, CB was more efficacious than AR, 62.5% versus 57.7%, respectively. CONCLUSIONS: CB can be initiated without delay as an alternative to prescribed antiemetics. Data also support use of peppermint AR in conjunction with CB for PONV relief. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Effects of peppermint teas on plasma testosterone, follicle-stimulating hormone, and luteinizing hormone levels and testicular tissue in rats.

OBJECTIVES: To justify the effects of Mentha piperita labiatae and Mentha spicata labiatae herbal teas on plasma total testosterone, luteinizing hormone, and follicle-stimulating hormone levels and testicular histologic features. We performed this study because of major complaints in our area from men about the adverse effects of these herbs on male reproductive function. METHODS: The experimental study included 48 male Wistar albino rats (body weight 200 to 250 g). The rats were randomized into four groups of 12 rats each. The control group was given commercial drinking water, and the experimental groups were given 20 g/L M. piperita tea, 20 g/L M. spicata tea, or 40 g/L M. spicata tea. RESULTS: The follicle-stimulating hormone and luteinizing hormone levels had increased and total testosterone levels had decreased in the experimental groups compared with the control group; the differences were statistically significant. Also, the Johnsen testicular biopsy scores were significantly different statistically between the experimental groups and the control group. Although the mean seminiferous tubular diameter of the experimental groups was relatively greater than in the control group, the difference was not statistically significant. The only effects of M. piperita on testicular tissue was segmental maturation arrest in the seminiferous tubules; however, the effects of M. spicata extended from maturation arrest to diffuse germ cell aplasia in relation to the dose. CONCLUSIONS: Despite the beneficial effects of M. piperita and M. spicata in digestion, we should also be aware of the toxic effects when the herbs are not used in the recommended fashion or at the recommended dose.

Improved performance on clerical tasks associated with administration of peppermint odor.

Previous research indicates the presence of certain odors is associated with enhanced task performance. The present study investigated use of peppermint odor during typing performance, memorization, and alphabetization. Participants completed the protocol twice--once with peppermint odor present and once without. Analysis indicated significant differences in the gross speed, net speed, and accuracy on the typing task, with odor associated with improved performance. Alphabetization also improved significantly under the odor condition but not typing duration or memorization. These results suggest peppermint odor may promote a general arousal of attention, so participants stay focused on their task and increase performance.

Several culinary and medicinal herbs are important sources of dietary antioxidants.

We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.

Topical vitamin A treatment of recalcitrant common warts.

BACKGROUND: Common warts (verruca vulgaris) are benign epithelial proliferations associated with human papillomavirus (HPV) infection. Salicylic acid and cryotherapy are the most frequent treatments for common warts, but can be painful and cause scarring, and have high failure and recrudescence rates. Topical vitamin A has been shown to be a successful treatment of common warts in prior informal studies. CASE: The subject is a healthy, physically-active 30 old female with a 9 year history of common warts on the back of the right hand. The warts resisted treatment with salicylic acid, apple cider vinegar and an over-the-counter blend of essential oils marketed for the treatment of warts. Daily topical application of natural vitamin A derived from fish liver oil (25,000 IU) led to replacement of all the warts with normal skin. Most of the smaller warts had been replaced by 70 days. A large wart on the middle knuckle required 6 months of vitamin A treatment to resolve completely. CONCLUSION: Retinoids should be further investigated in controlled studies to determine their effectiveness in treating common warts and the broad range of other benign and cancerous lesions induced by HPVs.

Examination of the effectiveness of peppermint aromatherapy on nausea in women post C-section.

PURPOSE: This study examined the effect of peppermint spirits on postoperative nausea in women following a scheduled C-section. DESIGN: A pretest-posttest research design with three groups was used. The peppermint group inhaled peppermint spirits, the placebo aromatherapy control group inhaled an inert placebo, green-colored sterile water, and the standard antiemetic therapy control group received standard antiemetics, usually intravenous ondansetron or promethazine suppositories. METHODS: Women were randomly assigned to a group on admission to the hospital. If they became nauseated, nurses on the mother-baby unit assessed their nausea (baseline), administered the assigned intervention, and then reassessed participants' nausea 2 and 5 minutes after the initial intervention. Participants rated their nausea using a 6-point nausea scale. FINDINGS: Thirty-five participants became nauseated post-operatively. Participants in all three intervention groups had similar levels of nausea at baseline. The nausea levels of participants in the peppermint spirits group were significantly lower than those of participants in the other two groups 2 and 5 minutes after the initial intervention. CONCLUSIONS: Peppermint spirits may be a useful adjunct in the treatment of postoperative nausea. This study should be replicated with more participants, using a variety of aromatherapies to treat nausea in participants with different preoperative diagnoses.

Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.

Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

A systematic screening of total antioxidants in dietary plants.

A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.

Accidental bullous phototoxic reactions to bergamot aromatherapy oil.

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.

Determination of citrulline in watermelon rind.

Watermelon (Citrullus vulgaris Schrad.) is a natural and rich source of the non-essential amino acid citrulline. Citrulline is used in the nitric oxide system in humans and has potential antioxidant and vasodilatation roles. A method using gas chromatography-mass spectrometry (GC-MS) was developed to separate citrulline from glutamic acid, which co-elute when analyzed by high performance liquid chromatography. Watermelons were analyzed by GC-MS to determine the citrulline content among varieties, types, flesh colors, and tissues. Citrulline content ranged from 3.9 to 28.5 mg/g dry weight (dwt) and was similar between seeded and seedless types (16.6 and 20.3 mg/g dwt, respectively). Red flesh watermelons had slightly less citrulline than the yellow or orange flesh watermelons (7.4, 28.5 and 14.2 mg/g dwt, respectively). Rind contained more citrulline than flesh on a dry weight basis (24.7 and 16.7 mg/g dwt, respectively) but a little less on a fresh weight (fwt) basis (1.3 and 1.9 mg/g fwt, respectively). These results indicate that watermelon rind, an underutilized agricultural waste, offers a source of natural citrulline.

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry ...

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy.

Migraine treatment has evolved from the realms of the supernatural into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, now known as 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side-effects.

gamma-Irradiation dose: effects on baby-leaf spinach ascorbic acid, carotenoids, folate, alpha-tocopherol, and phylloquinone concentrations.

Ionizing radiation of fruits and vegetables, in the form of gamma rays or electron beams, is effective in overcoming quarantine barriers in trade and prolonging shelf life, but a void of information persists on ionizing radiation effects of vitamin profiles in individual foods. Baby-leaf spinach from commercial cultivars, flat-leafed 'Lazio' and crinkled-leaf 'Samish', was grown, harvested, and surface sanitized according to industry practices. Baby-leaf spinach of each cultivar was packaged under air or N(2) atmosphere, representing industry practices, then exposed to cesium-137 gamma-radiation at 0.0, 0.5, 1.0, 1.5, or 2.0 kGy. Following irradiation, leaf tissues were assayed for vitamin (C, E, K, B(9)) and carotenoid (lutein/zeaxanthin, neoxanthin, violoxanthin, and beta-carotene) concentrations. Atmospheres by irradiation had little consistent effect, but N(2) versus air was associated with elevated dihydroascorbic acid levels. Four phytonutrients (vitamins B(9), E, and K and neoxanthin) exhibited little or no change in concentration with increasing doses of irradiation. However, total ascorbic acid (vitamin C), free ascorbic acid, lutein/zeaxanthin, violaxanthin, and beta-carotene all were significantly reduced at 2.0 kGy and, depending on cultivar, were affected at lesser doses of 0.5 and 1.5 kGy. Dihydroascorbic acid, the most affected compound and an indicator of stress, likely due to irradiation-generated oxidative radicals, increased with increasing irradiation doses >0.5 kGy.

Aluminium and other elements in selected herbal tea plant species and their infusions.

The determination of Al, B, Cu, Fe, Mn, Ni, P, Zn and Ca, K, Mg by inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectroscopy (FAAS), respectively, in digests and infusions of Hibiscus sabdariffa (petals), Rosa canina (receptacles), Ginkgo biloba (leaves), Cymbopogon citratus (leaves), Aloe vera (leaves) and Panax ginseng (roots) was carried out in this study. Particular attention has been given to Al and heavy metals for the identification of possible raw material contaminants, their transformation into the infusion and for predicting their eventual role in the human diet during daily consumption. Additionally, Ion Chromatography (IC) speciation of Al in the leachates was carried out. In dry herbs, hibiscus and ginkgo appeared to contain the greatest contents of Al, Fe, K, Mn, Ni, Zn and B, Mg, P, respectively. A. vera contained the highest amount of Ca and highest values of Cu and P were observed in ginseng. In infusions, the topmost concentrations of Al, B, Cu, Fe, P, K, Mn, Ni, Zn were detected in those prepared from hibiscus petals, Ca from aloe leaves and Mg from leaves of ginkgo. According to a possible daily consumption exceeding 1 L, hibiscus decoction was identified as potentially dietetically significant in the content of certain elements. It seems to be possibly one of the top contributors of B from food (up to 5.5±0.2 mg/L). The Mg contained in the infusion (up to 106±5 mg/L) may be a contributor in the attenuation of blood pressure. A high amount of accessible Mn (up to 17.4±1.1 mg/L) can probably have an adverse effect in humans. The total Al allowance (up to 1.2±0.1 mg/L) suggests that no more than 1 L of the hibiscus infusion should be consumed per day by sensitive individuals including pregnant women and should be completely excluded from the diet of children under 6 months of age and children with chronic renal failure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus).

The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet.

Multitargeting by turmeric, the golden spice: From kitchen to clinic.

Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2-5% of turmeric, is perhaps the most-studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin-independent. Cell-based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell-signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial.

Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o...

Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.

[6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system.

β-Amyloid (Aβ) is involved in the formation of senile plaques, the typical neuropathological marker for Alzheimer's disease (AD) and has been reported to cause apoptosis in neurons via oxidative and/or nitrosative stress. In this study, we have investigated the neuroprotective effect and molecular mechanism of [6]-gingerol, a pungent ingredient of ginger against Αβ(25-35)-induced oxidative and/or nitrosative cell death in SH-SY5Y cells. [6]-Gingerol pretreatment protected against Aβ(25-35)-induced cytotoxicity and apoptotic cell death such as DNA fragmentation, disruption of mitochondrial membrane potential, elevated Bax/Bcl-2 ratio, and activation of caspase-3. To elucidate the neuroprotective mechanism of [6]-gingerol, we have examined Aβ(25-35)-induced oxidative and/or nitrosative stress and cellular antioxidant defense system against them. [6]-Gingerol effectively suppressed Aβ(25-35)-induced intracellular accumulation of reactive oxygen and/or nitrogen species and restored Aβ(25-35)-depleted endogenous antioxidant glutathione levels. Furthermore, [6]-gingerol treatment up-regulated the mRNA and protein expression of antioxidant enzymes such as γ-glutamylcysteine ligase (GCL) and heme oxygenase-1 (HO-1), the rate limiting enzymes in the glutathione biosynthesis and the degradation of heme, respectively. The expression of aforementioned antioxidant enzymes seemed to be mediated by activation of NF-E2-related factor 2 (Nrf2). These results suggest that [6]-gingerol exhibits preventive and/or therapeutic potential for the management of AD via augmentation of antioxidant capacity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea.

To determine whether aromatherapy can reduce postoperative nausea, the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU. After indicating the severity of nausea on a 100-mm visual analogue scale (VAS), subjects received randomized aromatherapy with isopropyl alcohol, oil of peppermint, or saline (placebo). The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients' nostrils and exhaled slowly through the mouth. Two and 5 minutes later, the subjects rated their nausea on the VAS. Overall nausea scores decreased from 60.6 +/- 4.3 mm (mean +/- SE) before aromatherapy to 43.1 +/- 4.9 mm 2 minutes after aromatherapy (P <.005), and to 28.0 +/- 4.6 mm 5 minutes after aromatherapy (P < 10(-6)). Nausea scores did not differ between the treatments at any time. Only 52% of the patients required conventional intravenous (IV) antiemetic therapy during their PACU stay. Overall satisfaction with postoperative nausea management was 86.9 +/- 4.1 mm and was independent of the treatment group. Aromatherapy effectively reduced the perceived severity of postoperative nausea. The fact that a saline "placebo" was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled.

Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens

Induction of phase 2 detoxication enzymes [e.g., glutathione transferases, epoxide hydrolase, NAD(P)H: quinone reductase, and glucuronosyltransferases] is a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity of electrophiles and reactive forms of oxygen. Since consumption of large quantities of fruit and vegetables is associated with a striking reduction in the risk of developing a variety of malignancies, it is of interest that a number of edible plants contain substantial quantities of compounds that regulate mammalian enzymes of xenobiotic metabolism. Thus, edible plants belonging to the family Cruciferae and genus Brassica (e.g., broccoli and cauliflower) contain substantial quantities of isothiocyanates (mostly in the form of their glucosinolate precursors) some of which (e.g., sulforaphane or 4-methylsulfinylbutyl isothiocyanate) are very potent inducers of phase 2 enzymes. Unexpectedly, 3-day-old sprouts of cultivars of certain crucifers including broccoli and cauliflower contain 10–100 times higher levels of glucoraphanin (the glucosinolate of sulforaphane) than do the corresponding mature plants. Glucosinolates and isothiocyanates can be efficiently extracted from plants, without hydrolysis of glucosinolates by myrosinase, by homogenization in a mixture of equal volumes of dimethyl sulfoxide, dimethylformamide, and acetonitrile at −50°C. Extracts of 3-day-old broccoli sprouts (containing either glucoraphanin or sulforaphane as the principal enzyme inducer) were highly effective in reducing the incidence, multiplicity, and rate of development of mammary tumors in dimethylbenz(a)anthracene-treated rats. Notably, sprouts of many broccoli cultivars contain negligible quantities of indole glucosinolates, which predominate in the mature vegetable and may give rise to degradation products (e.g., indole-3-carbinol) that can enhance tumorigenesis. Hence, small quantities of crucifer sprouts may protect against the risk of cancer as effectively as much larger quantities of mature vegetables of the same variety.

The effect of inhaling peppermint odor and ethanol in women athletes.

The purpose of this study was to determine whether inhaling peppermint odor has effects on time of running, maximum heart rate (MHR), maximum oxygen consumption (VO2max), oxygen consumption (VO2), minute ventilation (VE) and respiratory exchange ratio (RER) during acute intensive exercise or not. 36 women soccer player were chosen for participating in this research. They were randomly divided in 3 groups (control, inhaling peppermint, inhaling mixture of peppermint and ethanol). In order to be aware of similarity of groups, the subjects' BMI was determined and ANOVA did not show any significant differences (p < 0.05). The subjects of three groups ran on treadmill according to Bruce test. Heart rate, time of running, VO2max, VO2, VE and RER were measured by Gas Analyzer. After collecting the data, ANOVA was done (p < 0.05) and the results showed that in this study the inhaling of fragrant odors did not have any significant effect on the time of running, MHR, VO2max, VO2, VE and RER, which we think is due to the intensity and duration of training. Referring to our results of the present study; we suggest that inhaling peppermint odor during acute intensive exercise has no significant effect on pulmonary indexes and physical performance (Tab. 4, Fig. 1, Ref. 21).

Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic.

Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of IP6 was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.

Berry fruits for cancer prevention: current status and future prospects.

Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of "whole berries" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.

Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological activities of lavender essential oil.

Essential oils distilled from members of the genus Lavandula have been used both cosmetically and therapeutically for centuries with the most commonly used species being L. angustifolia, L. latifolia, L. stoechas and L. x intermedia. Although there is considerable anecdotal information about the biological activity of these oils much of this has not been substantiated by scientific or clinical evidence. Among the claims made for lavender oil are that is it antibacterial, antifungal, carminative (smooth muscle relaxing), sedative, antidepressive and effective for burns and insect bites. In this review we detail the current state of knowledge about the effect of lavender oils on psychological and physiological parameters and its use as an antimicrobial agent. Although the data are still inconclusive and often controversial, there does seem to be both scientific and clinical data that support the traditional uses of lavender. However, methodological and oil identification problems have severely hampered the evaluation of the therapeutic significance of much of the research on Lavandula spp. These issues need to be resolved before we have a true picture of the biological activities of lavender essential oil. Copyright 2002 John Wiley & Sons, Ltd.

Sporamin induce apoptosis in human tongue carcinoma cells by down-regulating Akt/GSK-3 signaling.

We investigated the effects of sporamin, the major soluble protein with a kunitz-type trypsin inhibitory activity in the root tuber of the sweet potato, on cell proliferation, apoptosis, Akt/GSK-3 signaling and its related genes to provide more insights in the mechanism behind the inhibitory effects of sporamin in a human tongue cancer line Tca8113. In this study, sporamin inhibited cell proliferation and induced apoptosis in Tca8113 cells in a concentration-dependent and time-dependent manner. Consistently, Bax was up-regulated and Bcl-2 was down-regulated in sporamin-treated cells. Furthermore, Akt/GSK-3 signaling was down-regulated in sporamin-treated cells. Consistently, the phosphorylated Bad was significantly declined in sporamin-treated Tca8113 cells. These results suggest the antiproliferative effects of sporamin in Tca8113 cells might result partly from induction of apoptosis by down-regulating Akt/GSK-3 pathway. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Absence of pomegranate ellagitannins in the majority of commercial Pomegranate extracts: implications for standardization and quality control.

The health benefits associated with pomegranate juice have led to the development of pomegranate extracts as botanical dietary supplements. Pomegranates contain hydrolyzable tannins in the form of punicalagins and punicalin as well as tannin-based complex oligomers that account for much of the antioxidant activity in juice. The content of ellagic acid has been used to standardize most pomegranate extract dietary supplements marketed. However, supplements can be adulterated with ellagic acid from less expensive plant sources and undercut this method of standardization. To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity. Future research is needed to assess the health impact of substituting ellagic acid for the complex mix of phytochemicals in a pomegranate extract dietary supplement.

Black pepper and its pungent principle-piperine: a review of diverse physiological effects.

Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.

Genetic Analysis of Chemosensory Traits in Human Twins

We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.

Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis

Objective To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane controlled trials register up to April 2008. Review methods Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. Results 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients (0.43, 0.32 to 0.59). Conclusion Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome.

Antiallergic activities of pigmented rice bran extracts in cell assays.

Using a panel of chemical, biochemical, and cell assays, we determined inhibitory effects of extracts of the pigmented black rice brans on in vitro allergic reactions. Ethanol-water (70% v/v) extracts from 5 pigmented brans were found to be more effective than an extract from a nonpigmented rice cultivar in suppressing the release of histamine and beta-hexosaminidase from basophilic RBL-2H3 cells stimulated with both Ionophore A23187 and immunoglobulin E (IgE)-antigen complexes. Suppression was also obtained with A23187-stimulated rat peritoneal mast cells. The extent of inhibition of these 2 markers of the immune response was accompanied by an influx of calcium ions. The inhibition of the immune process by the pigmented brans was confirmed by the observed modulation of the proinflammatory cytokine gene expressions and cytokine release, as indicated by the reduction in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-4, and IL-6 mRNA expressions determined with the reverse transcription-polymerase chain reaction (RT-PCR). Reduction of TNF-alpha, IL-1beta, and IL-6 protein release from both the cultured cell line and peritoneal cells was further confirmed by enzyme-linked immunoadsorbent assays. Rice bran from the LK1-3-6-12-1-1 cultivar was the most effective inhibitor in all assays. This particular rice variety merits further evaluation as part of a human diet to ascertain its potential to protect against allergic diseases such as hay fever and asthma.

Phenolic substance characterization and chemical and cell-based antioxidant activities of 11 lentils grown in the northern United States.

Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil cultivars grown in the cool northern parts of the United States were investigated. Individual phenolic compounds, including phenolic acids, flavan-3-ols, flavones, and anthocyanins, were further quantitatively investigated by HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton exhibited the highest individual flavan-3-ols (catechin and epicatechin) and total flavonoids, as well as the highest antioxidant properties (PRSC and CAA) among all lentils tested. Five phenolic acids of the benzoic types and their derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one flavone (luteolin) were detected in all lentil cultivars. Among all phenolic compounds detected, sinapic acid was the predominant phenolic acid, and (+)-catechin and (-)-epicatechin were the predominant flavonoids. These results showed that different phenotype lentils possessed considerable variations in their individual phenolic compounds, as well as chemical and cellular antioxidant activities. Caffeic acid, catechin, epicatechin, and total flavonoids significantly (p < 0.05) correlated with peroxyl radical scavenging assay. Cellular antioxidant assay significantly correlated with chemical antioxidant assay ORAC. The results from this study could be very interesting for breeding programs to improve lentils for use as functional foods.

Fresh aromatic herbs containing methylchavicol did not exhibit the pro-oxidative effects of pure methylchavicol on a human hepatoma cell line, HepG2.

Methylchavicol (CH(3)-CV), an important aromatic constituent of different plants like tarragon and basils, has been shown to be carcinogenic by a mechanism yet unclear, although it has been reported that carcinogenicity of CH(3)-CV in rodent might be linked to its metabolic conversion into a genotoxic electrophilic metabolite generated through a two steps bioactivation pathway catalyzed by cytochrome P450 enzymes and sulfotransferases. The induction of carcinogenesis by certain agents has been associated with the generation of oxidative stress. The aim of the present study was to determine whether pure methylchavicol applied on a human hepatoma cell line, HepG2, could promote oxidative stress and might alter the expression of procarcinogenic biomarkers such as the drug-metabolizing enzyme (CYP2E1), the inducible form of nitric oxide synthase (iNOS) and might induce the expression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Mn-SOD that control the redox equilibrium of the cells. CH(3)-CV was shown to cause a significant induction of oxidative stress, as revealed by luminol-dependent chemiluminescence (LDCL) and to alter dramatically the expression of CYP2E1, iNOS and Mn-SOD, indicating that the toxic effect of CH(3)-CV could be mediated through a nitric oxide dependent mechanism. Under similar experimental conditions, the extracts from tarragon, chervil and basil did not induce such biological changes. These results provide evidence that the generation of an oxidative stress may be a significant event occurring during CH(3)-CV-induced toxicity. It also suggests that natural extracts containing different amounts of CH(3)-CV (tarragon, chervil and basil) did not elicit such toxicity and might contain compounds able to counteract this detrimental property. Copyright © 2012. Published by Elsevier Masson SAS.

Antiproliferation and induction of apoptosis by Moringa oleifera leaf extract on human cancer cells.

Medicinal plants provide an inexhaustible source of anticancer drugs in terms of both variety and mechanism of action. Induction of apoptosis is the key success of plant products as anticancer agents. The present study was designed to determine the antiproliferative and apoptotic events of Moringa oleifera leaf extract (MLE) using human tumor (KB) cell line as a model system. KB cells were cultured in the presence of leaf extracts at various concentrations for 48 h and the percentage of cell viability was evaluated by MTT assay. MLE showed a dose-dependent inhibition of cell proliferation of KB cells. The antiproliferative effect of MLE was also associated with induction of apoptosis as well as morphological changes and DNA fragmentation. The morphology of apoptotic nuclei was quantified using DAPI and propidium iodide staining. The degree of DNA fragmentation was analyzed using agarose gel electrophoresis. In addition, MLE at various concentrations was found to induce ROS production suggesting modulation of redox-sensitive mechanism. Eventually, HPTLC analysis indicated the presence of phenolics such as quercetin and kaempferol. Thus, these findings suggest that the leaf extracts from M. oleifera had strong antiproliferation and potent induction of apoptosis. Thus, it indicates that M. oleifera leaf extracts has potential for cancer chemoprevention and can be claimed as a therapeutic target for cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Watermelon consumption increases plasma arginine concentrations in adults.

OBJECTIVE: Watermelon is a rich source of citrulline, an amino acid that can be metabolized to arginine, a conditionally essential amino acid for humans. Arginine is the nitrogenous substrate used in the synthesis of nitric oxide and plays an essential role in cardiovascular and immune functions. No detailed studies have been conducted to evaluate plasma arginine response in humans after long-term feeding of citrulline from natural plant sources. This study investigated if watermelon juice consumption increases fasting concentrations of plasma arginine, ornithine, and citrulline in healthy adult humans. METHODS: Subjects (n = 12-23/treatment) consumed a controlled diet and 0 (control), 780, or 1560 g of watermelon juice per day for 3 wk in a crossover design. The treatments provided 1 and 2 g of citrulline per day. Treatment periods were preceded by washout periods of 2 to 4 wk. RESULTS: Compared with the baseline, fasting plasma arginine concentrations increased 12% after 3 wk of the lower-dose watermelon treatment; arginine and ornithine concentrations increased 22% and 18%, respectively, after 3 wk of the higher-dose watermelon treatment. Fasting citrulline concentrations did not increase relative to the control but remained stable throughout the study. CONCLUSION: The increased fasting plasma concentrations of arginine and ornithine and stable concentrations of plasma citrulline in response to watermelon juice consumption indicated that the citrulline from this plant origin was effectively converted into arginine. These results demonstrate that plasma concentration of arginine can be increased through intake of citrulline from watermelon.

Sirtuins in cognitive ageing and Alzheimer's disease.

PURPOSE OF REVIEW: Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology. RECENT FINDINGS: Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD(+). Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling. SUMMARY: Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1.

Antimutagenic effect of broccoli flower head by the ames salmonella reverse mutation assay.

A study was performed to investigate the antimutagenic effect of broccoli flower head by the Ames Salmonella reverse mutation assay. Broccoli flower head being the most highly edible part in the plant was analysed for its antimutagenic effect. Without isolating the phytomolecules, the crude ethanol extract of broccoli flower head was tested for suppressing the mutagenic effect induced by certain chemical mutagens. Three strains - TA 98, TA102 and TA 1535 were used in the study. The tester strains were challenged with their respective mutagens. These were challenged with the ethanol extract of broccoli flower head at concentrations of 23 and 46 mg/plate. The plates were incubated for 72 h and the revertant colonies were counted. The crude extract did not prove to be promutagenic. The ethanol extract of the broccoli flower head at 46 mg/plate suppressed the mutagenic effect induced by the corresponding positive mutagens on all the three tester strains used in this study. The crude extract of broccoli flower head alone was not cytotoxic even at the maximum concentration tested (46 mg/plate). In conclusion, the ethanol extract of broccoli at 46 mg/plate suggests their diverse antimutagenic potential against the mutagenic chemicals employed in this study. (c) 2007 John Wiley & Sons, Ltd.

Colloidal oatmeal: history, chemistry and clinical properties.

Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.

A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders.

Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the 'Mediterranean diet', and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.

Dietary correlates of urinary 6-sulfatoxymelatonin concentrations in the Nurses' Health Study cohorts

Background: Age and certain lifestyle factors, including a higher body mass index and exposure to light at night, are related to lower circulating concentrations of melatonin—a hormone with probable cancer-protective properties. Although melatonin is a direct derivative of the essential amino acid tryptophan, little is known about the relation of diet with melatonin concentrations. Objective: The objective was to examine cross-sectional associations of various nutrients and dietary factors as well as food groups with creatinine-adjusted first morning urinary melatonin (6-sulfatoxymelatonin; aMT6s) concentrations. Design: Participants were 998 healthy women from 2 independent cohorts: the Nurses' Health Study (NHS; n = 585) and NHS II (n = 413). We computed least-squares mean hormone concentrations across categories of dietary variables, with adjustment for total energy intake, age, and other nondietary factors known to be associated with aMT6s concentrations. Results: In multivariate analyses, we found no significant associations between the intake of various nutrients, including tryptophan and urinary melatonin concentrations. A higher intake of meat, particularly red meat, was associated with lower concentrations of aMT6s (adjusted mean concentrations of aMT6s across increasing quartiles of red meat intake were 17.9, 17.0, 18.1, and 15.3 ng/mg creatinine; P for trend = 0.02). In contrast, neither poultry intake (including turkey) nor fish intake was associated with aMT6s concentrations. Conclusion: Although no specific nutrients were associated with altered concentrations of melatonin, our findings raise the possibility that several specific foods, including red meat, could affect cancer risk through the lowering of melatonin concentrations.

Medication management of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. SUMMARY: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966. © 2014 S. Karger AG, Basel.

Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition.

The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.

Inositol Hexakisphosphate Inhibits Osteoclastogenesis on RAW 264.7 Cells and Human Primary Osteoclasts

Background Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. Methodology/Principal Findings The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of bone resorption activity and TRAP mRNA levels was found. On the other hand, we show that 1 µM of IP6 inhibits osteoclastogenesis of human peripheral blood mononuclear cells (PBMNC) and their resorption activity both, when given to undifferentiated and to mature osteoclasts. Conclusions/Significance Our results demonstrate that IP6 inhibits osteoclastogenesis on human PBMNC and on the RAW264.7 cell line. Thus, IP6 may represent a novel type of selective inhibitor of osteoclasts and prove useful for the treatment of osteoporosis.

Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts.

Twenty-four plant lignans were analyzed by high-performance liquid chromatography-tandem mass spectrometry in bran extracts of 16 cereal species, in four nut species, and in two oilseed species (sesame seeds and linseeds). Eighteen of these were lignans previously unidentified in these species, and of these, 16 were identified in the analyzed samples. Four different extraction methods were applied as follows: alkaline extraction, mild acid extraction, a combination of alkaline and mild acid extraction, or accelerated solvent extraction. The extraction method was of great importance for the lignan yield. 7-Hydroxymatairesinol, which has not previously been detected in cereals because of destructive extraction methods, was the dominant lignan in wheat, triticale, oat, barley, millet, corn bran, and amaranth whole grain. Syringaresinol was the other dominant cereal lignan. Wheat and rye bran had the highest lignan content of all cereals; however, linseeds and sesame seeds were by far the most lignan-rich of the studied species.

Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells.

Chamomile (Matricaria chamomilla), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7-O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.

Erythritol is a sweet antioxidant.

OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.

Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin.

The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.

Effects of tomato extract on human platelet aggregation in vitro.

Among all fruits tested in vitro for their anti-platelet property, tomato had the highest activity followed by grapefruit, melon, and strawberry, whereas pear and apple had little or no activity. Tomato extract (20-50 microl of 100% juice) inhibited both ADP- and collagen-induced aggregation by up to 70% but could not inhibit arachidonic acid-induced platelet aggregation and concomitant thromboxane synthesis under similar experimental conditions. The anti-platelet components (MW <1000 Da) in tomatoes are water soluble, heat stable and are concentrated in the yellow fluid around the seeds. The active fractions were separated using gel filtration and HPLC. The aqueous fraction (110 000 xg supernatant) of tomatoes containing anti-platelet activity was subjected to gel filtration column chromatography (Biogel P2 column). The activity was fractionated into two peaks, peak-3 and peak-4 (major peak). Subsequently, peak-4 was further purified by HPLC using a reversed-phase column. NMR and mass spectroscopy studies indicated that peak F2 (obtained from peak 4) contained adenosine and cytidine. Deamination of peak F2 with adenosine deaminase almost completely abolished its anti-platelet activity, confirming the presence of adenosine in this fraction. In comparison, deamination of peak-4 resulted in only partial loss of inhibitory activity while the activity of peak-3 remained unaffected. These results indicate that tomatoes contain anti-platelet compounds in addition to adenosine. Unlike aspirin, the tomato-derived compounds inhibit thrombin-induced platelet aggregation. All these data indicate that tomato contains very potent anti-platelet components, and consuming tomatoes might be beneficial both as a preventive and therapeutic regime for cardiovascular disease.

Simultaneous analysis of serotonin, melatonin, piceid and resveratrol in fruits using liquid chromatography tandem mass spectrometry.

An analytical method was developed for the simultaneous quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol using reversed-phase high performance liquid chromatography coupled to mass spectrometry (HPLC-MS) with electrospray ionization (ESI) in both positive and negative ionization modes. HPLC optimal analytical separation was achieved using a mixture of acetonitrile and water with 0.1% formic acid as the mobile phase in linear gradient elution. The mass spectrometry parameters were optimized for reliable quantification and the enhanced selectivity and sensitivity selected reaction monitoring mode (SRM) was applied. For extraction, the direct analysis of initial methanol extracts was compared with further ethyl acetate extraction. In order to demonstrate the applicability of this analytical method, serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol from 24 kinds of commonly consumed fruits were quantified. The highest serotonin content was found in plantain, while orange bell peppers had the highest melatonin content. Grape samples possessed higher trans- and cis-piceid, and trans- and cis-resveratrol contents than the other fruits. The results indicate that the combination of HPLC-MS detection and simple sample preparation allows the rapid and accurate quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol in fruits. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular mechanisms of curcumin action: gene expression.

Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas.

Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages.

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.

Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements.

BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations <147 pmol/l (200 pg/ml). 37 subjects (76%) had serum B12 concentrations <221 pmol/l (300 pg/ml). 23 subjects (47%) had abnormal urinary MMA concentrations above or equal to 4.0 microg/mg creatinine. Sublingual cyanocobalamin and nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p < 0.01; yeast p < 0.05, probiotic > 0.20). CONCLUSIONS: The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.

Protection against cancer by dietary IP6 and inositol.

Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.

Radioprotection by plant products: present status and future prospects.

The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.

Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial

Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total cancer among 1,312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56–0.96; P=0.022), but this did not differ significantly from that among 13,329 men initially free of cancer (HR, 0.94; 95% CI, 0.87–1.02; P=0.15) (P, interaction = 0.07). Conclusions In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.

Species identification and vitamin A level in lutjanid fish implicated in vitamin A poisoning.

One outbreak of food poisoning associated with ingestion of the liver of a large lutjanid fish was investigated in this study. The symptoms in three patients primarily included headache, nausea, vomiting, fever, vertigo, and visual disorientation and later included peeling of the skin. The species of fish implicated in this incident was Etelis carbunculus (family Lutjanidae) as determined by direct sequence analysis and PCR plus restriction fragment length polymorphism analysis for detection of the cytochrome b gene. Subsequently, several specimens of E. carbunculus of different body weights were collected, and the level of vitamin A in the muscle and liver was determined by high-performance liquid chromatography. The average level of vitamin A in E. carbunculus muscle was 12 +/- 2 IU/g and that in the liver was 9,844 +/- 7,812 IU/g. Regression models indicate that E. carbunculus with higher body weight and liver weight will have higher levels of vitamin A levels in the liver.

Plant foods and brain aging: a critical appraisal.

In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

Effects of baking and boiling on the nutritional and antioxidant properties of sweet potato [Ipomoea batatas (L.) Lam.] cultivars.

The effects of baking and boiling on the nutritional and antioxidant properties of three sweet potato cultivars (Beniazuma, Koganesengan, Kotobuki) cultivated in Turkey were investigated. The samples were analyzed for proximate composition, total phenolic content, ascorbic acid, β-carotene, antiradical activity, and free sugars. The dry matter, protein, and starch contents of the sweet potatoes were significantly changed by the treatments while the ash and crude fiber contents did not differ as significantly. The β-carotene contents of baked and boiled sweet potatoes were lower than those of fresh sweet potatoes; however, the total phenolic and ascorbic acid contents of the baked and boiled sweet potatoes were higher than those of the fresh samples. Generally, the antiradical activity of the sweet potatoes increased with the treatments. Sucrose, glucose, and fructose were quantified as free sugars in all fresh sweet potatoes; however, maltose was determined in the treated samples. In terms of the analyzed parameters, there were no explicit differences among the sweet potato cultivars.

Anti-proliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae.

Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti-proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti-proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer.

Bitter melon (Momordica charantia) extract suppresses adrenocortical cancer cell proliferation through modulation of the apoptotic pathway, steroid...

Adrenocortical carcinomas are rare but present with extremely poor prognosis. One of the approaches to control cancer progression and reduce cancer risk is prevention through diet. Bitter melon is widely consumed as a vegetable and especially as a traditional medicine in many countries. In this study, we have used human and mouse adrenocortical cancer cells as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. The protein concentrations of BME and other extracts were measured before use. First, BME treatment of adrenocortical cancer cells resulted in a significantly dose-dependent decrease in cell proliferation. However, we did not observe an antiproliferative effect in adrenocortical cancer cells treated with extracts from blueberry, zucchini, and acorn squash. Second, apoptosis of adrenocortical cancer cells was accompanied by increased caspase-3 activation and poly(ADP-ribose) polymerase cleavage. BME treatment enhanced cellular tumor antigen p53, cyclin-dependent kinase inhibitor 1A (also called p21), and cyclic AMP-dependent transcription factor-3 levels and inhibited G1/S-specific cyclin D1, D2, and D3, and mitogen-activated protein kinase 8 (also called Janus kinase) expression, suggesting an additional mechanism involving cell cycle regulation and cell survival. Third, BME treatment decreased the key proteins involved in steroidogenesis in adrenocortical cancer cells. BME treatment decreased the level of phosphorylation of cyclin-dependent kinase 7, which is required, at least in part, for steroidogenic factor 1 activation. Finally, we observed that BME treatment significantly reduced the level of insulin-like growth factor 1 receptor and its downstream signaling pathway as evidenced by lower levels of phosphorylated RAC-α serine/threonine-protein kinase. Taken together, these data illustrate the inhibitory effect of bitter melon on cell proliferation of adrenocortical cancer through modulation of diverse mechanisms.

Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.

OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.

Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial

Context Though multivitamins aim to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies examining regular multivitamin use have been inconsistently associated with CVD, with no long-term clinical trials of multivitamin use. Objective To determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. Design The Physicians' Health Study II is a randomized, double-blind, placebo-controlled trial of a common daily multivitamin, that began in 1997 with continued treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures The primary cardiovascular outcome was a composite endpoint of major cardiovascular events, including nonfatal myocardial infarction (MI), nonfatal stroke, and fatal CVD. Secondary outcomes included MI and stroke individually. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 1,732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (active and placebo multivitamin groups, 11.0 and 10.8 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.91–1.10; P=0.91). Further, a daily multivitamin had no effect on total MI (active and placebo multivitamin groups, 3.9 and 4.2 events per 1,000 person-years; HR, 0.93; 95% CI, 0.80–1.09; P=0.39), total stroke (active and placebo multivitamin groups, 4.1 and 3.9 events per 1,000 person-years; HR, 1.06; 95% CI, 0.91–1.23; P=0.48), or cardiovascular mortality (active and placebo multivitamin groups, 5.0 and 5.1 events per 1,000 person-years; HR, 0.95; 95% CI, 0.83–1.09; P=0.47). A daily multivitamin was also not significantly associated with total mortality (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P, interaction = 0.62). Conclusions A daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.

Immunity: plants as effective mediators.

In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.

Curcumin: getting back to the roots.

The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."

Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity.

BACKGROUND/AIMS: Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. METHODS: In 2004, identification of four index cases of acute hepatitis associated with Herbalife intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife products were investigated. RESULTS: Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. Three patients resumed consumption of Herbalife products following normalization of liver enzymes, resulting in a second bout of hepatitis. CONCLUSIONS: An association between intake of Herbalife products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease.

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-gallate [EGCG]) delivered in a form of ointment or capsule in patients with human papilloma virus (HPV) infected cervical lesions. Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients (74%) under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response, and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10 patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate (35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39) in untreated controls (P<0.05). Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.

Acute and Sub-Acute Toxicological Assessment of the Aqueous Seed Extract of Persea Americana Mill (Lauraceae) in Rats

The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

Prostate cancer and inositol hexaphosphate: efficacy and mechanisms.

There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.

Vomiting from multivitamins: a potential drug interaction.

A commercial weight loss program with a client base composed of >95% women experienced sporadic complaints of nausea and vomiting after changing its multivitamin supplier. This retrospective and observational study was designed to determine if related adverse event reports were significant, and to investigate potential mechanism for their occurrence in this group of subjects, many of whom were concurrently receiving oral contraceptives or hormone replacement therapy. Incidence of nausea, vomiting, rash, and total complaints in the 3 months following the change of the multivitamin formulation was compared with the same complaints in the 3 months before the change. In the 3 months following the multivitamin change, there were 166 complaints of nausea and vomiting, 9 complaints of rash and 194 total complaints from a group of 88,468 patients. In the 3 months before the change in the multivitamin, there had been 2 complaints of nausea and vomiting, no complaints of rash, and 11 total complaints from 88,252 patients. The difference detected by a chi-squared test was significant for all events studied; nausea and vomiting (P < 0.0001), rash (P < 0.02), and total complaints (P < 0.0001). The altered multivitamins contained added citrus bioflavanoids not included in the original formula. Citrus bioflavanoids decrease the clearance of exogenous estrogens by inhibiting cytochrome P450 enzyme systems. Elevated estrogen levels could account for the increased incidence of nausea and vomiting. This experience demonstrates that adding dietary herbal supplements to multivitamins may be associated with adverse interactions with prescription drugs.

Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations.

Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. In view of WHO guidelines, single herbal drugs used in herbal formulations were collected from local market, for testing heavy metals and persistent pesticides residue. Therefore, in the present case, we have examined few local samples of certain herbs viz. Emblica officinalis, Terminalia chebula, Terminalia belerica, and Withania somnifera. The present studies were selected for estimation of four heavy metals namely Arsenic, Cadmium, Lead, and Mercury. Apart from these, pesticide residue Viz. Organochlorine pesticides, Organophosphorus pesticides, and Pyrethroids were analyzed in the four samples of single crude drugs. Heavy metals and pesticide residue were found below detection limits in all the samples.

Variations in product choices of frequently purchased herbs: caveat emptor.

BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.

Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro.

Polyphenol-rich berry extracts were screened for their antiproliferative effectiveness using human cervical cancer (HeLa) cells grown in microtiter plates. Rowan berry, raspberry, lingonberry, cloudberry, arctic bramble, and strawberry extracts were effective but blueberry, sea buckthorn, and pomegranate extracts were considerably less effective. The most effective extracts (strawberry > arctic bramble > cloudberry > lingonberry) gave EC 50 values in the range of 25-40 microg/(mL of phenols). These extracts were also effective against human colon cancer (CaCo-2) cells, which were generally more sensitive at low concentrations but conversely less sensitive at higher concentrations. The strawberry, cloudberry, arctic bramble, and the raspberry extracts share common polyphenol constituents, especially the ellagitannins, which have been shown to be effective antiproliferative agents. However, the components underlying the effectiveness of the lingonberry extracts are not known. The lingonberry extracts were fractionated into anthocyanin-rich and tannin-rich fractions by chromatography on Sephadex LH-20. The anthocyanin-rich fraction was considerably less effective than the original extract, whereas the antiproliferative activity was retained in the tannin-rich fraction. The polyphenolic composition of the lingonberry extract was assessed by liquid chromatography-mass spectrometry and was similar to previous reports. The tannin-rich fraction was almost entirely composed of procyanidins of linkage type A and B. Therefore, the antiproliferative activity of lingonberry was caused predominantly by procyanidins.

Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells.

Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.

Lignans in man and in animal species.

In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.

The comet assay with 8 mouse organs: results with 39 currently used food additives.

We determined the genotoxicity of 39 chemicals currently in use as food additives. They fell into six categories-dyes, color fixatives and preservatives, preservatives, antioxidants, fungicides, and sweeteners. We tested groups of four male ddY mice once orally with each additive at up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow 3 and 24h after treatment. Of all the additives, dyes were the most genotoxic. Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and Rose Bengal induced dose-related DNA damage in the glandular stomach, colon, and/or urinary bladder. All seven dyes induced DNA damage in the gastrointestinal organs at a low dose (10 or 100mg/kg). Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced DNA damage in the colon at close to the acceptable daily intakes (ADIs). Two antioxidants (butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)), three fungicides (biphenyl, sodium o-phenylphenol, and thiabendazole), and four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA damage in gastrointestinal organs. Based on these results, we believe that more extensive assessment of food additives in current use is warranted.

Organochlorine pesticide residues in bamboo shoot.

BACKGROUND: Xenobiotic organochlorine pesticides (OCPs) are a major environmental problem because of their historic widespread use, pronounced persistence against chemical and biological degradation, and bioaccumulation in the food chain. Pesticide use is prevalent in the production of edible bamboo shoots, which are exported widely from China. To evaluate the quality of Chinese bamboo shoots we determined the residual content of some OCPs in shoot samples. RESULTS: Three types of OCPs-hexachlorocyclohexane (HCH), 1,1,1-trichlor-2,2-bis(p-chlorophenyl)ethane (DDT) and pentachloronitrobenzene (PCNB)-were detected in bamboo shoots from Zhejiang province, China. Detection rates were 100%, 100% and 75% for HCH, DDT and PCNB, respectively. However, the average residue concentration did not exceed the maximum residue limit for pesticides detected in food in China (50 µg kg(-1) ). In terms of residue concentrations of the pesticides, 82.14% of the bamboo shoot samples could be classified as safe. CONCLUSION: While all sampled bamboo shoots contained OCP, most (82.14%) were safe for consumption. 2010 Society of Chemical Industry.

Goji berry effects on macular characteristics and plasma antioxidant levels.

PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.

Comparative flavonoids contents of selected herbs and associations of their radical scavenging activity with antiproliferative actions in V79-4 cells.

To elucidate the health benefit of herbal teas on the cytotoxicity induced by H(2)O(2) in V79-4 cells, herbal extracts and its flavonoids were tested using lactate dehydrogenase release and determining intracellular reactive oxygen species generation and antioxidant activity with superoxide radical scavenging assay. Significant decrease in cell viability was observed on V79-4 cells treated with H(2)O(2) (1 mM), while herbal extracts and its flavonoids including catechin and epigallocatechin gallate prevented the LDH release from H(2)O(2) cytotoxicity. Total catechin contents of green tea (65.6 mg/g of dry matter) were significantly higher than other herbal teas (35.8 to 1.2 mg/g of DM). The relative concentration of the 4 major tea catechins ranked EGCG > EGC > EC > C. Green tea exhibited the lowest IC(50) values (2 g fresh herb/100 mL) of superoxide radical scavenging activity among the tested herbal tea, which indicates powerful antioxidant activity in O(2)(*-) radicals scavenging, followed by black tea, dandelion, hawthorn, rose hip, chamomile.

Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms.

The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.

Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer.

Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.

Updates on human papillomavirus and genital warts and counseling messages from the 2010 Sexually Transmitted Diseases Treatment Guidelines.

BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.

Micronutrients intake is associated with improved sperm DNA quality in older men.

OBJECTIVE: To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men. DESIGN: Cross-sectional study design with equalized assignments into age groups. SETTING: National laboratory and university. PATIENT(S): Nonclinical group of 22-80-year-old nonsmoking men (n = 80) who reported no fertility problems. MAIN OUTCOME MEASURE(S): Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay). RESULT(S): Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed. CONCLUSION(S): Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage. Copyright © 2012. Published by Elsevier Inc.

Dietary suppression of colonic cancer. Fiber or phytate?

The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.

Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.

The use of substances as the substrate for atrial fibrillation is not frequently recognized. Chocolate is derived from the roasted seeds of the plant theobroma cacao and its components are the methylxanthine alkaloids theobromine and caffeine. Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Normal consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Sympathomimetic effects, due to circulating catecholamines cause the cardiac manifestations of caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with coronary artery disease and clinically stable asthma or chronic obstructive pulmonary disease. Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. We present a case of atrial fibrillation associated with chocolate intake abuse in a 19-year-old Italian woman with chronic salbutamol inhalation abuse. This case focuses attention on chocolate intake abuse associated with chronic salbutamol abuse as the substrate for atrial fibrillation. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.

BACKGROUND: Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires. METHODS: A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction. RESULTS: Our analyses indicated a significantly higher rate of total and specific treatment-emergent SD and specific phases of dysfunction compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone. DISCUSSION: Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.

Cranberry and blueberry: evidence for protective effects against cancer and vascular diseases.

Growing evidence from tissue culture, animal, and clinical models suggests that the flavonoid-rich fruits of the North American cranberry and blueberry (Vaccinium spp.) have the potential ability to limit the development and severity of certain cancers and vascular diseases including atherosclerosis, ischemic stroke, and neurodegenerative diseases of aging. The fruits contain a variety of phytochemicals that could contribute to these protective effects, including flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its esters. Cranberry and blueberry constituents are likely to act by mechanisms that counteract oxidative stress, decrease inflammation, and modulate macromolecular interactions and expression of genes associated with disease processes. The evidence suggests a potential role for dietary cranberry and blueberry in the prevention of cancer and vascular diseases, justifying further research to determine how the bioavailability and metabolism of berry phytonutrients influence their activity in vivo.

Triphala, Ayurvedic formulation for treating and preventing cancer: a review.

BACKGROUND: Triphala (Sanskrit tri = three and phala = fruits), composed of the three medicinal fruits Phyllanthus emblica L. or Emblica officinalis Gaertn., Terminalia chebula Retz., and Terminalia belerica Retz. is an important herbal preparation in the traditional Indian system of medicine, Ayurveda. Triphala is an antioxidant-rich herbal formulation and possesses diverse beneficial properties. It is a widely prescribed Ayurvedic drug and is used as a colon cleanser, digestive, diuretic, and laxative. Cancer is a major cause of death, and globally studies are being conducted to prevent cancer or to develop effective nontoxic therapeutic agents. Experimental studies in the past decade have shown that Triphala is useful in the prevention of cancer and that it also possesses antineoplastic, radioprotective and chemoprotective effects. CONCLUSIONS: This review for the first time summarizes these results, with emphasis on published observations. Furthermore, the possible mechanisms responsible for the beneficial effects and lacunas in the existing knowledge that need to be bridged are also discussed.

Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials

Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.

Safety considerations and potential interactions of vitamins: should vitamins be considered drugs?

OBJECTIVE: To examine adverse effects, adverse events, and potential interactions of vitamins in light of their current prevalence of use, and to discuss whether vitamins should be considered over-the-counter drugs or natural health products/dietary supplements. DATA SOURCES: We performed a MEDLINE/PubMed search, explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine Comprehensive Database, and the database of the University of Maryland), and examined reference lists of included studies published from 1966 through October 2009. STUDY SELECTION AND DATA EXTRACTION: The studies were reviewed, with an emphasis on randomized controlled clinical trials. We included articles with the most clinically important information with regard to adverse events and interactions. DATA SYNTHESIS: Vitamins are used by over one third of the North American population. Vitamins have documented adverse effects and toxicities, and most have documented interactions with drugs. While some vitamins (biotin, pantothenic acid, riboflavin, thiamine, vitamin B(12), vitamin K) have minor and reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can cause serious adverse events. Two water-soluble vitamins, folic acid and niacin, can also have significant toxicities and adverse events. CONCLUSIONS: Our recommendation is that vitamins A, E, D, folic acid, and niacin should be categorized as over-the-counter medications. Labeling of vitamins, especially those intended for children and other vulnerable groups, should include information on possible toxicities, dosing, recommended upper intake limits, and concurrent use with other products. Vitamin A should be excluded from multivitamin supplements and food fortificants.

Cataract is a self-defence reaction to protect the retina from oxidative damage.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.