***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents . The hypothesis was tested that , in healthy humans , p.o . administration of resveratrol is safe and results in measurable plasma levels of resveratrol . A phase I study of oral resveratrol ( single doses of 0.5 , 1 , 2.5 , or 5 g ) was conducted in 10 healthy volunteers per dose level .  Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-t and em mass spectrometry and quantitated by high-performance liquid chromatography-UV . Consumption of resveratrol did not cause serious adverse events . Resveratrol and six metabolites were recovered from plasma and urine . Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL ( 2.4 μmol/L , mean ± SD ; n = 10 ) , which occurred 1.5 h post-dose . Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher . The area under the plasma concentration curve ( AUC ) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol . Urinary excretion of resveratrol and its metabolites was rapid , with 77 % of all urinary agent-derived species excreted within 4 h after the lowest dose . Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy . However , the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52 Background Ginsenosides , the major bioactive compounds in ginseng root , have been found to have antioxidant , immunomodulatory and anti-inflammatory activities . This study investigated the effects of ginsenosides on carbon tetrachloride (CCl4)-induced hepatitis and liver fibrosis in rats . Methods Male Sprague – Dawley rats were r and omly divided into four groups : control , CCl4 , CCl4 + 0.5 g/kg Panax ginseng extract and CCl4 + 0.05 g/kg ginsenoside Rb1 groups . The treated groups were orally given Panax ginseng extract or ginsenoside Rb1 two weeks before the induction of liver injury for successive 9 weeks . Liver injury was induced by intraperitoneally injected with 400 ml/l CCl4 at a dose of 0.75 ml/kg body weight weekly for 7 weeks . The control group was intraperitoneally injected with olive oil . Results The pathological results showed that ginsenoside Rb1  decreased hepatic fat deposition ( 2.65 ± 0.82 vs 3.50 ± 0.75 , p < 0.05 ) and Panax ginseng extract  lowered hepatic reticular fiber accumulation ( 1.05 ± 0.44 vs 1.60 ± 0.39 , p < 0.01 ) increased by CCl4 . Plasma alanine aminotransferase and aspartate aminotransferase activities were increased by CCl4 ( p < 0.01 ) , and aspartate aminotransferase activity was decreased by Panax ginseng extract at week 9 ( p < 0.05 ) . Exposure to CCl4 for 7 weeks , the levels of plasma and hepatic triglycerides ( p < 0.01 ) , hepatic cholesterol ( p < 0.01 ) , interleukin-1β ( p < 0.01 ) , prostagl and in E2 ( p < 0.05 ) , soluble intercellular adhesion molecule-1 ( p < 0.05 ) , hydroxyproline ( p < 0.05 ) , matrix metalloproteinase-2 ( p < 0.05 ) and tissue inhibitor of metalloproteinase-1 ( TIMP-1 ) ( p < 0.01 ) were elevated , however , hepatic interleukin-10 level was lowered ( p < 0.05 ) . Both Panax ginseng extract and ginsenoside Rb1  decreased plasma and hepatic triglyceride , hepatic prostagl and in E2 , hydroxyproline and TIMP-1 levels  , and Panax ginseng extract further inhibited interleukin-1β concentrations ( p < 0.05 ) . Conclusions Panax ginseng extract and ginsenoside Rb1 attenuate plasma aminotransferase activities and liver inflammation to inhibit CCl4-induced liver fibrosis through down-regulation of hepatic prostagl and in E2 and TIMP-1 AIM Hepatic fibrogenesis has close relation with hepatic stellate cells ( HSC ) and tissue inhibitors of metalloproteinase ( TIMP ) . Oxymatrine ( OM ) is a kind of Chinese herb that is found to have some effects on liver fibrosis . We aim ed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism . METHODS Thirty-two rats were r and omly divided into four groups ; 16 were used to develop hepatic fibrosis by carbon tetrachloride ( CCl4 ) and treated with or without OM , and 16 were used as controls . The expression of tissue inhibitor of metalloproteinase-1 ( TIMP-1 ) and alpha-smooth muscle actin ( alpha-SMA ) in the livers of rats was detected by immunohistochemical assay . Liver pathology was determined by H and E staining and reticulum staining . RESULTS In CCl4-injured rats , the normal structure of lobules was destroyed , and pseudolobules were formed . Hyperplasia of fibers was observed surrounding the lobules . While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment . The pseudolobules were surrounded by strong , multi-layer reticular fibers , which netted into pseudolobules in CCl4-injured rats , however , there was a significant decrease in reticular fibers in OM-treated rats . The expression of TIMP-1 in hepatic cells was weak in control groups , but strong in CCl4-injured groups , however , the expression of TIMP-1 was significantly inhibited by OM ( F = 52.93 , P<0.05 ) . There was no significant change in the expression of alpha-SMA between CCl4-injured rats with or without OM treatment ( F = 8.99 , P>0.05 ) . CONCLUSION OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues , probably by reducing the expression level of TIMP-1 Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo . This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients . In study A , 36 adults with newly diagnosed type 2 diabetes mellitus were r and omly assigned to treatment with berberine or metformin ( 0.5 g 3 times a day ) in a 3-month trial . The hypoglycemic effect of berberine was similar to that of metformin . Significant decreases in hemoglobin A1c ( from 9.5%+/-0.5 % to 7.5%+/-0.4 % , P<.01 ) , fasting blood glucose ( from 10.6+/-0.9 mmol/L to 6.9+/-0.5 mmol/L , P<.01 ) , postpr and ial blood glucose ( from 19.8+/-1.7 to 11.1+/-0.9 mmol/L , P<.01 ) , and plasma triglycerides ( from 1.13+/-0.13 to 0.89+/-0.03 mmol/L , P<.05 ) were observed in the berberine group . In study B , 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial . Berberine acted by lowering fasting blood glucose and postpr and ial blood glucose from 1 week to the end of the trial . Hemoglobin A1c decreased from 8.1%+/-0.2 % to 7.3%+/-0.3 % ( P<.001 ) . Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1 % and 44.7 % ( P<.001 ) , respectively . Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well . During the trial , 20 ( 34.5 % ) patients experienced transient gastrointestinal adverse effects . Functional liver or kidney damages were not observed for all patients . In conclusion , this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism Curcumin , a polyphenolic antioxidant derived from a dietary spice , exhibits anticancer activity in rodents and in humans . Its efficacy appears to be related to induction of glutathione S-transferase enzymes , inhibition of prostagl and in E2 ( PGE2 ) production , or suppression of oxidative DNA adduct ( M1 G ) formation . We design ed a dose-escalation study to explore the pharmacology of curcumin in humans . Fifteen patients with advanced colorectal cancer refractory to st and ard chemotherapies consumed capsules compatible with curcumin doses between 0.45 and 3.6 g daily for up to 4 months . Levels of curcumin and its metabolites in plasma , urine , and feces were analyzed by high-pressure liquid chromatography and mass spectrometry . Three biomarkers of the potential activity of curcumin were translated from pre clinical models and measured in patient blood leukocytes : glutathione S-transferase activity , levels of M1 G , and PGE2 production induced ex vivo . Dose-limiting toxicity was not observed . Curcumin and its glucuronide and sulfate metabolites were detected in plasma in the 10 nmol/L range and in urine . A daily dose of 3.6 g curcumin engendered 62 % and 57 % decreases in inducible PGE2 production in blood sample s taken 1 hour after dose on days 1 and 29 , respectively , of treatment compared with levels observed immediately predose ( P < 0.05 ) . A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the prevention or treatment of cancers outside the gastrointestinal tract . PGE2 production in blood and target tissue may indicate biological activity . Levels of curcumin and its metabolites in the urine can be used to assess general compliance Resveratrol , a naturally occurring polyphenol , has cancer chemopreventive properties in pre clinical models . It has been shown to downregulate the levels of insulin-like growth factor-1 ( IGF-I ) in rodents . The purpose of the study was to assess its safety , pharmacokinetics , and effects on circulating levels of IGF-I and IGF-binding protein-3 ( IGFBP-3 ) after repeated dosing . Forty healthy volunteers ingested resveratrol  at 0.5 , 1.0 , 2.5 , or 5.0 g daily for 29 days . Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28 . IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29 . Resveratrol was safe , but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms .  Resveratrol-3-O-sulfate , resveratrol-4'-O-glucuronide , and resveratrol-3-O-glucuronide were major plasma metabolites . Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol , in the case of areas under the concentration versus time curve , by up to 20.3-fold . Compared with predosing values , the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 ( P<0.04 for both ) , respectively , in all volunteers . The decrease was most marked at the 2.5 g dose level . The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma . The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity Oxymatrine ( OM ) is an alkaloid extracted from the Chinese herb Sophora flavescens Ait . with a variety of pharmacological activities . The aim of this study was to investigate the preventive effects of OM on  bleomycin (BLM)-induced pulmonary fibrosis ( PF ) and to further 
    Output:
    
Gedunin , carnosol , celastrol , black rice anthocyanins , Duchesnea indica , cordycepin and Celastrus orbiculatus extract downregulate vimectin , fibronectin and N-cadherin .
Sulforaphane , luteolin , celastrol , curcumin , a rct igenin inhibit β-catenin signaling pathways .
Salvianolic acid-A and plumbagin block oxidative stress , while honokiol , gallic acid , piperlongumine , brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL , TWIST and ZEB  .
Overall , this opens up new therapeutic alternatives in cancer , inflammatory and fibrosing diseases through the control of EMT process