1. Field of the Invention
The present invention relates to a pharmaceutical composition for preventing or treating diabetes or dementia, comprising centipede grass (Eremochloa ophiuroides) extracts or the fractions thereof as an active ingredient.
2. Description of the Related Art
According to the rapid economic development and improvement of life style and westernization, it is good to see the desirable physical development, but at the same time disease pattern has also been changed into the westernized adult diseases caused by excessive intake of high-caloric diet, lack of exercise, and stress accompanied by the advancement of industrial society. The most representative adult diseases are liver disease, hypertension, diabetes, obesity, and hyperlipidemia, etc.
One of those representative adult diseases, diabetes, is a non-communicable chronic disease, which is caused by the lack or malfunction of insulin secreted in β cells of pancreas so that glucose cannot be used as an energy source in vivo and stays in the blood at high concentration to be excreted later in urine. Diabetes is divided according to the cause and the method for treating symptoms largely into two groups; which are insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). In Korea, at least 95% of diabetes patients are NIDDM patients. Diabetes has been a serious social issue not because the disease itself is a serious one but because it accompanies complications such as diabetic neuropathy, retinopathy, cataract, and nephropathy that can be a barrier for the patients to lead an ordinary life and further causes a lethal result.
The most common anti-diabetic agents are mainly divided into two groups; which are oral hypoglycemic agents and insulin injections. In general, the insulin injections are recommended for insulin dependent diabetes patients lack of insulin secretion in vivo; gestational diabetes patients; and non-insulin dependent diabetes patients having difficulty in regulating blood glucose by oral hypoglycemic agents. In the meantime, the oral hypoglycemic agents are recommended for non-insulin dependent patients having difficulty in regulating blood glucose with diet therapy and exercise. The oral hypoglycemic agents are exemplified by sulfonylurea-based drugs and biguanide-based drugs.
The sulfonylurea-based drugs, which are exemplified by glipizide, gliclazide, gliquidone, glibenclamide, and chlorpropamide, play a role in accelerating insulin secretion in pancreas, but they cannot be used for those insulin dependent diabetes patients particularly characterized by non-secretion of insulin and only can be applied to those who are non-insulin dependent patients showing comparatively weak insulin secretion. The said drugs cannot be used for woman of childbearing age because of the risk of giving birth to a deformed child, miscarriage, and stillbirth, etc. Most sulfonylurea-based drugs are metabolized in the liver and then excreted through the kidney, suggesting that the administration to the renal or liver dysfunction patients has to be carefully considered.
The biguanide-based drugs exemplified by metformin have been known to increase insulin secretion in pancreas even though the drug mechanism has not been disclosed, yet. Hypoglycemic effect of the biguanide-based drug is lower than that of the sulfonylurea-based drug but the risk of causing hypoglycemia is also low. However, these drugs could cause side effects in digestive system carrying nausea, vomiting, diarrhea, and rash, etc in the early stage of treatment, and also cause lactic acidosis that might be a lethal side effect threatening a life. So, these drugs are allowed for the experimental use only in US.
Since the recent sulfonylurea-based drugs or biguanide-based drugs have problems or side effects, it is requested to develop a safer hypoglycemic agent with less side effects that can be advantageously used for treating the increasing diabetes patients domestically or internationally.
The recent synthetic anti-diabetic agents also have serious side effects and cause drug resistance as well with reducing the drug effect. Therefore, studies have been actively going on to develop or screen a novel material from natural sources that has anti-diabetic activity, instead of using those chemosynthetic anti-diabetic agents.
In the normal brain, neurofibrillary tangles and amyloid plaques are not observed. However, in the brain of dementia patient, neurofibrillary tangles are formed in neurons and amyloid plaques are formed outside of the neurons.
Not only the formation of neurofibrillary tangles and amyloid plaques, which are major causes and characteristics of dementia, but also genetic factors such as presenilin, beta-APP (beta-amyloid precursor protein), and ApoE (apolipoprotein) and other factors are all involved in the development of dementia. Among these, particularly tau protein and beta-amyloid inducing the formation of amyloid plaques and neurofibrillary tangles are believed to be the most important factors. Beta amyloid plaque, one of the representative characteristics of dementia (Alzheimer's disease), is found in between neurons and is the result of the accumulation of abnormal beta-amyloid. The increase of beta-amyloid and hyperphosphorylated tau protein in brain neurons can reduce the level of acetylcholine that is a neurotransmitter involved in memory and learning. So, dementia patients display poor memory and judgment thereby. Dementia is a neurodegenerative disease developed with aging, particularly caused by the selective apoptosis of neurons.
APP (amyloid precursor protein) is generated by the gene located in chromosome #21, which is a glycoprotein belonging to type I transmembrane family expressed in neuroglial cells and neuroblasts. As a cell surface receptor, APP regulates cell adhesion and neurite growth and is also involved in cell signaling pathway to accelerate the growth of neurons and to protect thereof. The mutation of APP is a cause of familial dementia (familial Alzheimer's disease). The abnormal APP mediated Aβ generation is the most crucial pathological step of dementia. Aβ is a protein having the molecular weight of 4 kD which is generated when APP is digested with the proteases called β and γ secretase. Particularly, the mutation of prosenilin (PS1) and PS2 affecting the degradation of APP by the secretase or the mutation of APP induces the abnormal accumulation of Aβ. Aβ is a water-soluble protein generated in the course of normal cell metabolism and then secreted into extracellular space.
APP is a type 1 membrane protein, which plays an important role in the development, differentiation, and survival of neurons. In normal APP metabolism, the generation of Aβ is blocked and non-amyloidogenic pathway progresses. At this time, the protease called secretase is the first one to act. APP NTF (sAPPα) and APP CTF (C83) are generated by α-secretase, which are cut by γ-secretase again to produce P3 that is a peptide shorter than Aβ and not deposited in senile plaque and APP intracellular domain (AICD) fragment. To generate Aβ which is the major component of senile plaque usually shown in dementia patients, APP is first cut by β-secretase to produce APP NTF (sAPPβ) and APP CTF (C99), leading to the amyloid synthesis pathway. The APP CTF (C99) previously digested with β-secretase is now cut again by γ-secretase, and the fragment produced thereby is deposited in the brain tissue to produce Aβ and AICD known to make senile plaque.
The activated β-secretase and γ-secretase increase the production of Aβ 1-42 and the increased Aβ40 and Aβ42 increase pre-fibrillar aggregates, resulting in the formation of amyloid plaque that is a cause of dementia.
To overcome the problem of the aggregation of amyloid plaque, it is necessary to develop a novel anti-dementia agent by using a natural bioactive material. The natural bioactive material is advantageous because it has less side effects than the chemosynthetic material and has excellent stability and safety resulted from the less longitudinal/chemical changes. Thus, studies have been focused on such natural plant resources that display pharmaceutical effect on dementia.
Centipede grass (Eremochloa ophiuroides) is warm-season turfgrass whose growth is late and creeping. This grass is perennial, which grows in a chunk of turf. Centipede grass belongs to Poaceae, and the scientific name thereof is Eremochloa ophiuroides (Munro) Hack. It is mainly distributed in China, East Asia, Indichina, Northeastern United States, Mesoamerica and Caribbean regions. It endures various kinds of soil but particularly prefers humid acidic soil and sandy soil with low fertility. In relation to its morphological characteristics, the leaf is 15˜30 mm in length and 2˜4 mm in width and is flat with a white mid vein. It does not have hairs except collar part and the tip of leaf is round. The stem has a compressed sheath and the roots are stolons having thin branches. The flower of it has a raceme in 3˜5 inches. This raceme is purple and slightly flat-shaped and has two rows of spikelets. This plant is mainly used as lawn grass or turf. It can also be used as bird-feeds owing to its leafiness and good taste.
Studies have been focused on the use of centipede grass for the prevention and treatment of obesity, for the prevention and treatment of cancer, for the prevention of skin aging, and for skin whitening, etc. However, any statement saying which component of centipede grass has what kind of pharmaceutical effect has not been made yet. In particular, the effect of centipede grass in relation to diabetic disease and dementia has not been reported, yet.
In the course of study on the natural plants displaying an excellent treatment effect on diabetes, the present inventors confirmed that centipede grass extracts, fractions thereof, and active fragments separated from those fractions could efficiently regulate blood glucose, leading to the completion of the present invention by further confirming that the centipede grass, the fractions thereof, and the active fragments separated therefrom could be effectively used as a novel anti-diabetic agent.
The present inventors also studied to develop a natural plant extract for treating dementia. As a result, the present inventors confirmed that the centipede grass extract, the fractions thereof, and the active fragments separated from those fractions could inhibit the activity of amyloid-beta (Aβ) in the animal model. Thus, the present inventors proposed the centipede grass extract, the fractions thereof, and the active fragments separated therefrom could be efficiently used as an active ingredient for a composition for the prevention and treatment of dementia, leading to the completion of this invention.