Diabetes mellitus is one of the most common chronic diseases and a major contributor to the development of cardiovascular diseases. It is due to a deficiency or a failure of normal action of insulin, which is responsible of the use of the sugar from the diet. The number of cases of non-insulin dependent diabetes mellitus has increased dramatically due to the changes in lifestyle, increasing prevalence of obesity, and ageing of populations. 1) In the year 2000, the number of diabetic patients was 151 million and is estimated to rise to 300 million by 2025. 2,3)The uses of natural drugs, such as plants and herbal remedies to treat diseases is very common in Asia and developing countries, where the population is linked with the use of traditional medicines, due to their efficiency or due the costs of the synthetic drugs and/or pharmaceuticals. One of the aims of phytochemists is to find the application of ethnomedicine in drug discovery. Moreover, WHO study groups emphasize strongly the optimal, rational uses of traditional and natural indigenous medicines (http://www.who.int/mediacentre/factsheets/fs134/en/). The leprosy gourd (bitter gourd, ayurveda name: karela), Momordica charantia L., a well known plant for its antidiabetic properties in Asia and some African countries, is among the candidates. Bitter and non-bitter cucurbitane triterpene aglycones and/or glycosides have been isolated from the plant. [4][5][6][7][8][9][10][11] The bitter principles so far reported have been characterized as momordicosides K and L, and momordicines I and II. 5,8) Interestingly, the four compounds have C-9 formyl, 7-OH or O-b-D-glucopyranosyl groups and are unsaturated at C-5, C-6. These features might be the structural requirement for the bitter taste and undoubtedly, the high content of saponins in the plant can be related to its taste.The constituents responsible for the glucose lowering activity are not yet well known even though over hundred scientific articles have described the phytochemical and pharmacological properties of the plant. 12,13) In the course of our phytochemical screening of medicinal plants aimed at finding the active principles for antidiabetic activities, eleven compounds (1-11) were isolated from the Indian bitter gourd sample. The structural elucidation of compounds 1-3 is reported and the major compounds (4 and 5) have been tested against the antidiabetic strain of male ddY mice. The objective of the present study is to find the relationship between Momordica charantia constituents and the antidiabetic properties of the plant. Results and DiscussionEffect of the Extracts on Diabetes Induced Mice The ether and ethyl acetate fractions of the water suspension of the bitter gourds methanol extract were tested for antidiabetic assay in mice. Oral administration of each fraction at 500 mg/kg (Figs. 3, 4, respectively) resulted marked hypoglycaemic effects comparable to glibenclamide (at 200 mg/kg).Isolation and Characterization of Constituents from the Active Extracts A combination of size exclusion and sil...

In type 2 diabetic mellitus, glucose-dependent insulinotropic polypeptide (GIP) secretion is increased, but its insulinotropic effect is severely reduced, perhaps as a result of reduced GIP receptor expression or reduced β-cell sensitivity to GIP (1, 2). In addition, many studies demonstrated a progressive decline in postprandial glucagon-like peptide-1 (GLP-1) secretion, where individuals with type 2 diabetes demonstrate the greatest impairment in GLP-1 secretion (3,4). This difference has been called the incretin effect. Although GLP-1 has been used as a therapeutic drug, the clinical utility of native GLP-1 is limited by its short half-life (within 2 min) due to its rapid degradation to inactive metabolites by the enzyme dipeptidyl peptidase-4 (DPP-4) (5 -8). Therefore, DPP-4 inhibitor is also useful target for the therapy of type 2 diabetic mellitus. Sitagliptin, vildagliptin, saxagliptin, and alogliptin have been used in the clinic.On the other hand, α-lactoalbumin, β-lactoglobulin, and lactoferrin, which are major protein components of bovine milk whey, have been known to have many pharmacological functions such as anti-hypertensive, anti-inflammatory, analgesic, and insulinotropic properties (9). We also reported anti-inflammatory and analgesic activity of α-lactoalbumin (10). Milk products are powerful acute stimulants of insulin secretion (11,12) and have the ability to enhance the insulin response when supplied in a mixed meal (13). Frid et al. (14) reported that acute administration of whey protein-supplemented meals to individuals with type 2 diabetes was associated with significant increments in postprandial insulin responses and higher levels of GIP but not GLP-1. Recently, Tulipano et al. (15) reported that Ile-Pro-Ala, a DPP-4 inhibitor, was isolated from the hydrolysates of β-lactoglobulin, the major whey protein. After oral administration, milk protein is transferred to the duodenum from the stomach and digested by trypsin secreted from the pancreas. We already tested the effects of alpha-lactoalbumin and trypsin-treated alpha-lactoalbumin on DPP-4 activity and found that these proteins did not show any inhibitory effect on DPP-4. However, trypsin-treated β-lactoglobulin showed inhibitory effect on it. Then, we tested the hypoglycemic efficacy of trypsin-treated β-lactoglobulin in the oral glucose tolerance test using mice. Next we isolated the hypoglycemic peptide having DPP-4 inhibiting activity and identified the active amino acid sequence. Research and Development, Meiji Corporation, Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan Received May 12, 2011; Accepted June 29, 2011 Abstract. Trypsin-treated β-lactoglobulin significantly decreased the glucose level after an oral glucose tolerance test using mice. We performed the present study to identify the active peptide inhibiting dipeptidyl peptidase-4 from trypsin-treated β-lactoglobulin. Trypsin-treated β-lactoglobulin showed a concentration-dependent inhibition for dipeptidyl peptidase-4, with an IC 50 value of 210 μM, althoug...

Terpenes U 0200Momordica charantia Constituents and Antidiabetic Screening of the Isolated Major Compounds. -Three new cucurbitane triterpenoids (I) and 8 known compounds are isolated from the methanol extract. The antidiabetic effect of the isolated major constituents is screened. The aglycon of (Ic) significantly decreases the blood glucose levels. -(HARINANTENAINA, L.; TANAKA, M.; TAKAOKA, S.; ODA, M.; MOGAMI, O.; UCHIDA, M.; ASAKAWA*, Y.; Chem.

Abstract. This study aimed to evaluate whether milk whey culture with Propinibacterium freudenreichii ET-3 (milk whey culture), which has been reported to have Bifidogenic activity, is effective on the colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. For the induction of colitis, the colon was clamped and 0.1 M TNBS in 35% ethanol was injected into the luminal side of the clamped portion under pentobarbital anesthesia. From the next day of colitis induction, milk whey culture was administered orally at doses of 1 and 3 g / kg, twice a day for 9 days. On the 10th day, rats were sacrificed and ulcer size was measured. Milk whey culture significantly accelerated the healing of the colitis in a dose-dependent manner, but culture medium did not. To clarify the active substance, the effects of propionic acid and acetic acid contained in milk whey culture was tested. Sodium propionate significantly accelerated the healing of TNBS-induced colitis, but sodium acetate did not. The above results show that milk whey culture may become a useful prebiotic for the therapy of inflammatory bowel disease and that propionic acid may be one of the active substances contained in milk whey culture.

After the screening of microorganism culture, the culture of Propionibacterium freudenreichii ET-3 in the milk whey (milk whey culture) was found to stimulate the growth of our own Bifidobacteria in the colon but not the growth of other microorganisms. One of the active substances was identified as 1,4-dihydroxy-2-naphthoic acid (DHNA).In healthy volunteers, the ingestion containing milk whey culture significantly increased the population of Bifidobacteria to total fecal bacterium. In the TNBS-induced colitis model of rats, milk whey culture significantly accelerated the healing of the colitis in a dose-dependent manner. It has been reported that DHNA inhibited the lymphocyte infiltration through reduction of MAdCAM-1 in DSS colitis model of mice and that the ingestion of milk whey culture was effective in the treatment of ulcerative colitis in human pilot study. These findings suggest that milk whey culture is a useful prebiotic for the therapy of inflammatory bowel disease.