α-Glucosidase Inhibitors from Cold-Pressed Black Sesame (Sesamum indicum) Meal: Characterization of New Furofuran Lignans, Kinetic Study, and In Vitro Gastrointestinal Digestion.

Black sesame (Sesamum indicum) meal is an agricultural waste obtained after oil extraction. It is used as a key protein source in animal feed. Previous investigations have indicated that its health benefits, such as antidiabetic activity, are mainly due to its high lignan content. In the present study, we applied α-glucosidase inhibitory guided isolation to identify the active components responsible for the above claim. Twenty-nine compounds, mostly lignans, were isolated and identified, of which five (2-3, 12-13, and 28) were newly isolated. Of the isolated compounds, 20 and 21 were the most potent inhibitors, retarding enzyme function in noncompetitive and uncompetitive manners. Structure-activity relationship analysis suggested that the number of phenolic hydroxyl groups in the structures was significantly related to the inhibitory effect against α-glucosidase. A gastrointestinal digestion study of the major lignan sesaminol triglucoside (STG, 9) suggested that the transformation of dioxymethylene and glucoside moieties gradually began in the late process, thus enhancing the α-glucosidase inhibitory effect.

Four new alkylamides from the fruits of Piper retrofractum and antityrosinase evaluation.

Four new alkylamides named retroframides A-D (1-4) together with twenty-two known compounds were isolated from the fruits of Piper rectrofractum. The structures of new compounds were elucidated on the basis of spectroscopic data including 2D NMR and chemical derivatization followed by GC-MS analysis. Of isolated compounds, piperine (25) and pellitorine (26) revealed moderate inhibition against tyrosinase with percentage inhibition of 36.1 and 40.7.

Black Currant Anthocyanins Attenuate Weight Gain and Improve Glucose Metabolism in Diet-Induced Obese Mice with Intact, but Not Disrupted, Gut Microbiome.

Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 µg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.

Orthosiphol A from the aerial parts of Orthosiphon aristatus is putatively responsible for hypoglycemic effect via alpha-glucosidase inhibition.

An infusion of Orthosiphon aristatus has long been used for diabetes therapy; however, the active principles remained unknown. Herein, we report the identification of the putative agents responsible for this antidiabetic activity using an a-glucosidase-guided isolation. Four flavonoids named sinensetin (1), salvigenin (2), tetramethylscutellarein (3) and 3,7,4'-tri-O-methylkaempferol (4), together with a diterpenoid named orthosiphol A (5), were characterized, based on analysis of their spectroscopic data. Flavonoids 3 and 4 inhibited yeast a-glucosidase with IC,o values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (5) selectively inhibited intestinal maltase with an IC5o, value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner.

Quercitylcinnamates, a new series of antidiabetic bioconjugates possessing α-glucosidase inhibition and antioxidant.

Antidiabetic agents possessing dual functions, α-glucosidase inhibition and antioxidant, have been accepted to be more useful than currently used antidiabetic drugs because they not only suppress hyperglycemia but also prevent risk of complications. Herein, we design antidiabetic bioconjugates comprising of (+)-proto-quercitol as a glucomimic and cinnamic analogs as antioxidant moieties. Fifteen quercitylcinnamates were synthesized by direct coupling through ester bond in the presence of DCC and DMAP. Particular quercityl esters 6a, 7a and 8a selectively inhibited rat intestinal maltase and sucrose 4-6 times more potently than their parents 6, 7 and 8. Of synthesized bioconjugates, 6a was the most potent inhibitor against maltase and sucrose with IC50 values of 5.31 and 43.65 µM, respectively. Of interest, its inhibitory potency toward maltase was 6 times greater than its parent, caffeic acid (6), while its radical scavenging (SC50 0.11 mM) was comparable to that of commercial antioxidant BHA. Subsequent investigation on mechanism underlying inhibitory effect of 6a indicated that it blocked maltase and sucrose functions by mixed inhibition through competitive and noncompetitive manners.

(+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase.

Defatted sesame seeds have been reported for hypoglycemic effect in mice and T2DM women. An attempted to identify active components responsible for this effect was conducted using α-glucosidase-guided fractionation, resulting in the isolation of various lignans. Of compounds isolated, only (+)-pinoresinol showed inhibitory activity against rat intestinal maltase with an IC(50) value of 34.3 µM. The kinetic study indicated that enzymatic hydrolysis of maltose is inhibited by (+)-pinoresinol through competitive and noncompetitive manners. However, a lower dissociation constant (k(i) 288 M) of EI complex suggested that competitive inhibition is predominant over noncompetitive mode (k'(i) 1342 M).