Analysis of anti-obesity and anti-diabetic effects of acacia bark-derived proanthocyanidins in type 2 diabetes model KKAy mice.

The acacia bark extract derived from Acacia mearnsii De Wild is rich in proanthocyanidins, whose constituent units are robinetinidol, fisetinidol, catechin, and gallocatechin. In this study, we examined the effect of proanthocyanidins on obesity and diabetes using KKAy mice, a type 2 diabetes model. KKAy mice were fed either a low-fat diet, a high-fat diet, or a high-fat diet mixed with an acacia bark extract, a proanthocyanidins fraction, and other fraction for 7 weeks. Monitoring the changes in the body weight revealed that acacia bark extract and proanthocyanidins fraction could prevent excessive weight gain resulting from a high-fat diet. In addition, increases in the fasting blood glucose level due to high-fat diet intake were found to be suppressed by acacia bark extract and proanthocyanidins fraction. Furthermore, proanthocyanidins derived from acacia bark were found to increase the expression of adiponectin in white adipose tissue, which enhances the action of insulin. In addition, acacia bark-derived proanthocyanidins suppressed gluconeogenesis and fatty acid synthesis in the liver, as well as suppressing the decrease in energy production under pathological conditions in skeletal muscle. In addition, acacia bark-derived proanthocyanidins showed AMPK activation and DPP-4 inhibitory action. Therefore, it was suggested that acacia bark-derived proanthocyanidins lowered fasting blood glucose levels through the above mechanism. These results suggest that proanthocyanidins derived from acacia bark are the active ingredients of the anti-obesity and anti-diabetic effects of acacia bark extract.

Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam.

5,7-Dimethoxyflavone (5,7-DMF), one of the major components of Kaempferia parviflora, has anti-obesity, anti-inflammatory, and antineoplastic effects. On the other hand, in vitro studies have reported that it directly inhibits the drug metabolizing enzyme family cytochrome P450 (CYP) 3As. In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF. Midazolam, a substrate of CYP3As, was orally administered to mice treated with 5,7-DMF for 10 days, and its pharmacokinetic properties were investigated. In the group administered 5,7-DMF, the area under the curve (AUC) of midazolam increased by 130% and its biological half-life was extended by approximately 100 min compared to the control group. Compared to the control group, 5,7-DMF markedly decreased the expression of CYP3A11 and CYP3A25 in the liver. These results suggest that continued ingestion of 5,7-DMF decreases the expression of CYP3As in the liver, consequently increasing the blood concentrations of drugs metabolized by CYP3As.