Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice

Background & aims: Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis Gerogi. We evaluated the therapeutic effects of wogonin using db/db mice. Methods: Mice received wogonin or vehicle by oral gavage for 2 weeks. Blood glucose, insulin, and cholesterol levels were measured, and liver morphology was observed with histopathological analysis. The mRNA expression levels of PPAR alpha, PPAR gamma, and adiponectin in the liver and white adipose tissue (WAT) were determined by real-time PCR. Immunoblotting for AMPK and PPAR gamma, and adipocyte differentiation were investigated in vitro using 3T3-L1 cells. A luciferase assay was used to measure PPAR alpha and PPAR gamma binding activity. Results: The wogonin group showed decreased weight gain without a change in food intake and improved glucose tolerance. Serum insulin and cholesterol levels in the wogonin group were significantly decreased compared to those in the control group. The wogonin group also showed less accumulation of lipid droplets and glycogen in the liver. PPAR alpha and PPAR gamma expression levels in the liver and WAT and adiponectin expression level in WAT in the wogonin group were higher than those in the control group. In 3T3-L1 cells, wogonin was shown to stimulate AMPK activation in a dose-dependent manner. The presence of wogonin did not affect adipocyte differentiation or PPAR gamma protein level during adipogenesis. Notably, wogonin enhanced PPAR alpha but not PPAR gamma transactivation. Conclusions: These indicate that wogonin may have beneficial effects on glucose and lipid metabolism related to enhanced PPAR alpha and adiponectin expression via AMPK activation. Importantly, wogonin did not cause deleterious effects, such as weight gain and fatty liver. Wogonin might be a useful therapeutic agent to treat type 2 diabetes. (C) 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.