Antidiabetic-like Effects of Naringenin-7-O-glucoside from Edible Chrysanthemum "Kotobuki" and Naringenin by Activation of the PI3K/Akt Pathway and PPARγ.

Obesity is directly associated with type 2 diabetes, hypertension, cardiovascular injury, and cancer. To date, Yamamoto identified that hot water extracts of edible chrysanthemum (EC) induced cell size reduction, up-regulation of adiponectin expression, and glucose absorption inhibition in 3T3-L1 cells during adipogenesis. Furthermore, EC showed anti-diabetic effects such as improvement in insulin resistance and the down-regulation of the blood glucose level and liver lipid content in type 2 diabetes model mice. In the present study, we attempted to identify the antidiabetic components in EC. The methanol fraction from EC that showed relatively strong biological activity was purified by chromatography to obtain acacetin-7-O-glucoside, apigenin-7-O-glucoside, kaempferol-7-O-glucoside, and naringenin-7-O-glucoside. Among the isolated compounds and their aglycones, naringenin (NA) and naringenin-7-O-glucoside (NAG) up-regulated the intracellular lipid accumulation and secretion of adiponectin and down-regulated the diameter of 3T3-L1 cells during adipogenesis. Because the PPARγ antagonist BADGE and PI3K/Akt inhibitors wortmannin and LY29004 inhibited the intracellular lipid accumulation by NA and NAG associated with adipogenesis, it was considered that NA and NAG showed the above-mentioned activities via the activation of PPARγ as well as phosphorylation of the PI3K/Akt pathway.