Phyllodulcin, a natural functional sweetener, improves diabetic metabolic changes by regulating hepatic lipogenesis, inflammation, oxidative stress, fibrosis, and gluconeogenesis in db/db mice

Phyllodulcin, an isocoumarin derivatives and well-known natural sweetener derived from Hydrangea macrophylla var, was evaluated for its roles in diabetes-related metabolic and genetic changes by regulating glucose homeostasis in the liver. C57BL/KsJ-db/db mice received 20 mg/kg body weight (b.w.) stevioside (SVS 20), 10 mg/kg b.w. phyllodulcin (P 10), or 20 mg/kg b.w. phyllodulcin (P 20) for four weeks. Water and food intake were significantly lower in the phyllodulcin supplemented group compared with the diabetic group. Phyllodulcin supplementation suppressed the levels of fasting blood glucose, HbA1c, and plasma and hepatic triglyceride level. Phyllodulcin improved hepatic lipogenesis, while also suppressing inflammation and oxidative stress. Phyllodulcin inhibited hepatic fibrosis and regulated liver glucose homeostasis. Thus, these results indicate the potential of phyllodulcin to serve as a therapeutic agent to improve global hepatic function and metabolic abnormalities of diabetic conditions and the necessity to be better explored.