Ginsenoside Ro ameliorates high fat diet-induced obesity and insulin resistance in mice via activation of the TGR5 pathway.

PMID: 

J Pharmacol Exp Ther. 2021 Apr 5. Epub 2021 Apr 5. PMID: 33820830

Abstract Title: 

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Abstract: 

Obesity is dramatically increasing worldwide. Ginsenosides extracted from ginseng have been reported against obesity and the associated metabolic disorders. As a subtype of ginsenoside, ginsenoside Ro is a critical constituent of ginseng. However, its specific effects on obesity remains unknown. G protein-coupled bile acid receptor 5 (TGR5, also known as GPBAR1) is a bile acid membrane receptor, widely expressed in human tissues contributing to various metabolic processes to confer the regulations of glucose and lipid homeostasis.TGR5 has displayed potentials as a therapeutic target for the treatment of metabolic disorders. Here, we explore the anti-obesity effect of ginsenoside Ro with TGR5 activation screened by a library of natural products. Our results showed that the ginsenoside Ro (90mg/kg) treatment ameliorated body weight and lipid accumulation in multiple metabolic organs of high fat diet-induced obese (DIO) mice without affecting food intake, and improved oral glucose tolerance tests (OGTT), intraperitoneal insulin tolerance tests (IPITT), and fasting serum glucose. We also found that triglyceride (TG) and total cholesterol (TC) in serum and liver were significantly decreased after ginsenoside Ro treatment. Then we usedknockout mice to explore the role ofin the anti-obesity effect of ginsenoside Ro.Our results further demonstrated that ginsenoside Ro promoted glucagon-like peptide-1 (GLP-1) secretion and energy expenditure in wild type DIO mice. However, the stimulation of ginsenoside Ro on GLP-1 secretion and energy expenditure were restrained in theknockout mice.In conclusion, our findings demonstrated that ginsenoside Ro ameliorates obesity and insulin resistance in DIO mice via activating TGR5.Obesityis dramatically increasing worldwide and it contributes to multiple metabolic diseases. TGR5 is a potential therapeutic target for the treatment of metabolic disorders. Ginsenoside Ro, as aoleanane-type ginsenoside, ameliorates obesity and insulin resistance, promotes GLP-1 secretion, increases energy expenditure via activating TGR5. Ginsenoside Ro could be a potential leading compound for treating obesity and its associated metabolic diseases.

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