Ameliorative effects of Asiasarum root and rhizome extract on high fat diet‑induced obesity in mice through regulation of the SIRT1/PGC1α/AMPK pathways in muscle and liver tissues.

Abstract

Asiasarum root and rhizome (Asarum) is commonly used as a diaphoretic. Due to its warm and pungent characteristics in traditional Chinese and Korean medicine, it is considered as having the potential to prevent disease. The present study investigated the effects of Asarum extract on the symptoms of obesity in mice, and the regulation of energy metabolism in the liver and skeletal muscle tissues. In addition, to identify the potential molecular targets and signaling pathways involved in the mechanism of action of Asarum extract in obesity, network pharmacological and molecular docking analysis was performed. In vitro studies demonstrated that Asarum extract significantly increased the expression of regulators of energy metabolism [sirtuin 1 (SIRT1), peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α), nuclear respiratory factor 1, AMP‑activated protein kinase (AMPK) and glucose transporter type 4 (GLUT4)] and myogenic regulatory factors (MyoD, myogenin and myosin heavy chain) in C2C12 myotubes. Furthermore, the in vivo studies demonstrated that Asarum extract could reduce increases in body weight, and the levels of blood glucose, insulin, total cholesterol, triglycerides and low‑density lipoprotein cholesterol in the sera of obese mice. Asarum extract also improved pathological changes in the liver and pancreatic tissues of obese mice, and significantly increased the ratio of brown fat mass to body weight. In addition, Asarum extract reversed the expression of energy metabolism regulators and myogenic regulatory factors in the gastrocnemius tissues of obese mice. Asarum extract also activated the expression of SIRT1, PGC1α and AMPK in the liver tissues of obese mice. These findings indicated that Asarum extract may exert anti‑obesity effects, such as body weight loss, decreases in lipid metabolite levels, and inhibition of pancreatic and liver damage. Using network pharmacological analysis, the mechanisms underlying the effects of Asarum extract on the regulation of energy metabolism were explored, particularly in skeletal muscle and liver tissues.