Alleviative effects of Yukmijihwang-tang on cholesterol related disease in a postmenopausal rat model and lipid accumulation in HepG2 cells

Yukmijihwang-tang (YMJT), known as Liu-wei-di-huang-tang in Chinese and Lokumijio-to in Japanese, has been used as a traditional herbal formula for the treatment of various diseases. In Korean traditional medicine, YMJT is a well-known herbal prescription used to relieve Yin-Deficiency. In this study, we examined the effects of YMJT on Nonalcoholic steatohepatitis (NASH) and on diseases associated with cholesterol in a rat model of postmenopausal hyperlipidemia and the methyl-beta-cyclodextrin (M beta CD)-induced hepatic steatosis model in HepG2 cells. Twenty-five rats were ovariectomized (OVX), and five rats were sham-operated (Sham). Then, the OVX rats were randomly assigned to three groups (n = 5): OVX-Con, OVX with simvastatin, and OVX with YMJT (50, 150, 450 mg/kg) for 8 weeks. NASH and a number of targets associated with cholesterol were examined to confirm the effects of YMJT. Oil Red O staining and intracellular cholesterol analyses were used to quantify cellular cholesterol levels. The levels of phosphorylated AMP-activated protein kinases (AMPK) and the products of genes involved in cholesterol synthesis were measured via Western blotting. In OVX rats, YMJT reduced retroperitoneal and peri-renal fat accumulation, serum lipids, the atherogenic index, cardiac risk factors, intima-media thickness, and NASH. YMJT decreased lipid accumulation, total cholesterol, and low-density/very-low-density lipoprotein levels in HepG2 cells. Moreover, YMJT reversed the effects of M beta CD on cholesterol synthesis regulators. Phosphorylation of AMPK was stimulated by YMJT. These results indicated that YMJT has cholesterol-lowering effects both in vivo and in vitro. Therefore, YMJT may have potential as a therapeutic agent for the treatment of hyperlipidemia in postmenopausal females.