Effects of Samul-tang on hepatic lipid accumulation and hyperlipidemia in a postmenopausal rat model

Samul-tang has been used as a traditional Chinese remedy for the treatment of various diseases. In this study, we examined the phytoestrogenic effects of Samul-tang on breast carcinoma, lipid accumulation in methyl-β-cyclodextrin (MβCD)-induced HepG2 cells, and lipid-related disease in a rat model of postmenopausal hyperlipidemia. An E-screen assay was used on MCF-7 cells, to identify phytoestrogens, especially those with anti-estrogenic activity. Oil Red O staining and intracellular cholesterol analyses were used to quantify cellular cholesterol levels. A 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) assay was used to measure enzyme activity. The levels of phosphorylated AMP-activated protein kinases (AMPK) and products of genes involved in cholesterol synthesis were measured via Western blotting. Thirty rats were either ovariectomized (OVX) or sham-operated (Sham) and then randomly assigned to four groups (n = 5): Sham, OVX, or OVX with simvastatin, or OVX with Samul-tang (50, 150, 450 mg/kg) for 8 weeks. A number of targets associated with lipid-related diseases were examined to confirm the estrogenic effects of Samul-tang. Samul-tang showed anti-estrogenic activity in MCF-7 cells. Samul-tang decreased lipid accumulation, total cholesterol, and low-density/very-low-density lipoprotein levels in HepG2 cells. Moreover, Samul-tang reversed the effects of MβCD on cholesterol synthesis regulators, and inhibited the activity of HMGCR. Phosphorylation of AMPK was stimulated by Samul-tang. In ovariectomized rats, Samul-tang reduced retroperitoneal and peri-renal fat accumulation, serum lipids, atherogenic index, cardiac risk factors, intima-media thickness, and nonalcoholic steatohepatitis scores. These results indicated that Samul-tang inhibits lipid accumulation without estrogenic activity in the breast. Therefore, Samul-tang may have potential as a therapeutic agent for the treatment of hyperlipidemia in postmenopausal females.