Mechanism of Xiaoyaosan in Improving Abnormal Lipid Metabolism and Steatohepatitis of Ovariectomized Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of Xiaoyaosan (XYS) on hepatic lipid metabolism and steatohepatitis in ovariectomized (OVX) female SD rats and its mechanism. Method:Forty female SD rats were randomly divided into sham surgery group, OVX group, low-dose XYS group (3 g·kg-1), and high-dose XYS group (9 g·kg-1). Bilateral ovaries of rats were excised to replicate the obesity model of ovariectomized rat. After 6 weeks of intragastric administration, the change rate of body mass in each group, the levels of blood lipids and liver function of rats were detected. Hematoxylin-eosin (HE) staining and oil red staining were used to observe the hepatocyte histomorphology and the intrahepatic fatty deposits. The expressions of hepatic proinflammatory cytokines and estrogen receptor beta (ERβ) were determined by quantitative real time polymerase chain reaction (Real-time PCR). Result:Compared with sham surgery group, the change rate of body mass of OVX group was significantly increased (2-6 weeks) with the changes in the course of drug administration and the levels of serum total cholesterol (TC), alanine aminotransferase (ALT) (P<0.05), aspartate amino transferase (AST) (P<0.01), low-density lipoprotein (LDL) (P<0.05) were markedly increased too (P<0.05, P<0.01). By histological method, in OVX group, the structure of hepatic cord became disordered, and there were new lipid droplets in hepatocyte cytoplasm, transcription levels of hepatic interleukin-1β (IL-1β) and interleukin-6 (IL-6) in OVX group were significantly increased (P<0.05). Compared with OVX group, the growth rate of body weight in low-dose and high-dose XYS group showed significant decreases with the increase of the cycle of drug administration (3-6 weeks). XYS significantly reduced levels of serum TC, ALT, AST, and LDL levels of OVX rats (P<0.05) in a dose-dependent manner, while serum triglyceride (TG), alkaline phosphatase (AKP) and high-density lipoprotein (HDL) levels in the four groups showed no statistical significance, XYS can improve hepatocyte structure and steatosis of OVX rats, XYS could reduce the transcription hepatic levels of IL-6 and IL-1β of OVX rats in a dose-dependent manner (P<0.05, P<0.01), but there was no significant difference in the transcription level of tumor necrosis factor-α (TNF-α) among groups, both low and high-dose XYS can increase the transcription hepatic level of ERβ in OVX group (P<0.05, P<0.01). Conclusion:XYS can improve the growth rate of body mass, the hepatic lipid metabolism abnormalities and steatohepatitis of OVX rats. The mechanism may be related to the elevated expression of hepatic ERβ by XYS, so as to inhibit the hepatic pro-inflammatory factors expressions.