Abstract: Objective This experiment aimed to explore protective effect of saikosaponin A (SSa) on hepatic steatosis in rats with non-alcoholic fatty liver disease (NAFLD) by affecting peroxide proliferator activated receptor α(PPARα) signaling pathway. Methods 46 rats were randomly divided into control (n=10), NAFLD model (n=12), SSa-intervened (n=12) and SSa plus GW6471-intervened group (n=12), and NAFLD model was established by high fat diet feeding. After the model completed, the normal saline, or SSa or SSa and GW6471 were given by gavage and intraperitoneal injection, respectively. The hepatic adenosine 5′-monophosphate-activated protein kinase (AMPK), p-AMPK and PPARα expression was detected by Western blotting. The fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were detected and culculated. Results The FBG, FINS and HOMA-IR in model group were (10.2±1.2)mmol/L, (24.2±2.3)mU/L and (11.0±2.1), significantly higher than [(4.7±0.5)mmol/L, (15.3±2.1)mU/L and (3.2±0.4), respectively, P<0.05] in the control, while they decreased greatly in SSa-intervened group as compared to those in the model (P<0.05), e.g. (6.3±0.7)mmol/L, (18.6±2.5)mU/L and (5.2±0.6), respectively, and they increased in SSa and GW6471 combination group as compared to in the SSa-intervened group [(8.1±1.0)mmol/L, (21.7±2.8)mU/L and (7.8±0.9), respectively, P<0.05]; the hepatic index, hepatic TC, TG and free fatty acid levels in the model were (3.3±0.3)%, (0.8±0.1)mmol/g, (1.1±0.1)mmol/g and (543.6±62.7)mmol/g, significantly higher than [(2.2±0.2)%,(0.3±0.1)mmol/g,(0.5±0.1)mmol/g and (406.5±58.9)mmol/g, P<0.05] in the control, they decreased greatly in SSa-intervened group compared to in the model, and they increased greatly in SSa and GW6471 combination intervention group compared to in SSa-intervened group (P＜0.05); the hepatic steatosis improved obviously in SSa- and SSa plus GW6471-intervened groups compared to that in the model; the hepatic PPARα expression and the p-AMPK/AMPK expression ratio in the model decreased greatly compared to in the control (P＜0.05), while they both elevated in SSa-intervened group (P＜0.05), and they decreased obviously in SSa and GW6471-intervened group (P＜0.05). Conclusion SSa could improve hepatic steatosis in rats, which might be related to the activation of PPARα signaling pathway and inhibit insulin resistance.

Key words: Non-alcoholic fatty liver disease, Saikosaponin A, Insulin resistance, Adenosine 5′-monophosphate-activated protein kinase, Peroxide proliferator activated receptor α, Rats