Zishan Liu¹, Yuqin Ren², Lin Zhu³, Yong Hu¹, Min Qi³, Yunliang Guo^1,, Jinbao Zong^3,

Objective: To investigate the hepatoprotective effect and possible mechanism of picroside II in ApoE-/- mice of atherosclerosis. Methods: ApoE-/- mice fed with high-fat diet for 12 weeks were randomly divided into model group, low-, medium- and high-dose of picroside II groups and positive-drug (praluent) group, C57BL/6J mice fed with ordinary feed were the control group. After modeling, Picroside II (5, 20, 40 mg/kg/d) was injected intraperitoneally in treatment group, and praluent (10 mg/kg/w) was given intraperitoneally in the positive-drug group for 12 weeks. The remaining groups were given equal volume saline. Serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected by biochemical assay. The aortic wall lipid deposition and collagen fibers in liver tissue were respectively observed by oil red O staining and Masson staining, the liver function was observed by measuring the content ofGlutamic-oxal (o)acetic transaminase（GOT）and Glutamic-pyruvic transaminase（GPT）and Western blot was used to detect PI3K/Akt pathway and levels of the inflammatory factor interleukin-6 (IL-6) protein. Results: In the control, mice had better mental state and bright fur, while the mental state of mice fed with high-fat diet was slightly worse and more obese. After the end of the administration cycle, compared with the model group, the body weight of mice in the medium and high dose groups and the praluentr group was significantly decreased (P<0.01), the serum levels of TG, TC and LDL-C were significantly decreased (P<0.05) while the HDL-C levels were significantly increased (P<0.05), the lipid deposition area and the collagen volume fraction in liver tissue were significantly decreased (P<0.05), the expressions of PI3K, Akt and IL-6 were significantly decreased (P<0.05). Conclusion: Picroside II could improve lipid metabolism, improve liver fibrosis, which might related to inhibiting the activation of PI3K/Akt signaling pathway.

Picroside II, atherosclerosis, hepatic fibrosis, inflammation, PI3K/Akt signaling pathway