Objective To explore the mechanism of Sedum sarmentosum extract in improving liver fibrosis based on adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1)/liver X receptors (LXRs) signaling pathway. Methods A rat model of liver fibrosis was established using ip dimethylnitrosamine (DMN), and after intervention with S. sarmentosum extract or Fuzheng Huayu Capsules (扶正化瘀胶囊) for five weeks, serum and liver tissue were collected. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were determined. Hematoxylin-eosin (HE) and Masson staining were used to detect pathological changes in liver tissue. Immunohistochemistry, Western blotting and qRT-PCR were used to detect fibrosis, apoptosis, inflammation, AMPK/SIRT1/LXRs signaling pathway related proteins and gene expressions in liver tissue. Transforming growth factor-β (TGF-β) was used to stimulate hepatic stellate cells (HSCs) for 2 h, followed by treatment with S. sarmentosum extract or AMPK agonist AICAR or LXRβ agonist GW3965 for 6 h. Immunofluorescence staining and Western blotting were used to detect the expressions of fibrosis and AMPK-SIRT1-LXRs signaling pathway related proteins. After transfecting LX-2 cells with AMPK or LXRβ siRNA, TGF-β stimulation was given for 2 h, followed by treatment with S. sarmentosum extract for 6 h. Western blotting was used to detect the expressions of AMPK/SIRT1/LXRs signaling pathway related proteins. Results The results of in vivo experiments showed that S. sarmentosum extract significantly reduced the activities of ALT and AST in serum of rats induced by DMN (P < 0.001), improved pathological changes and extracellular matrix deposition in liver tissue, inhibited cell apoptosis and inflammatory factor expressions in liver tissue (P < 0.001), and upregulated the expressions of AMPK/SIRT1/LXRs signaling pathway related proteins (P < 0.05, 0.01, 0.001). The in vitro experimental results showed that S. sarmentosum extract significantly inhibited the expressions of extracellular matrix related proteins in activated HSCs (P < 0.001), and upregulated the expressions of AMPK-SIRT1-LXRs signaling pathway related proteins (P < 0.001), with similar effects as AMPK agonists or LXRβ agonists. In addition, the absence of AMPK or LXRβ significantly weakened the inhibition of α-smooth muscle actin (α-SMA) in activated LX-2 cells and the activation of AMPK/SIRT1/LXRs signaling pathway by S. sarmentosum extract (P < 0.001). Conclusion S. sarmentosum extract effectively improves the progression of liver fibrosis by mediating AMPK/SIRT1/LXRs signaling pathway, to regulate extracellular matrix homeostasis and inflammatory responses.

Sedum sarmentosum Bunge  /  liver fibrosis  /  hepatic stellate cells  /  liver X receptors  /  AMPK  /  SIRT1  /  sarmentosin