The protective effect of Sedum sarmentosum Bunge against DMN-induced liver fibrosis via Sirt1-AMPK-LXR signaling pathway

[Speaker] Yan-Ling Wu:1
[Co-author] Xin Han:1, Jian Song:1, Li-Huan Lian:1, Ji-Xing Nan:1
1:College of pharmacy, Yanbian University, Jilin Province, China

Objective: The chronic hepatic fibrosis model and activated hepatic stellate cells by using the valuable dimethylnitrosamine to explore the effects of Sedum sarmentosum Bunge (SS) on hepatic fibrosis.
Methods: In vivo, the rats were divided into normal group, DMN group, DMN and SS groups. Liver fibrosis was induced by intraperitoneal injection of 1% DMN on three consecutive days per week for up to five weeks. At the end, blood and liver tissues were collected. In vitro, HSC-T6 and LX-2 cells were exposed to TGF-b (10ng/ml) 2h before treatment with SS 6h. In addition, TGF-b (10ng/ml) stimulated HSC-T6 and LX-2 cells for 2h, and then treated with SS, AICAR(AMPK agonist) and GW3965(LXR agonist) for 6 hours , then collecting cells to extract total protein and nuclear protein for detection.
Results: The results showed DMN-induced rats liver injury by that the activity of ALT and AST in serum was significantly inhibited. H&E staining and Masson staining showed that SS could significantly improve the liver tissue lesion induced by dimethylnitrosamine in a dose-dependent. The expression of a-SMA, Collagen I, TIMP-1 protein and mRNA in liver tissue was inhibited, and the results were consistent with a-SMA immunohistochemical results. The results of RT-PCR showed that the expression of SREBP1, ACCa and FASN was significantly decreased. The expression of Caspase1 and TNFa in the liver can be inhibited, and SS reduce the expression of FLIPL, inhibition of Bid, resulting in a increasing expression of cleaved-Bid, then Bax expression was inhibited, thereby increasing the level of Bcl-2. The expression levels of SIRT1, p-AMPKa, LXRa and LXRb were significantly increased in the high dose group. In vitro, results showed that SS could significantly reduce the expression of a-SMA and CollagenI in hepatic stellate cells to inhibit the activation of hepatic stellate cells. In addition, SS significantly promote the activation of Sirt1, LXRa, LXRb and AMPK phosphorylation in hepatic stellate cells in a dose-dependent manner.
Conclusion:SS can inhibit the fibrosis and reduce the accumulation of fat, inhibit inflammation and apoptosis, and the activation of Sirt1-AMPK-LXR signaling pathway significantly inhibits dimethylnitrosamine-induced hepatic fibrosis and activation of hepatic stellate cells

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