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Saikosaponin A alleviates rat liver fibrosis by inhibiting Hedgehog signaling pathway-mediated autophagy and NLRP3 inflammasome

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Purpose: To investigate the effect of saikosaponin A (SSa) on liver fibrosis, and the underlying mechanism of action. Methods: Sprague-Dawley (SD) rats were treated with carbon tetrachloride (CCl4) in an… Click to show full abstract

Purpose: To investigate the effect of saikosaponin A (SSa) on liver fibrosis, and the underlying mechanism of action. Methods: Sprague-Dawley (SD) rats were treated with carbon tetrachloride (CCl4) in an in vivo model of liver fibrosis. The effect of SSa on liver fibrosis was determined by spectrophotometry, Sirius staining, and western blotting. The mechanism of SSa in autophagy and NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome were examined by western blotting. Results: Saikosaponin A treatment reduced CCl4-induced serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hydroxyproline (HYP) content, relative protein expression of alpha-smooth muscle actin (α-SMA), as well as Collagen 1 and deposition of collagenous fiber in liver tissues (p < 0.05). Saikosaponin A administration also downregulated the CCl4-induced protein levels of Hedgehog signaling pathway-related proteins that mediate autophagy and the NLRP3 inflammasome in hepatic tissues (p < 0.05). Conclusion: Saikosaponin A mitigates liver fibrosis by suppressing Hedgehog signaling pathway-mediated autophagy and NLRP3 inflammasome in CCl4-induced rats. Thus, SSa is a potential drug for the management of liver fibrosis.

Keywords: hedgehog signaling; liver fibrosis; signaling pathway; autophagy nlrp3; fibrosis; nlrp3 inflammasome

Journal Title: Tropical Journal of Pharmaceutical Research
Year Published: 2023

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