Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Xinping Wang¹, Yue Ming², Qiang Li³, Guiling Li³, Chunmiao Xu³, Meiling Tang³

¹Department of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar City, Heilongjiang Province 161000, China; ²School of Pathology, Qiqihar Medical University, Qiqihar City, Heilongjiang Province 161000, China; ³School of Nursing, Qiqihar Medical University, Qiqihar City, Heilongjiang Province 161000, China.

For correspondence:- Meiling Tang Email: mei_lin_t1220@163.com Tel:+864522663517

Accepted: 27 March 2023 Published: 29 April 2023

Citation: Wang X, Ming Y, Li Q, Li G, Xu C, Tang M. Saikosaponin A alleviates rat liver fibrosis by inhibiting Hedgehog signaling pathway-mediated autophagy and NLRP3 inflammasome. Trop J Pharm Res 2023; 22(4):741-747 doi: 10.4314/tjpr.v22i4.5

© 2023 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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: Liver fibrosis, Saikosaponin A, Autophagy, NLRP3 inflammasome, Hedgehog