Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet-activating factor-mitogen-activated protein kinase axis.

Abstract

Liver fibrosis is a tissue repair process that occurs following various types of chronic liver injury and can develop into liver cirrhosis, portal hypertension or liver cancer without effective treatment. Shikonin has anti-inflammatory, antiviral and antitumor properties. Furthermore, shikonin has an additional effect of antagonizing tissue and organ fibrosis. The aim of the present study was to evaluate the mechanisms of action underlying shikonin against liver fibrosis. Cell viability was assessed using the Cell Counting Kit-8 and EdU incorporation assays. Protein and mRNA expression levels were measured via western blotting and immunofluorescence assays, respectively. Apoptosis was examined via flow cytometry and autophagy via transmission electron microscopy. Compared with the control group, shikonin did not significantly alter LX-2 cell viability at 0.2 µmol/ml, which was used as the intervention concentration. However, shikonin significantly inhibited fibrosis, as indicated by a decrease in the expression of α-smooth muscle actin and collagen-I in the TGF-β + shikonin group compared with the TGF-β group. The results indicated that shikonin potentially inhibited fibrosis via promoting cell apoptosis and inhibiting autophagy. Additionally, the results of the present study indicated that shikonin downregulated the expression levels of platelet-activating factor (PAF) in TGF-β-treated cells, which subsequently activated the MAPK signaling pathway, leading to enhanced cell apoptosis and reduced autophagy. Collectively, the present study indicated that shikonin promoted cell apoptosis and suppressed autophagy via the PAF-MAPK axis in LX-2 cells, thus blocking the development of fibrosis. The results of the present study may provide a potential therapeutic strategy for liver fibrosis.

• Authors: Min Song, Heng Zhang, Zhitao Chen, Jing Yang, Jie Li, Sue Shao, Jing Liu
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 21 Issue 1 Pg. 28 (Jan 2021) ISSN: 1792-0981 [Print] Greece
• PMID: 33262814 (Publication Type: Journal Article)
• Copyright: Copyright © 2020, Spandidos Publications.