2. Academic Validation
  3. Arbidol attenuates liver fibrosis and activation of hepatic stellate cells by blocking TGF-β1 signaling

Arbidol attenuates liver fibrosis and activation of hepatic stellate cells by blocking TGF-β1 signaling

  • Eur J Pharmacol. 2024 Mar 15:967:176367. doi: 10.1016/j.ejphar.2024.176367.
Younan Ren 1,  Ying Chen 1,  Emily H Tang 2,  Yixin Hu 3,  Bo Niu 1,  Huaduan Liang 1,  Chuchu Xi 1,  Fang Zhao 4,  Zhengyu Cao 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
  • 2 BASIS International School Nanjing, No.18 Lingshan North Road, Qixia District, Nanjing, Jiangsu, 210023, China.
  • 3 State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; Animal Experiment Center of China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
  • 4 State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: zhaofang0927@cpu.edu.cn.
  • 5 State Key Laboratory of Natural Medicines and Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address: zycao@cpu.edu.cn.
PMID: 38325795 DOI: 10.1016/j.ejphar.2024.176367
Abstract

Chronic liver diseases (CLD) impact over 800 million people globally, causing about 2 million deaths annually. Arbidol (ARB), an indole-derivative used to treat Influenza Virus infection, was extensively used during COVID-19 pandemic in China. In recent years, studies have shown that ARB, compared to other Antiviral drugs, exhibits greater liver-protective efficacy, indicating a potential hepatoprotective effect beyond its Antiviral activity. However, the mechanism remains unclear. In this study, we investigated the impact of ARB on liver injury/fibrosis in bile duct ligated (BDL) mice and its effect on spontaneous and transforming growth factor β1 (TGF-β1)-induced activation of primary cultured hepatic stellate cells (HSCs). Oral administration of ARB significantly ameliorated BDL-induced liver injury/fibrosis as reflected by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced collagen deposition, and diminished mRNA expression of fibrosis markers. ARB notably inhibited spontaneous and TGF-β1-induced activation of primary cultured HSCs. Moreover, ARB also drastically attenuated mRNA expression levels of platelet-derived growth factor receptor (PDGFR), transforming growth factor-beta receptor (Tgfbr) 1, Tgfbr2, matrix metalloproteinase (MMP)-2, and MMP-9 in activated HSCs. We further demonstrate that ARB mitigated SMAD2/3 phosphorylation in both TGF-β1 treated HSCs and BDL mice. These data together demonstrate that the therapeutic efficacy of ARB on liver fibrosis is independent of its Antiviral activity and likely is achieved by blocking TGF-β1 signaling-mediated HSC activation.

Keywords

Arbidol; COVID-19; Hepatic stellate cells; Liver fibrosis; TGF-Smad2/3 signaling.

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