2. Academic Validation
  3. Lycorine relieves the CCl4-induced liver fibrosis mainly via the JAK2/STAT3 and PI3K/AKT signaling pathways

Lycorine relieves the CCl4-induced liver fibrosis mainly via the JAK2/STAT3 and PI3K/AKT signaling pathways

  • Toxicol Appl Pharmacol. 2024 Aug:489:117017. doi: 10.1016/j.taap.2024.117017.
Yue Tang 1,  Zaisheng Zhu 2,  Mengying Li 3,  Lijiao Gao 3,  Xinyi Wu 3,  Jingyi Chen 3,  Yali Zhang 4,  Haiyang Zhao 5,  Zhongxiang Xiao 6
Affiliations

Affiliations

  • 1 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 2 Department of Medicine Care Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: zhuzaisheng@wmu.edu.cn.
  • 3 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 4 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: ya-li000@163.com.
  • 5 Institute of Life Sciences, Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, Zhejiang 325035, China. Electronic address: haiyangwzu@163.com.
  • 6 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China. Electronic address: xiangzi198155@163.com.
PMID: 38925513 DOI: 10.1016/j.taap.2024.117017
Abstract

Liver fibrosis, a progressive process of fibrous scarring, results from the accumulation of extracellular matrix proteins (ECM). If left untreated, it often progresses to diseases such as cirrhosis and hepatocellular carcinoma. Lycorine, a natural alkaloid derived from medicinal Plants, has shown diverse bioactivities by targeting JAK2/STAT3 signaling, but its pharmacological effects and potential molecular mechanisms in liver fibrosis remains largely unexplored. The purpose of this study is to elucidate the pharmacological activity and molecular mechanism of lycorine in anti-hepatic fibrosis. Findings indicate that lycorine significantly inhibited hepatic stellate cells (HSCs) activation by reducing the expression of α-SMA and collagen-1. In vivo, lycorine treatment alleviated carbon tetrachloride (CCl4) -induced mice liver fibrosis, improving liver function, decreasing ECM deposition, and inhibiting fibrosis-related markers' expression. Mechanistically, it was found that lycorine exerts protective activity through the JAK2/STAT3 and PI3K/Akt signaling pathways, as evidenced by transcriptome Sequencing technology and small molecule inhibitors. These results underscore lycorine's potential as a therapeutic drug for liver fibrosis.

Keywords

CCl(4); JAK2/STAT3; Liver fibrosis; Lycorine; PI3K/AKT.

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