Zanthoxylum bungeanum-derived extracellular vesicles alleviate liver fibrosis via TGF-β1/Smad pathway

  • Tao Jiang School of Laboratory Medicine, North Sichuan Medical College, Nanchong 637100, China; Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu 610031, China
  • Ruiling Fan Institute of Materia Medica, School of Pharmacy, North Sichuan Medical College, Nanchong 637100, China
  • Bingqi Zhang Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu 610031, China
  • Juan Xiong Department of Laboratory Medicine, Chengdu Qingbaijiang District People’s Hospital, Chengdu 610300, China
  • Ningjing Pu Department of Laboratory Medicine, The Third People’s Hospital of Chengdu, Chengdu 610031, China
  • Mingcai Zhao Department of Laboratory Medicine, Suining Central Hospital, Suining 629000, China
  • Qianyuan Gong Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu 610031, China
  • Yuanbiao Guo School of Laboratory Medicine, North Sichuan Medical College, Nanchong 637100, China; Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu 610031, China
DOI: https://doi.org/10.62617/mcb1357
Keywords: alcohol; edible and medicinal plant; liver fibrosis; hepatic stellate cells
Article ID: 1357

Abstract

The activation of hepatic stellate cells (aHSCs) play a role for the occurrence and progression of liver fibrosis. However, effective drugs that can prevent or reverse this pathological process remain unavailable. Zanthoxylum bungeanum Maxim. (Rutaceae) is an edible and medicinal plant with diverse bioactivities, including antiparasitic, antimicrobial, and anti-inflammatory effects. This study investigates the therapeutic potential and underlying mechanisms of Zanthoxylum bungeanum-derived extracellular vesicles (ZEVs) in liver fibrosis, using the human HSCs LX-2 cells and alcohol-induced mice model of liver fibrosis. The results show that ZEVs significantly inhibit the proliferation and migration of LX-2 cells, while downregulating the fibrosis-related proteins and genes expression. Furthermore, oral administration of ZEVs significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice with liver fibrosis, reducing liver inflammation, collagen deposition, and lipid droplet accumulation. Additionally, miR-9 and miR-17 in ZEVs were found to significantly reduce the synthesis of fibrosis-related proteins in activated LX-2 cells. Mechanistic studies further revealed that ZEVs suppressed the gene levels of TGF-β1, Smad2 and Smad3 in activated LX-2 cells. In conclusion, ZEVs are a possible treatment option for liver fibrosis, potentially through modulation of the TGF-β1/Smad signaling pathway.

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Published
2025-02-19
How to Cite
Jiang, T., Fan, R., Zhang, B., Xiong, J., Pu, N., Zhao, M., Gong, Q., & Guo, Y. (2025). Zanthoxylum bungeanum-derived extracellular vesicles alleviate liver fibrosis via TGF-β1/Smad pathway. Molecular & Cellular Biomechanics, 22(3), 1357. https://doi.org/10.62617/mcb1357
Issue
Vol. 22 No. 3 (2025)
Section
Article

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