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  3. Trans-anethole enhances mesenchymal stem cell derived exosomes function to inhibit H2O2-induced rheumatoid arthritis-like inflammation in HIG-82 synovial cells

Trans-anethole enhances mesenchymal stem cell derived exosomes function to inhibit H2O2-induced rheumatoid arthritis-like inflammation in HIG-82 synovial cells

  • Mol Biol Rep. 2025 Apr 28;52(1):431. doi: 10.1007/s11033-025-10426-1.
Tai-Lung Huang 1,  Yu-Chun Chang 2 3,  Wei-Wen Kuo 2 4,  Shih-Wen Kao 5 6,  Chia-Hua Kuo 7,  Dennis Jine-Yuan Hsieh 8 9,  Kuan-Ho Lin 10 11,  Tsung-Jung Ho 12 13 14,  Chih-Yang Huang 15 16 17 18
Affiliations

Affiliations

  • 1 Department of Orthopedics, Chung-Kang Branch, Cheng Ching General Hospital, Taichung, Taiwan.
  • 2 Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
  • 3 Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
  • 4 Program for Biotechnology Industry, China Medical University, Taichung, Taiwan.
  • 5 Graduate Institute of Aging Medicine, China Medical University, Taichung, Taiwan.
  • 6 Department of Orthopedic Surgery, Chung-Shan Medical University Hospital, Taichung, Taiwan.
  • 7 Department of Sports Sciences, University of Taipei, Taipei, Taiwan.
  • 8 School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
  • 9 Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.
  • 10 Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan.
  • 11 College of Medicine, China Medical University, Taichung, Taiwan.
  • 12 School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan. jeron888@gmail.com.
  • 13 Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan. jeron888@gmail.com.
  • 14 Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. jeron888@gmail.com.
  • 15 Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan. cyhuang@mail.cmu.edu.tw.
  • 16 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.
  • 17 Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.
  • 18 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.
PMID: 40293555 DOI: 10.1007/s11033-025-10426-1
Abstract

Background: Rheumatoid arthritis (RA) is an auto-immune inflammatory disorder for which an effective cure is yet to be found. Trans-anethole (1-methoxy-4-(1E)-1-propen-1-yl-benzene), a key bioactive compound derived from the perennial plant Foeniculum vulgare, exerts multiple medicinal benefits. In this study, we investigated the therapeutic potential of exosomes derived from anethole-preconditioned human Wharton Jelly-derived mesenchymal stem cells (hWJMSCs) against RA-like inflammation in H2O2-treated synoviocyte HIG-82 cells.

Methods: The fennel samples were prepared and trans-anethole was purified using LC-ESI-MS/MS analysis. The MTT cell viability assays, hWJMSC derived exosomes, and expression analysis of cellular markers related to proliferation, stemness, Apoptosis, and extracellular matrix (ECM)-degrading proteases were performed using Western blotting in HIG-82 cells.

Results: The results showed that anethole treatment significantly increased cell viability and expression of the MSC marker CD90 in a dose-dependent manner in HIG-82 cells. Cell stemness markers, including proliferation markers cyclin-D, proliferating cell nuclear antigen (PCNA), and minichromosome maintenance complex component 2 (MCM2) were enhanced, whereas p53 and p21 were decreased by anethole. Exosomes derived from anethole-preconditioned hWJMSCs significantly improved the cell viability of H2O2-treated HIG-82 cells. Anethole- preconditioned exosomes decreased ECM-degrading proteases MMP-13, ADAMTS-2, -8, and -17, and AQP-3 expression more significantly than exosomes without preconditioned hWJMSC. Bcl-2 was increased, whereas Bax, Cyto c, and c-caspase 3 were decreased by preconditioned exosomes more prominently than exosomes from without preconditioned hWJMSCs in H2O2-treated HIG-82 cells.

Conclusion: Together, the study showed that exosomes derived from anethole-preconditioned hWJMSC have a greater potential to inhibit RA-like inflammation and Apoptosis in H2O2-treated HIG-82 cells.

Keywords

Exosomes; HWJMC; Inflammation; Rheumatoid arthritis; Synoviocytes; Trans-anethole.

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