Trans-anethole enhances mesenchymal stem cell derived exosomes function to inhibit H2O2-induced rheumatoid arthritis-like inflammation in HIG-82 synovial cells PMID: 40293555

ADC Targets in Oncology

2026-04-10

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

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. [email protected].
13. Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan. [email protected].
14. Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. [email protected].
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. [email protected].
16. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. [email protected].
17. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. [email protected].
18. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. [email protected].

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.