Anethole mitigates H2O2‐induced inflammation in HIG‐82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway

Author:

Huang Tai‐Lung12,Chang Yu‐Chun13,Tsai Bruce Chi‐Kang3,Chen Tung‐Sheng4,Kao Shih‐Wen5,Tsai Yung‐Yun6,Lin Shinn‐Zong78,Yao Chun‐Hsu9101112,Lin Kuan‐Ho131415,Kuo Wei‐Wen116ORCID,Huang Chih‐Yang317181920ORCID

Affiliation:

1. Department of Biological Science and Technology, College of Life Sciences China Medical University Taichung Taiwan

2. Department of Orthopedics, Chung‐Kang Branch Cheng Ching General Hospital Taichung Taiwan

3. Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Hualien Taiwan

4. School of Life Science National Taiwan Normal University Taipei Taiwan

5. Department of Orthopaedic Surgery Chung‐Shan Medical University Hospital Taichung Taiwan

6. Department of Physical Therapy Asia University Taichung Taiwan

7. Department of Neurosurgery Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Hualien Taiwan

8. Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan

9. Department of Biomedical Imaging and Radiological Science China Medical University Taichung Taiwan

10. School of Chinese Medicine China Medical University Taichung Taiwan

11. Biomaterials Translational Research Center China Medical University Hospital Taichung Taiwan

12. Department of Bioinformatics and Medical Engineering Asia University Taichung Taiwan

13. Division of Cardiovascular Medicine, Department of Internal Medicine China Medical University Hospital Taichung Taiwan

14. Department of Emergency Medicine China Medical University Hospital Taichung Taiwan

15. College of Medicine China Medical University Taichung Taiwan

16. Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan

17. Department of Medical Research China Medical University Hospital, China Medical University Taichung Taiwan

18. Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan

19. Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

20. Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology Hualien Taiwan

Abstract

AbstractRheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti‐arthritic, anti‐inflammatory, antioxidant, and tumor‐suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2O2‐induced inflammation model with HIG‐82 synovial cells. Our results demonstrated that exposure to H2O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2O2. Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2O2 stimulation led to an increase in the AQP1 expression and a decrease in p‐PKA‐C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2O2‐induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments.

Funder

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

National Science and Technology Council

China Medical University Hospital

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine

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