Anethole mitigates H 2 O 2 -induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway

• Published in: Environmental toxicology 2024-02, Vol.39 (2), p.965-978
• Main Authors: Huang, Tai-Lung, Chang, Yu-Chun, Tsai, Bruce Chi-Kang, Chen, Tung-Sheng, Kao, Shih-Wen, Tsai, Yung-Yun, Lin, Shinn-Zong, Yao, Chun-Hsu, Lin, Kuan-Ho, Kuo, Wei-Wen, Huang, Chih-Yang
• Format: Article
• Language: English
• Subjects: Aquaporin 1; Arthritis, Rheumatoid - metabolism; Cell Proliferation; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases - metabolism; Female; Fibroblasts - metabolism; Humans; Inflammation - pathology; Male; Synoviocytes - metabolism
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.24023

Rheumatoid 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 H O -induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H O induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H O . Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H O 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 H O -induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments.