Deciphering farnesol’s anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification

作者：Shaimaa R. Ahmed, Ambreen Malik Uttra, Muhammad Usman Minhas, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia M. Hendawy, Eman K. Rashwan · 发表于：Journal of Pharmacy and Pharmacology · 年份：2024 · DOI：10.1093/jpp/rgae126 · 被引用次数：5 · 研究领域：Rheumatoid Arthritis Research and Therapies、Inflammatory mediators and NSAID effects、Computational Drug Discovery Methods

OBJECTIVE: Farnesol (FAR), a sesquiterpene alcohol, has documented FAR's anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models. METHODS: Two experimental models comprising formaldehyde- and complete Freund's adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways. KEY FINDINGS: FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis. CONCLUSIONS: The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or c...