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

Abstract
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 proinflammatory
mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its antiarthritic
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 complementary therapy for arthritis.