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

J Pharm Pharmacol. 2025 Jan 6;77(1):127-141. doi: 10.1093/jpp/rgae126.

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 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 complementary therapy for arthritis.

Keywords: CFA; farnesol; formaldehyde; network pharmacology; rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Arthritis, Experimental* / drug therapy
  • Farnesol* / pharmacology
  • Farnesol* / therapeutic use
  • Formaldehyde
  • Freund's Adjuvant
  • Immunomodulating Agents / pharmacology
  • Inflammation Mediators / metabolism
  • Interleukin-17 / metabolism
  • Male
  • Mice
  • Network Pharmacology*
  • Rats
  • Signal Transduction* / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Farnesol
  • Anti-Inflammatory Agents
  • Formaldehyde
  • Freund's Adjuvant
  • Immunomodulating Agents
  • Interleukin-17
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha