Rheumatoid arthritis (RA) is a chronic immune-mediated disease in which persistent inflammation and oxidative stress contribute to progressive joint damage. This study evaluated the prophylactic effects of sabinene in complete Freund's adjuvant (CFA)-induced arthritis and explored potential molecular associations using integrated in vivo and computational approaches. Rats were allocated to vehicle control, arthritic control, piroxicam, or sabinene groups (15, 30, or 60 mg/kg; n = 6/group); sabinene was administered orally beginning 30 minutes before CFA injection and continued for 28 days. Paw swelling, hematological and biochemical parameters, inflammatory and oxidative-stress markers, and gene expression were assessed, followed by network pharmacology, enrichment analysis, and molecular docking. Sabinene dose-dependently attenuated CFA-induced paw swelling and body-weight loss and improved hematological, hepatic, renal, and inflammatory parameters. Treatment also enhanced antioxidant defenses and reduced lipid peroxidation, prostaglandin E₂, 5-lipoxygenase, and anti-cyclic citrullinated peptide antibody levels. Sabinene reduced messenger RNA expression of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, gasdermin D, and other pro-inflammatory genes while increasing interleukin-4 and interleukin-10 expression. Network pharmacology identified 133 overlapping sabinene-RA targets, and molecular docking predicted interactions with tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), and interferon gamma (IFN-γ). These findings support a prophylactic protective effect of sabinene against CFA-induced arthritis associated with reduced inflammation, improved antioxidant status, and modulation of inflammasome-related gene expression. Further protein-level, functional, and post-induction studies are required to confirm the proposed mechanisms and therapeutic relevance.
Kanwal Asif, Ambreen Malik Uttra, Arham Shabbir et al.· Biomolecules & biomedicine· 0 citations
INTRODUCTION/OBJECTIVE
Rheumatoid arthritis is a chronic inflammatory disease of the joints. Geraniol, an acyclic monoterpene alcohol, is present in essential oils of various plants and is known to possess anti-inflammatory, immunomodulatory, and antioxidant properties. The study aimed to evaluate the effects of geraniol on the development of arthritis in a Freund's complete adjuvant (FCA)-induced rat model using a pretreatment (pre-induction) design.
METHODS
Thirty-six Sprague-Dawley rats (100-200 g) of either sex were randomly allocated to six experimental groups using a lottery method: normal control group, arthritic disease control group (FCA 0.15 ml, intradermal), geraniol-treated groups (50, 100, and 200 mg/kg, oral gavage), and standard control group (piroxicam-beta-cyclodextrin 10 mg/kg). Development of arthritis, paw thickness, and paw edema were determined periodically. Hematoxylin and eosin (H&E) staining was performed to examine the histopathological alterations in ankle joints. On day 21, blood samples were collected for hematological evaluations; mRNA expression levels and antioxidant activities of biomarkers were determined using qRT-PCR and spectrophotometric analysis, respectively.
RESULTS
Geraniol pretreatment was associated with reduced arthritic scores, paw edema, and joint thickness compared with the disease control group. Pretreatment with geraniol attenuated alterations in hematological parameters, reduced MDA levels, and improved antioxidant activity by increasing GSH, SOD, and CAT levels. Additionally, it downregulated the expression levels of IL-6, IL-1β, TNF-α, and hypoxia-inducible factor-1α (HIF-1α) compared with the disease control group.
DISCUSSION
Administration of geraniol resulted in the reduction of inflammatory parameters, hematological parameters, and prooxidant markers, and downregulated IL-6, IL-1β, TNF-α, and hypoxia- inducible factor-1α (HIF-1α) associated with rheumatoid arthritis, while increasing antioxidant markers.
CONCLUSION
Geraniol pretreatment was associated with reduced severity of arthritis, lower inflammatory cytokine mRNA expression, and improved oxidative stress markers in an FCA-induced rat model. These findings reflect effects on disease development in a pretreatment (pre-induction) experimental model and do not represent therapeutic efficacy in established rheumatoid arthritis. Further studies using post-induction treatment designs are required to evaluate potential therapeutic relevance.