Protective Effects of Geraniol in Rheumatoid Arthritis Through Attenuation of Inflammation and Oxidative Stress

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.

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.

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.

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.

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.