Anti-Inflammatory Effects of Zingiber officinale Ethanolic Extract on Immune Biomarkers (Anti-CCP, RF, IL-6, TNF-α) and Hematological Parameters in a Collagen-Induced Arthritis Rat Model

Abstract

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by progressive joint destruction driven by autoimmune and cytokine-mediated inflammatory pathways. Zingiber officinale (ginger) contains bioactive phenolic compounds, principally 6-gingerol and 6-shogaol, that inhibit COX-2, LOX, and NF-κB, thereby reducing cytokine production. Although ginger reduces TNF-α and IL-6 in adjuvant arthritis models, this study examines its effects in the CIA model alongside immune biomarkers and hematological inflammatory indices. Objective: To evaluate the multi-domain anti-inflammatory effects of Z. officinale ethanolic extract (ZOE) at 250 mg/kg/day in the CIA Wistar rat model vs. methotrexate (MTX) as a positive comparator. Methods: Sixty adult male Wistar albino rats were randomized into four groups (n=15 each): G1 control; G2 CIA+vehicle; G3 CIA+ZOE (250 mg/kg/day, Days 28–56); G4 CIA+MTX (0.3 mg/kg/week i.p.). All five biomarker domains were assessed at Day 56 sacrifice: immune (Anti-CCP, RF, hs-CRP, IL-6, and TNF-α); lipid profile with AIP; HOMA-IR; oxidative stress (MDA, SOD, GSH, and NO); and CBC-derived inflammatory indices (NLR, PLR, SII, and MPV). Results: CIA was confirmed in 100% of treated animals. Anti-CCP declined 54.7% (84.8→38.4 U/mL); IL-6 −59.0%; TNF-α −57.9%; hs-CRP fell below the 3.0 mg/L cardiovascular risk threshold. AIP declined from 0.318 to 0.164 (below the 0.21 high-risk threshold). SII declined by 56.1%. Key correlation: AIP vs. hs-CRP r=+0.794 (p<0.001). Conclusion: Zingiber officinale ethanolic extract exerts significant, mechanistically integrated anti-inflammatory effects in CIA, encompassing cytokine suppression, antioxidant restoration, lipid normalization, and hematological inflammatory index reduction. Post-hoc analysis (Tukey's HSD) showed MTX produced significantly greater improvements than ZOE for most parameters, though ZOE's effects on total cholesterol and HDL-C were statistically comparable to MTX (p>0.05); combined with a superior safety profile, these findings support ginger's role as a complementary therapeutic agent in RA management.