Anti-Arthritic Activity of Annona Reticulata Leaves Methanolic Extract on Adjuvant Induced Arthritis in Rats

The current research aimed to evaluate the anti-arthritic effect of Annona reticulata methanolic leaves extract (ARME) on the progression of adjuvant-induced arthritis in Wistar rats. ARME was obtained by bioactivity-guided fractionation based on 5-Lipooxygenase inhibitory activity. The ARME was administered orally at dosages of 100 and 200 mg/kg body weight for 35 days. Arthritis was induced on day 8 by a single intra-plantar injection of 0.1 ml suspension of heat-killed Mycobacterium tuberculosis (100 μg/animal) in incomplete Freund’s adjuvant in the left foot pads of female Wistar rats. The anti-arthritic activity was assessed by measuring hind limb paw volume, biochemical and hematological parameters, and pathological and radiographic changes. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and inflammatory mediators PGE2 and LTB4 were measured in serum samples on day 35. The stabilizing ability of lipid peroxide and activities of enzymatic antioxidants catalase, superoxide dismutase (SOD), and non-enzymatic antioxidants reduced glutathione (GSH) levels were measured in the liver. Treated groups ARME 100 and 200 mg/kg and prednisolone 10 mg/kg showed significant decreases in hind paw volume, serum levels of TNF-α, IL-1β, PGE2, and LTB4, reduced MDA levels, and increased levels of catalase, SOD, and GSH in the liver. Promising results in serum biochemistry, hematology, histopathology, and radiography suggest that ARME effectively modulates inflammatory response and mitigates arthritis progression in this experimental model. The safety of ARME was established with an LD50 > 2000 mg/kg according to OECD guideline 423, indicating potential for improved rheumatoid arthritis treatment.