The current research has aimed to evaluate the anti-arthritic effect of Annona muricata methanolic leaves extract (AMME) on the progression of adjuvant induced arthritis in Wistar rats. AMME was obtained by bioactivity guided fraction by 5-Lipooxygenase inhibitory activity. The AMME was administrated orally at 100 and 200 mg/kg body weight for 35 days to the experimental animals. 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 of left foot pads of female Wistar rats. The anti-arthritic activity extract was screened by measuring hind limb paw volume, biochemical and haematological parameters, pathological and radiography changes. The levels of pro-inflammatory cytokines TNF-α, IL-1β and inflammatory mediators PGE2, LTB4 was 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 liver. Treated groups AMME 100 and 200 mg/kg and prednisolone 10 mg/kg significantly decreased hind paw volume, diminished serum levels of TNF-α, IL-1β, PGE2 and LTB4, reduced MDA levels and increased levels of catalase, SOD and GSH levels in liver and promising results of serum biochemistr y, haematology, histopathology and radiographic changes suggests the administration of AMME was effective in modulating the inflammatory response and conquer the advancement of arthritis in experimental animal model. The safety of AMME was established (LD50 >2000 mg/kg) by acute oral toxicity limit test according to OECD guideline 423. These findings may help to improve the treatment of rheumatoid arthritis.
