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

Abstract

The research is expected to assess the effect of Annona Reticulata Methanolic leaves Extract (ARME) on progression of adjuvant induced arthritis in Wistar rats. ARME was obtained through bioactivity guided fraction by 5-Lipooxygenase inhibitory activity. ARME was administrated at 100 and 200mg/kg body weight via oral route for a period of 35 days to the experimental models. On day 8, via a single intra-plantar injection of 0.1mL suspension of heat killed Mycobacterium tuberculosis (100μg/animal) Arthritis was induced, in incomplete Freund’s adjuvant of left foot pads of Wistar rats (female). The paw volume was observed by recording the hematological and biochemical parameters, hind limb paw volume, pathological and radiography changes to evaluate the effect of the extract. On day 35, levels of pro-inflammatory cytokines (TNF-a, IL-1Β) and inflammatory mediators (PGE2, LTB4) was measured in serum samples. On the day of sacrifice, the liver was collected to record the stabilizing ability of lipid peroxide, activities of enzymatic antioxidants catalase, Superoxide Dismutase (SOD) and non-enzymatic antioxidants reduced glutathione (GSH) levels. ARME treated groups; 100 and 200mg/kg and prednisolone 10mg/kg significantly decreased hind paw volume, reduced serum levels of TNF-a, IL-1Β, PGE2 and LTB4, reduced MDA levels and increased levels of catalase, SOD and GSH in the liver. The promising results of serum biochemistry, haematology, histopathology and radiographic changes suggest that the administration of ARME was able to effectively modulate the inflammatory response and conquer the advancement of arthritis in the experimental animal model. Results obtained from the acute oral toxicity limit test establish that ARME (LD50>2000mg/kg) was safe in accordance to the OECD guideline 423. These findings may help to overcome some hurdles in the treatment of rheumatoid arthritis.