Resistance to artemisinins has led to possible anti malarial combination therapy. This study was undertaken to investigate the effects of co-administration of artesunate and Azadirachta indica leaves extract on antioxidants and certain liver parameters in rats. 24 male rats weighing averagely 190g were randomly selected into four groups, administered therapeutic doses of artesunate and extract namely : Group A (Control), Group B (Extract only)), Group C (Artesunate only) and Group D (Artesunate with extract). Total protein, Cholesterol concentrations, Alanine amino transferase (ALT), Alkaline phosphatase (ALP) and Gamma glutamyl transferase (GGT) activities were determined using international standardized methods. Malondialdehyde, (MDA), reduced glutathione (GSH), phenols, flavonoids, hydroxyl (OH•) and 1-1-diphenyl-2-picryl hydrazyl (DPPH) radicals scavenging effects were determined spectrophotometrically. Results obtained showed significant increases (P≤0.05) in plasma total protein concentrations in all treatment groups compare with controls while a modulatory effect was observed with plasma total cholesterol concentrations as the combined treatment (Group D) reduced this to controls. Artesunate alone elicit significant increases (P≤0.05) in plasma ALT,ALP and GGT activities while the combined treatment group D showed a modulatory effect as these activities were significantly decreased (P≤0.05) nearly to control level. Interestingly rats challenged with artesunate shows significant decreases (P≤0.05) in GSH level compared with group A,B and D while MDA level were significantly decrease (P≤0.05) by group B, C and D compared with controls . Extract shows considerable amount of phenol and flavonoids and also scavenged (OH•) and DPPH radicals by 72.81% and78.60% at 350µg/ml concentrations in-vitro. Results are suggestive of hepatoprotective and modulatory effects of extract on artesunate which may affects its mechanism of action or synergistically enhance its anti malarial activity, an indication that the plant contain bioactive agents which may be characterized for development of drugs in combating Plasmodium falciparum resistance.
