Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica

Abstract

Background: In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya. Methods: In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits. Results: Compound conessine showed in vitro anti-plasmodial activity with its IC<sub>50</sub> value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC<sub>50</sub>= 14 μg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed. Conclusion: The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.

Citation

Dua, V.K.; Gaurav Verma; Bikram Singh; Aswathy Rajan; Upma Bagai; Agarwal, D.D.; Gupta, N.C.; Sandeep Kumar; Ayushi Rastogi. Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica. Malaria Journal (2013) 12: 194. [DOI: 10.1186/1475-2875-12-194]

Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica

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