title: 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 IC₅₀ value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC₅₀= 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Field Unit, Sector-3, Health Centre, BHEL, National Institute of Malaria Research, Hardwar 249403, India. vkdua51@gmail.com
authors.forename: Virendra K
authors.initials: VK
authors.lastname: Dua
authors.forename: Gaurav
authors.initials: G
authors.lastname: Verma
authors.forename: Bikram
authors.initials: B
authors.lastname: Singh
authors.forename: Aswathy
authors.initials: A
authors.lastname: Rajan
authors.forename: Upma
authors.initials: U
authors.lastname: Bagai
authors.forename: Dau Dayal
authors.initials: DD
authors.lastname: Agarwal
authors.forename: N C
authors.initials: NC
authors.lastname: Gupta
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Ayushi
authors.initials: A
authors.lastname: Rastogi
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D035462:Holarrhena / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032446:Myoblasts / Q000187:drug effects / Q000502:physiology; D059208:Parasite Load; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D010962:Plasmodium berghei / Q000187:drug effects*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D010936:Plant Extracts; C007111:conessine