title: A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain.
abstract: BACKGROUND
  The aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents.
  
  
  METHODS
  Meconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities.
  
  
  RESULTS
  Phytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine-antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC50 values of 0.78 μg/mL and 1.29 μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells.
  
  
  CONCLUSIONS
  This study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.
authors.forename: Phurpa
authors.initials: P
authors.lastname: Wangchuk
authors.affiliation: Menjong Sorig Pharmaceuticals, Ministry of Health, Thimphu, Bhutan; School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address: phurpaw@yahoo.com.
authors.forename: Wangchuk
authors.initials: W
authors.lastname: Phurpa
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pyne
authors.forename: Wilford
authors.initials: W
authors.lastname: Lie
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Willis
authors.forename: Roonglawan
authors.initials: R
authors.lastname: Rattanajak
authors.forename: Sumalee
authors.initials: S
authors.lastname: Kamchonwongpaisan
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002470:Cell Survival; D002522:Chlorocebus aethiops; D028101:Papaveraceae; D010936:Plant Extracts / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D001600:Berberine Alkaloids; D010936:Plant Extracts; C009090:protoberberine
keywords: Anticancer; Antimalarial; Bhutanese traditional medicine; Meconopsis simplicifolia; Medicinal plant; Simplicifolianine