title: Cryptolepis sanguinolenta: an ethnobotanical approach to drug discovery and the isolation of a potentially useful new antihyperglycaemic agent.
abstract: Evidence has been published that a wide array of plant-derived active principles, representing numerous classes of chemical compounds, demonstrate activity consistent with their possible use in the treatment of patients with Type 2 diabetes mellitus (DM). Despite these interesting observations, to date, metformin is the only ethical drug approved for treatment of Type 2 DM derived from a medicinal plant. Why is this so, given the fact that higher plants are such a potential source of new drugs? The answer to this rhetorical question may lie in the reliance of most pharmaceutical companies on random, in vitro, mechanism-based, high throughput screening in the initial phases of plant drug research. In this article we describe an alternative pathway to discovery of drugs for the treatment of Type 2 DM: on based on an ethnomedical approach, involving ethnobotany and traditional medicine. In particular, we present evidence that cryptolepine, an indoloquinolone alkaloid isolated from Cryptolepis sanguinolenta, significantly lowers glucose when given orally to a mouse model of diabetes. The antihyperglycaemic effect of cryptolepine leads to a significant decline in plasma insulin concentration, associated with evidence of an enhancement in insulin-mediated glucose disposal. Finally, cryptolepine increases glucose uptake by 3T3-L1 cells. These data permit us to conclude that an ethnobotanical approach to drug discovery can identify a potentially useful drug for the treatment of Type 2 DM.
authors.affiliation: Shaman Pharmaceuticals, Inc., South San Francisco, CA 94080-4812, USA.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: D M
authors.initials: DM
authors.lastname: Fort
authors.forename: T J
authors.initials: TJ
authors.lastname: Carlson
authors.forename: B K
authors.initials: BK
authors.lastname: Noamesi
authors.forename: D
authors.initials: D
authors.lastname: nii-Amon-Kotei
authors.forename: S R
authors.initials: SR
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Tsai
authors.forename: J
authors.initials: J
authors.lastname: Quan
authors.forename: C
authors.initials: C
authors.lastname: Hobensack
authors.forename: P
authors.initials: P
authors.lastname: Lapresca
authors.forename: N
authors.initials: N
authors.lastname: Waldeck
authors.forename: C D
authors.initials: CD
authors.lastname: Mendez
authors.forename: S D
authors.initials: SD
authors.lastname: Jolad
authors.forename: D E
authors.initials: DE
authors.lastname: Bierer
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000368:Aged; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D004994:Ethics, Pharmacy; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D026121:Indole Alkaloids; D007211:Indoles; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D010946:Plants, Medicinal / Q000737:chemistry*; D011804:Quinolines; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000470:Alkaloids; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D026121:Indole Alkaloids; D007211:Indoles; D007328:Insulin; D011804:Quinolines; D014665:Vasodilator Agents; C024015:cryptolepine; D005947:Glucose