Cryptolepis sanguinolenta: an ethnobotanical approach to drug discovery and the isolation of a potentially useful new antihyperglycaemic agent

• Published in: Diabetic medicine Vol. 15; no. 5; pp. 367 - 374
• Main Authors: Luo, J., Fort, D.M., Carlson, T.J., Noamesi, B.K., nii-Amon-Kotei, D., King, S.R., Tsai, J., Quan, J., Hobensack, C., Lapresca, P., Waldeck, N., Mendez, C.D., Jolad, S.D., Bierer, D.E., Reaven, G.M.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.1998; Blackwell
• Subjects: Adipose Tissue - cytology; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Aged; Alkaloids - isolation & purification; Alkaloids - pharmacology; Alkaloids - therapeutic use; Animals; antihyperglycaemic agents; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Cell Line; Cryptolepis sanguinolenta; Diabetes Mellitus, Type 2 - drug therapy; drug discovery; Drug Evaluation, Preclinical; Ethics, Pharmacy; ethnobotany; ethnomedicine; General pharmacology; Glucose - pharmacokinetics; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; Indole Alkaloids; Indoles; Insulin - blood; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Obese; Middle Aged; Miscellaneous; Pharmacology. Drug treatments; Plants, Medicinal - chemistry; Quinolines; Type 2 diabetes mellitus; Vasodilator Agents - isolation & purification; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use; United States; North America; America; Endocrinopathy; Human; Ethnobotany; Treatment efficiency; Rodentia; Asclepiadaceae; Non insulin dependent diabetes; Medicinal plant; Vertebrata; Alkaloid; Chemotherapy; Hypoglycemic agent; Mammalia; Treatment; Mouse; Dicotyledones; Animal; Angiospermae; Spermatophyta; Glycemia
• ISSN: 0742-3071; 1096-9136; 1464-5491
• DOI: 10.1002/(SICI)1096-9136(199805)15:5<367::AID-DIA576>3.0.CO;2-G

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 usful drug for the treatment of Type 2 DM. © 1998 John Wiley & Sons, Ltd.