In vitro genotoxicity of the West African anti-malarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine.
Cryptolepine (CLP), the major alkaloid of the West African anti-malarial herbal Cryptolepis sanguinolenta (Periplocaceae) is a DNA intercalator that exhibits potent toxicity to a variety of mammalian cells in vitro. We have hypothesized that the DNA intercalating properties of cryptolepine could trigger genetic damage in mammalian cells. The objective of the present study was therefore to assess the ability of both cryptolepine (CLP) and the traditional anti-malarial formulation, the aqueous extract from the roots (CSE) to induce mutation at the hprt locus and micronuclei (MN) formation in V79, a Chinese hamster fibroblast cell line commonly used in genetic toxicity studies. CSE at a high concentration (50 microg/ml) induced an apparent significant ten fold increase in mutant frequency compared to vehicle control (mean of 38 versus 4 mutant clones/10(6) surviving cells) but, this concentration of CSE was very toxic (<15% cell survival). CLP did not appear to be mutagenic in the dosage range used (up to 2.5 microM, equivalent to 1.1 microg/ml). However, after 24h treatment of V79 cells both CSE and CLP induced a dose-dependent increase in micronuclei of 4.15% and 6.43% (25 microg/ml CSE and 2.5 microM, equivalent to 1.1 microg/ml CLP, respectively) compared to 0.36% in vehicle control. These results show that treatment of mammalian cells with CSE and CLP can lead to DNA damage and we suggest that the routine use of CSE and the potential use of CLP derivatives in malaria chemotherapy could carry a genotoxic risk.
Ansah
Charles
C
Molecular Toxicology, Division of Biomedical Sciences, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Khan
Ayesha
A
Gooderham
Nigel J
NJ
D000349:Africa; D000470:Alkaloids / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D031106:Cryptolepis / Q000633:toxicity*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids; D007211:Indoles / Q000008:administration & dosage / Q000633:toxicity*; D007364:Intercalating Agents / Q000633:toxicity*; D008519:Medicine, Traditional; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity; D018517:Plant Roots / Q000633:toxicity; D011804:Quinolines / Q000008:administration & dosage / Q000633:toxicity*
D000470:Alkaloids; D000962:Antimalarials; D026121:Indole Alkaloids; D007211:Indoles; D007364:Intercalating Agents; D010936:Plant Extracts; D011804:Quinolines; C024015:cryptolepine