The Popular Herbal Antimalarial, Extract of Cryptolepis sanguinolenta, Is Potently Cytotoxic

Abstract

The aqueous root extract of Cryptolepis sanguinolenta (CSE) is a popular antimalarial in West African ethnomedicine. Cryptolepine (CLP), the major alkaloid of the plant, is a cytotoxic DNA intercalator that has promise as an anticancer agent. To date the aqueous root extract, the traditional antimalarial formulation, has not been evaluated for toxicity. In this study, we have examined the in vitro toxicity of CSE and CLP using V79 cells, a Chinese hamster lung fibroblast frequently used to assess genetic toxicity, and a number of organ-specific human cancer cell lines. CSE and CLP caused a dose- and time-dependent reduction in viability of the V79 cell line. Flow cytometric analysis of CSE- and CLP-treated (24 h) asynchronously growing V79 cells using propidium iodide (PI) staining revealed an accumulation of cells (up to 55%) in the sub-G1 phase of the cell cycle, indicative of cell death. The V79 cells and almost all the organ-specific human cancer cell lines exposed to CSE and CLP were profoundly growth inhibited, as measured in a clonogenicity assay. In a V79 cell mutation assay (hprt gene), CSE (5-50 microg/ml) only induced mutation at the highest dose employed (mutation frequency approximately 4 and 38 mutant clones per 10(6) cells for control and CSE, respectively), but CLP (0.5-5.0 microM) was not mutagenic. These results indicate that CSE and CLP are very cytotoxic and may be weak mammalian mutagens and/or clastogens. The poor genotoxicity of CSE and CLP coupled with their potent cytotoxic action support their anticancer potential.

Design and In Vitro Haemolytic Evaluation of Cryptolepine Hydrochloride-Loaded Gelatine Nanoparticles as a Novel Approach for the Treatment of Malaria

“…The presence of basicity has long been known to influence the ability of the quinolines to accumulate in the acidic food vacuole of the plasmodium parasite where they exert their activity (8,9). Though the antimalarial activity of cryptolepine hydrochloride is not in doubt, it has been reported to be potentially cytotoxic (6,10,11). A number of synthetic strategies have been carried out in an attempt to improve the antimalarial capability of cryptolepine and reduce its DNA intercalation property (5,12,13), but there are limited reports on the use of formulation strategies to improve the profile of the compound (14).…”

Synthesis of novel halogenated cryptolepine analogues

“…Cryptolepine and its derivatives present a large spectrum of biological activities which include antimicrobial, antibacterial, anti-inflammatory, antihypertensive, antipyretic, antimuscarinic, antithrombotic, noradrenergic receptor antagonistic and vasodilative properties [1]. Cryptolepine also possesses significant antiplasmodial activity [2] and as the major alkaloid of the plant, is a cytotoxic DNA intercalator that has promise as an anticancer agent [3]. Cryptolepine is a rare example of a natural product where synthesis was reported prior to its isolation from nature.…”

Characterisation of fatty acids in the roots of Cryptolepis sanguinolenta

“…In the in vitro toxicity analysis of the aqueous extract of C. sanguinolenta using V79 cells, a Chinese hamster lung fibroblast frequently used to assess genetic toxicity and a number of organ-specific human cell lines, the aqueous extract caused a dose-and time-dependent reduction in viability of the V79 cell line. Cryptolepine, the major alkaloid of the plant and in the antimalarial decoction, is a cytotoxic DNA intercalator and a potential anticancer agent [5].The traditional antimalarial decoction is prepared either by boiling the powder of the root in water for about two hours and strained or by maceration with ethanol in a preparation popularly called 'Bitters' in Ghana. The preparation methods of the antimalarial decoction are such that fatty acids esters are also extracted into the decoction.…”

“…Schlechter (Asclepiadaceae) [4,6,7]. Unlike the alkaloids, not much attention has been given to the study of fatty acids of C. sanguinolenta inspite of the high patronage of the plant as an antimalarial in Ghana and the West African subregion and the risk its fatty acids constituents could pose to consumers as the cause of many ailments such as heart diseases, stroke, diabetes, and hypertension [5].Exhaustive extraction of the root of the plant with petroleum ether 40-60qC provided a pale yellow oil of 3.8 g (0.7%) to the wet mass of raw material as compared to the usually dark-red syrup of the total alkaloidal extract of 5.5% [1]. The small amount of the oil in the plant might be the reason why fatty acids of the plant have received little or no attention, resulting in the paucity of information on the fatty acids constituents in the plant.…”

“…In the in vitro toxicity analysis of the aqueous extract of C. sanguinolenta using V79 cells, a Chinese hamster lung fibroblast frequently used to assess genetic toxicity and a number of organ-specific human cell lines, the aqueous extract caused a dose-and time-dependent reduction in viability of the V79 cell line. Cryptolepine, the major alkaloid of the plant and in the antimalarial decoction, is a cytotoxic DNA intercalator and a potential anticancer agent [5].…”