In vitro antiplasmodial and cytotoxicity activities of crude extracts and major compounds from Goniothalamus lanceolatus

Abstract

Ethnopharmacological relevance: Malaria, a devastating infectious disease which was initially recognized as episodic fever, is caused by parasitic protozoan of the genus Plasmodium. Medicinal plants with ethnobotanical information to treat fever and/or malaria has been the key element in identifying potential plant candidates for antimalarial screening. Goniothalamus lanceolatus Miq. (Annonaceae) is used as a folk remedy, particularly to treat fever and skin diseases.

Aim of the study: In this context, supported with previous preliminary data of its antiplasmodial activity, this study was undertaken to determine the in vitro antiplasmodial and cytotoxicity activities of G. lanceolatus crude extracts and its major compounds.

Materials and methods: The in vitro antiplasmodial activity was determined by parasite lactate dehydrogenase (pLDH) assay on chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. The cytotoxicity activity was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on hepatocellular carcinoma (HepG2) and normal liver (WRL-68) cell lines.

Results: The root methanol extract possessed potent antiplasmodial activity against both P. falciparum 3D7 and K1 strains (IC₅₀ = 2.7 μg/ml, SI = 140; IC₅₀ = 1.7 μg/ml, SI = 236). Apart from the DCM extract of stem bark and root that were found to be inactive (IC₅₀ > 50 μg/ml) against 3D7 strain, all other tested crude extracts exhibited promising (5< IC₅₀ < 15 μg/ml) to moderate (15< IC₅₀ < 50 μg/ml) antiplasmodial activity against both strain. Additionally, only compound C (Parvistone D) exerted promising antiplasmodial activity against 3D7 strain (IC₅₀ = 7.5 μM, SI = 51) whereas compound A, B and D showed moderate antiplasmodial activity against the same strain (20 < IC₅₀ < 100 μM). Interestingly, when tested on K1 strain, compound A, C and D exhibited promising antiplasmodial activity (2 < IC₅₀ < 20 μM) while compound B exhibited moderate activity (IC₅₀ = 26.9 μM). Cytotoxicity study showed that all tested crude extracts and compounds were non-toxic on WRL-68 and HepG2 cell lines (CC₅₀ > 30 µg/ml, CC₅₀ > 10 µM, respectively), except for the hexane and DCM extracts of root, which exerted mild cytotoxicity on HepG2 cell line (IC₅₀ < 30 μg/ml).

Conclusions: This study suggests that the root methanol extract and compound C (Parvistone D) obtained from G. lanceolatus are highly potential for exploitation as source of antimalarial agents. Parvistone D is identified as one of the bioactive styryl lactones found in the plant extract. It is also noteworthy, that the extract and compound were more active against chloroquine-resistant (K1) strain of P. falciparum. Further studies are being carried out to assess their toxicity profile and antimalarial efficacy in animal model.

Keywords: Antiplasmodial activity; Cytotoxicity; Goniothalamus lanceolatus; Plasmodium falciparum; Styryl lactones.