Isolation and Characterization of Antiplasmodial Secondary Metabolites from Medicinal Plants in Niger State, Nigeria

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Isolation and Characterization of Antiplasmodial Secondary Metabolites from Medicinal Plants in Niger State, Nigeria.

Abstract: Malaria remains a significant global health challenge due to the development of resistance in malaria parasites against most existing anti-malarial drugs. To address this issue, exploration of medicinal plants for novel bioactive compounds with antiplasmodial potential and high safety margins is of great interest. In this study, we focused on eight medicinal plants: Agelanthus dodoneifolius, Securidaca longepedunculata, Neocarya macrophylla, Merremia hederacea, Zanthoxylum zanthoxyloides, Leptadenia hastata, Polycarpea linearfolia, and Lophira alata, collected from Niger State, Nigeria. Methanol extracts of these plants underwent phytochemical screening and acute toxicity testing using standard methods. The extracts were then evaluated for antiplasmodial activity against both chloroquine-sensitive (CQS) strain NF54 and chloroquine-resistant strain (CQR) K1 of Plasmodium falciparum in vitro, as well as against CQS (NPK) strain of Plasmodium berghei in vivo at doses of 100, 200, and 400 mg/kg bw.

The subchronic toxicological screening of the most active extracts, namely P. linearfolia and L. hastata, was carried out orally in rats at a dose of 200 mg/kg bw for 28 days. Biochemical and hematological parameters were monitored, and histopathological examination of the liver, kidney, heart, and spleen was performed in both test animal and control groups. The most active extracts in vivo were subjected to bioassay-guided fractionation, and active compounds were characterized using 1H NMR, 13C NMR, and HPLC-ESI/MS.

The plant extracts were found to contain various phytochemicals, with the exception of phytosteroids, which were absent in A. dodoneifolius. The acute toxicity study revealed that P. linearfolia had the highest safety margin with an LD50 value of 4500 mg/kg bw. Among the tested extracts, Z. zanthoxyloides demonstrated the highest in vitro inhibition against CQS and CQR strains, with IC50 values of 1.07 and 1.31 µg/ml, respectively. In the in vivo activity assessment, the parasite density of L. hastata (576 parasites/µl) and P. linearfolia (473 parasites/µl) at 400 mg/kg bw were comparable to the standard control (431 parasites/µl). The mean survival time of the L. hastata and P. linearfolia treated groups ranged from 31 to 35 days, which was also comparable to the standard.

The subchronic administration of P. linearfolia and L. hastata extracts in rats resulted in some significant changes in biochemical parameters, indicating potential effects on certain physiological functions. Histopathological analysis revealed normal cell architecture in all organs, except for hyperplastic lymphoid follicles in the spleen of L. hastata treated group. Bioassay-guided fractionation of the most active extracts led to the identification of two antiplasmodial compounds: 2,2’–methylene bis(6-tert-butyl-4-methylphenol) and Sclerinone A in P. linearfolia extract, and 2,2’–methylene bis(6-tert-butyl-4-methylphenol) in L. hastata.

These identified antiplasmodial agents have the potential to serve as templates for the development of new antimalarial drugs that can target both chloroquine-sensitive and resistant strains of Plasmodium falciparum. This research opens up new possibilities for combating malaria and alleviating its global burden.

Isolation and Characterization of Antiplasmodial Secondary Metabolites from Medicinal Plants in Niger State, Nigeria.

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