Pharmacology of Manilkara hexandra leaf extract: potent antimalarial by targeting β-hematin formation and pro-inflammatory cytokine investigation

The renewed interest in the bioprospecting of medicinal plants to treat malaria for the endemic population at times of resistance and non-availability of expensive drugs holds importance. As a part of our ongoing bioprospection activity, the present study aimed to illustrate the antimalarial activity and pro-inflammatory cytokine-modulating effects of leaf extracts of Manilkara hexandra. The anti-plasmodial and antimalarial activities were carried out through chloroquine-resistant strain (K1) of Plasmodium falciparum and Plasmodium berghei K-173 infected mice, respectively. Further, the observations were substantiated with β-haematin formation, reactive oxygen species, and cytotoxicity. Amongst the four extracts (hexane, chloroform, ethyl acetate, and methanol), the hexane and methanol leaf extracts showed potent activity against P. falciparum with IC₅₀ values of 18.26 ± 2.38 µg/mL and 20.20 ± 3.70 µg/mL respectively. Both the extracts were found to inhibit the β-hematin formation with an IC₅₀ (91.64 ± 12.49 µg/mL and 100.00 ± 14.51 µg/mL), respectively. In addition, both extracts increased intracellular ROS levels to 84.06 ± 3.13% and 113.15 ± 6.40% at IC₅₀ concentrations compared to unexposed culture. However, in in vivo malaria in mice, the methanol extract was found to be optimum in chemo-suppression of parasitemia, pro-inflammatory cytokine-modulating effects, increased hemoglobin levels, and mean survival days at 500 mg/kg body weight. Further, most in vivo antimalarial, methanol extract did not exhibit any significant changes in the plasma biochemistry of mice in acute oral toxicity studies at 500 and 2000 mg/kg body weight. After conducting extensive tests, it has been discovered that M. hexandra is a highly effective remedy for malaria.