Verbascoside from Acanthus montanus (Nees) T. Anderson (Acanthaceae) inhibits malaria proteins PfDHFR-TS and plasmepsin II: an experimental and computational approach

Malaria is one of the leading causes of death in Africa. This study investigated the antiplasmodial activities of hydroethanolic extract of Acanthus montanus (Nees) T. Anderson whole plant and isolated compound. Hydroethanolic extract of A. montanus whole plant obtained by percolation for 72 h at room temperature was fractionated using vacuum liquid chromatography, repeated accelerated gradient chromatography on silica gel and Sephadex LH 20 columns and recrystallization methods to afford Compound 1 which was elucidated by analysis of ¹H-NMR, ¹³C-NMR, DEPT-135, COSY, HMQC, HMBC, and HRESIMS data and comparison with literature data. The antiplasmodial activity was carried out using a 4-day chemosuppresive and curative assays. The computational interaction of Compound 1 was investigated against Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) and Plasmepsin II. Spectra analysis revealed Compound 1 to be Verbascoside. The antiplasmodial activity of the crude extract, acetone fraction, and Compound 1 on early, and established malaria infections increases as the dose levels increase. The crude extract, and acetone fraction at a 400 mg/kg dose exhibited 37.83%, and 41.57% parasite suppression respectively, while Compound 1 at 5 and 10 mg/kg respectively showed 48.65% and 61.19% reduction of the parasitemia level of infected mice, as against chloroquine at 10 mg/kg with a chemosuppresive activity of 91% in the 4-day chemosuppresive test. In the curative test, 1, exhibited parasitemia clearance of 42.96% and 49.55% at 5 and 10 mg/kg respectively. The computational analysis showed that 1 elicited good binding energies against Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (− 9.4 kcal/mol) and plasmepsin II (− 8.2 kcal/mol) as against chloroquine standard antimalarial drug with − 7.2 kcal/mol and − 6.4 kcal/mol respectively. This study showed that A. montanus and verbascoside have promising antiplasmodial activity, thereby justifying the ethnomedicinal use of the plant against malaria.