EVALUATION OF THE ANTIPLASMODIAL POTENTIAL AND SAFETY OF COMBINED OF COMBINED ALCHORNEA CORDIFOLIA AND ENANTIA CHLORANTHA EXTRACTS AGAINST PLASMODIUM FALCIPARUM PLASMEPSIN II USING IN SILICO AND IN VIVO APPROACHES

Plasmodium falciparum malaria, contributing 26.8% of global malaria deaths in 2022, drives Nigeria's health burden, with artemisinin resistance necessitating novel natural product-derived treatments. This study bridges Nigeria's ethnobotanical heritage with modern pharmacognosy to evaluate the extracts of Alchornea cordifolia (Ogwu obi) and Enantia chlorantha (Awopa). This study aims to assess the antiplasmodial potential of a combined A. cordifolia and E. chlorantha extract via molecular docking against P. falciparum Plasmepsin II and evaluate its acute toxicity in mice. Leaves of A. cordifolia and stem bark of E. chlorantha were extracted with methanol, freeze-dried, and concentrated using a rotary evaporator at 40℃, respectively. Molecular docking targeted Plasmepsin II (PDB ID: 1LEE) using PyRx 0.9.8, with dihydroartemisinin (standard antimalarial drug) and R36 (co-crystallized ligand) as comparators. Compounds with binding affinities ≤ -6.5 kcal/mol were prioritised. Acute toxicity was assessed in Swiss mice using Lorke's method (10–5000 mg/kg). Drug-likeness was evaluated via SwissADME 2025.2 and ProTox-3.0. Binding affinity trends were analysed descriptively. Docking revealed 10 A. cordifolia compounds (e.g., CID:236432, -9.1 kcal/mol) and 15 E. chlorantha compounds (e.g., CID:91710667, -8.6 kcal/mol) with binding affinities ≤ -6.5 kcal/mol, comparable to dihydroartemisinin (-7.1 kcal/mol) and R36 (-10.0 kcal/mol), indicating strong Plasmepsin II inhibition. No toxicity was observed at a dose of 5000 mg/kg. Most compounds showed favourable drug-likeness.