Ethnopharmacological Discovery and Preclinical Development of Anti-Malarial Lead Compounds from Medicinal Plants of the Sambisa Forest Fringe Communities, Borno State

The forest fringe communities of the Sambisa area in Borno State, North East Nigeria, represent an ecologically distinct and pharmacognostically unexplored zone where conflict-affected populations have maintained robust traditional medicine practices for malaria management in the near-complete absence of formal healthcare infrastructure. This PhD research undertakes the first systematic ethnopharmacological documentation and preclinical anti-malarial lead compound development from medicinal plants used in these communities. Ethnopharmacological surveys were conducted under humanitarian research protocols with conflict-sensitive methodology across eight accessible communities in Gwoza and Konduga local government areas, involving 66 traditional healers and community elders. Voucher specimens were authenticated at the University of Maiduguri Herbarium. The ten most-cited plant species were subjected to bioassay-guided fractionation targeting P. falciparum 3D7 and Dd2 strain inhibition. Lead fractions were advanced through a structured preclinical development pipeline including: dose-response antiplasmodial evaluation, parasite transcriptomics under compound challenge, cytotoxicity selectivity profiling, preliminary pharmacokinetic assessment in mice, and in vivo efficacy in the Peters four-day test and Rane's curative test. From 52 documented plants, Guiera senegalensis, Combretum aculeatum, and Terminalia avicennioides were identified as priority species. A novel tetracyclic terpenoid from Guiera senegalensis demonstrated IC50 of 41 nM against Dd2 and an in vivo suppression rate of 81.4% at 200 mg/kg. Parasite transcriptomics indicated apicoplast targeting as a novel mechanism. Keywords: malaria, Sambisa forest, Borno State, ethnopharmacology, preclinical development