Theoretical Framework for Indigenous Knowledge Integration in Pharmaceutical Chemistry Drug Discovery: A Critical Analysis of Yoruba Ethnomedical Practice in South West Nigeria

The systematic integration of indigenous knowledge systems into pharmaceutical chemistry drug discovery pipelines has been proposed as a strategy to accelerate hit identification from biodiversity-rich regions. However, existing frameworks largely privilege Western ontological approaches to evidence hierarchy, marginalising the epistemological validity of traditional knowledge systems like Yoruba ethnomedical practice in South West Nigeria. This study developed and validated a theoretical framework for ethnomedical knowledge integration that preserves indigenous conceptual integrity while meeting pharmacological scientific standards. A grounded theory approach guided data collection through ethnographic fieldwork with traditional medicine practitioners across Osun, Ekiti, Ondo, and Ogun States. Framework development drew on critical epistemology, decolonial theory, and existing ethnopharmacological validation models. The proposed Integrated Ethnomedical Pharmacological Framework distinguishes three validation tracks: empirical-pharmacological, contextual-ethnographic, and systems-ecological, allowing parallel rather than sequential knowledge translation. Criteria for prioritising disease-plant associations for pharmacological investigation were developed using Bayesian probability weighting of ethnopharmacological consensus indices. A pilot application of the framework to 120 Yoruba plant-disease associations identified twelve high-priority candidates for pre-clinical investigation. The framework was critically evaluated by both traditional medicine practitioners and pharmaceutical scientists through structured consultations. This study contributes an original theoretical contribution to the field by offering a pluralistic epistemological foundation for indigenous knowledge-led drug discovery in the Nigerian context. Keywords: ethnopharmacology, indigenous knowledge, Yoruba medicine, drug discovery framework, South West Nigeria.