From Ethnobotany to Evidence: Integrative Strategies for Phytochemical Discovery and Therapeutic Translation

Abstract

Ethnobotanical knowledge has been used to discover clinically useful natural products many times, but the conversion from traditional use to documented reproducibility of therapeutic benefit is inefficient. This review presents an integrative approach that links community-based knowledge to the botanical validation, contemporary extraction, chemical characterisation, bioactivity testing, multi-omics, network pharmacology, artificial intelligence, drug formulation and clinical validation. The suggested framework sees the discovery of phytochemicals not as a linear process looking to one single active ingredient, but as a process of generation evidence in an iterative manner. Specific attention is given to surveillance and documentation of plant species and their use, orthogonal analytical confirmation, mechanism-dependent screening, mechanism-based drug pharmacokinetics and mechanism-based toxicity characterisation, and early focus on product standardisation.
Computational approaches can be useful to speed up the annotation and prioritisation process, but the predictions of these approaches should be tested experimentally and reported openly. Other factors include fit-for-purpose formulations, well-designed clinical trials, pharmacovigilance, ethical access and benefit sharing, and sourcing sustainability. Combination of all these can lead to lesser false-positive discoveries, greater reproducibility and distinguish promising phytochemicals from insufficiently characterised extracts. Thus, a coordinated link from ethnobotany to evidence may be beneficial for natural product drug discovery and for standardizing and evidence-based phytomedicines.