Anti-inflammatory drug discovery from medicinal plants: from molecular targets to therapeutic paradigms

Chronic inflammation is a central driver of diverse human diseases, including autoimmune, metabolic, neurodegenerative, and cardiovascular disorders. Although current anti-inflammatory therapies have substantially improved disease control, important unmet needs remain because of incomplete or variable responses, long-term safety concerns, high costs for some targeted treatments, and substantial interpatient heterogeneity. Medicinal plants provide a rich source of structurally diverse bioactive compounds that may offer complementary opportunities for modulating complex inflammatory processes. In this review, we discuss anti-inflammatory drug discovery from a mechanism-to-translation perspective, integrating chemical identity and active forms, proximal or direct molecular targets, the strength of target-engagement evidence, pharmacologically relevant exposure, disease-relevant mechanisms, and clinical maturity. Predicted or downstream effects are considered separately from direct target engagement and from evidence obtained in patients. We further examine emerging strategies for the discovery, mechanistic validation, and translational development of these compounds. This review outlines the main opportunities and barriers to translating plant-derived anti-inflammatory compounds into clinically useful therapies.