Ethnomedicinal plants for pain and inflammation in Malakand Top, Pakistan: an ethnopharmacological and in silico evaluation.

Pain remains one of the most common health concerns worldwide, and medicinal plants continue to play an important role in its traditional management. This study aimed to document and evaluate medicinal plants traditionally used for pain management in the Malakand region of Pakistan using ethnopharmacological approaches. A semi-structured questionnaire survey was conducted across ten villages involving 377 informants. Ethnopharmacological indices, including Relative Frequency of Citation (RFC) and Fidelity Level (FL), were used to assess the importance of reported medicinal plants. Major phytoconstituents from the five most frequently cited species were further subjected to in silico pharmacokinetic and drug-likeness evaluation using the SwissADME web server. A total of 35 medicinal plant species belonging to 27 families were documented. Lamiaceae and Fabaceae were the most represented plant families. Dietary and topical preparations were the predominant modes of administration. The documented plants were used to treat various pain-related conditions, with arthritis (15 species) and stomachache (14 species) being the most frequently reported, followed by toothache, backache, headache, and peripheral pain. Curcuma longa exhibited the highest RFC (0.84) and FL (84.8%), followed by Acacia nilotica, Nigella sativa, Dodonaea viscosa, and Mentha spicata. SwissADME analysis suggested favorable drug-likeness profiles for curcumin, thymoquinone, quercetin, catechin, and limonene, with all compounds satisfying Lipinski's rule of five and had a predicted bioavailability score of 0.55. The BOILED-Egg model further predicted blood-brain barrier permeability for thymoquinone and limonene. The study highlights the rich ethnomedicinal knowledge of the Malakand region and identifies several promising plant species used in traditional pain management. In silico analysis provided preliminary support for the pharmacokinetic suitability of major phytoconstituents, warranting further experimental and clinical investigations. Conservation strategies are recommended to preserve these valuable medicinal resources.