Urtica dioica From El Menzel (Morocco): Phytochemical Analysis, In Vivo and In Silico Evaluation of Analgesic and Anti-Inflammatory Effects, and Toxicological Study With ADME Profiling.

Stinging nettle (Urtica dioica) remains under-characterized despite its widespread ethnomedicinal use. Here, we combine quantitative phytochemistry, validated rodent pharmacology, and multi-target molecular modeling to explore the analgesic and anti-inflammatory potential of a Moroccan ecotype. HPLC-PDA analysis of the hydro-ethanolic extract (yield 14.8%) identified 15 phenolics, dominated by chlorogenic acid (26.5%), caffeic acid (18.8%), and p-coumaric acid (12.8%). In vivo, the polyphenolic fraction (100 mg/kg, p.o.) significantly reduced acetic-acid writhing and carrageenan paw edema by 52% and 73%, respectively, and decreased both neurogenic and inflammatory phases of the formalin assay by over 59%. Similar efficacy was observed with the crude extract at 400 mg/kg, and acute oral toxicity tests showed no adverse effects up to 4 g/kg. Docking studies to mPGES-1, TRPV1, and BK2R revealed binding energies as low as -10.5 kcal/mol, highlighting rutin, hyperoside, and chlorogenic acid as promising lead compounds. ADME/Tox profiling indicated high oral developability for apigenin and a broad safety margin for all leads. Overall, these findings position U. dioica extracts as mechanistically validated phytopharmaceutical candidates for pain and inflammation management, supporting their potential for clinical development.