Ruta graveolens L. in Evidence-Based Phytotherapy: Pharmacological Activities, Bioactive Compounds and Safety

Ruta graveolens L. is widely used in traditional European, Asian, African, and South American medicine for digestive, nervous, cardiovascular, respiratory, and reproductive disorders. Despite its long-standing ethnomedical relevance, the translation into evidence-based phytotherapy remains limited due to fragmented pharmacological data and well-documented safety concerns. This review critically synthesizes ethnomedical use, phytochemical composition, pharmacological activities, and toxicological risks of R. graveolens, aiming to evaluate its therapeutic potential and identify key research gaps. A systematic search and critical analysis were conducted following PRISMA guidelines using PubMed, ScienceDirect, and Google Scholar. Ethnomedicinal data were reviewed without time limits, while phytochemical and pharmacological studies published between 2014 and 2025 were analysed in detail. More than 160 compounds (including furanocoumarins, alkaloids, flavonoids, and others) have been identified by HPLC, CC, GC-MS, and NMR methods, of which 38 are characteristic markers. The plant exhibits a wide spectrum of activity, from antimicrobial to antitumor. However, due to the content of furanocoumarins and alkaloids, the extracts have phototoxic, abortifacient, hepatotoxic, and nephrotoxic effects, which highlights safety concerns in the absence of dosage control. Although R. graveolens represents a chemically diverse source of bioactive compounds with promising pharmacological potential, its integration into modern phytotherapy requires rigorous toxicological evaluation, extract standardization, and well-designed preclinical and clinical studies. Future research should prioritize development of standardized extracts with defined phytochemical profiles, comprehensive dose-dependent toxicological assessment, and translational studies bridging experimental findings with clinical applications with particular attention to safe therapeutic windows and less toxic bioactive constituents.