Exploring the Genus Ruta: Traditional Uses, Pharmacology, and Safety Concerns

Rue (<i>Ruta</i> spp.) is a medicinal, ornamental, and culinary herb, distinguished by its strong repellent aroma, rich in various bioactive compounds. In addition to different traditional uses, rue shows anti-inflammatory, anticancer, antiviral, and antifungal properties. Thus, we aimed to comprehensively review the past and present roles of <i>Ruta</i> spp. in the management of diseases. Accordingly, we systematically reviewed PubMed, Web of Science, Scopus, and Cochrane Library with relevant keywords for ethnopharmacological, pharmacological, pre-clinical, clinical, and toxicological studies to evaluate the efficacy and safety of rue, in addition to its traditional applications. In traditional Indian and Persian Medicine, rue is mostly utilized for tonifying the stomach, managing neural complications, and regulating the menstrual cycle. Ethnopharmacological studies indicated that all parts of rue are used in more than 15 countries for different purposes such as for the diseases of respiratory system, urinary system, gastrointestinal system, and nervous system. In preclinical studies, <i>Ruta</i> spp. are examined in the management of neurologic disorders, endocrine and metabolic disorders, gastrointestinal disorders, and neuropsychologic disorders. Human studies mainly included homeopathic formulations in musculoskeletal disorders, oncology, ophthalmology, obesity, and gynecology. Although <i>Ruta</i> spp. show antioxidant effects, their systemic toxicity, cytotoxicity, and photosensitivity effects may be related to the bioactive compounds such as xanthotoxin, psoralenes, and bergapten in high doses. In conclusion, in the usual dose that is used, rue showed the potential of managing different health problems; however, more clinical studies are required.