Pelargonium sidoides - from ethnopharmacology to evidence-based medicine: a systematic review.

BACKGROUND: Pelargonium sidoides DC. (Geraniaceae) has a long history of traditional use among indigenous peoples of Southern Africa for treating respiratory and gastrointestinal disorders. Its transformation into the modern pharmaceutical product Umckaloabo (EPs® 7630) exemplifies the transition from traditional medicine to evidence-based therapeutics. PURPOSE: To provide a systematic analysis of P. sidoides, spanning from its botanical characteristics and ethnobotanical roots to its development as a regulated phytomedicine. The review focuses on the plant's unique phytochemical profile and provides a detailed synthesis of its molecular and systems-biological mechanisms of action, cultivation sustainability, and clinical efficacy in managing respiratory tract infections. STUDY DESIGN AND METHODS: A systematic search was conducted across PubMed, Scopus, and Cochrane Library up to December 2025 following PRISMA guidelines. Sources included scientific articles, pharmacopoeias, patents, and ethnobotanical records in English and Ukrainian. RESULTS: The systematic synthesis of identified records characterizes the chemical diversity of P. sidoides, focusing on specialized metabolites such as highly substituted benzopyranones, prodelphinidins, and unique coumarin sulfates. The review discusses modern cultivation practices, sustainability issues, and comparative extraction techniques, while analytical methods such as HPLC, LC-MS, and TLC for standardization are summarized. The pharmacological profile is defined by multi-target activity, encompassing immunomodulatory, antibacterial, and antiviral effects, including studies on SARS-CoV-2 and other respiratory pathogens. Analysis of available clinical data validates the therapeutic use of P. sidoides root preparations for managing acute bronchitis, rhinosinusitis, and tonsillopharyngitis. CONCLUSION: This study demonstrates that the integration of P. sidoides into modern healthcare is supported by the synergy between traditional knowledge and molecular and clinical validation. By mapping the developmental trajectory - from wild harvesting to systems-biological evidence - this review identifies P. sidoides as a model for the pharmaceutical translation of ethnobotanical resources into standardized, evidence-based phytomedicines.