Genus Cucumis: Traditional uses, phytochemistry, pharmacology, clinical application, and toxicology.

The genus Cucumis L. (Cucurbitaceae), flourishes across temperate, tropical, and subtropical regions. Species within the genus have a long-standing history in traditional ethnomedicinal practices throughout Asia and Africa, addressing a wide spectrum of ailments, including gastrointestinal, metabolic, urogenital, hepatic, dermatological, cardiovascular, respiratory, inflammatory, and infectious disorders. Despite this extensive traditional use, the full therapeutic potential of Cucumis remains underexplored. This review comprehensively explores the traditional ethnomedicinal applications, phytochemical composition, pharmacological activities, clinical evidence, and toxicological profiles of Cucumis species. A systematic survey of internationally recognized scientific databases and authoritative repositories, including Web of Science, Scopus, PubMed, ScienceDirect, and Google Scholar, and revealed over 428 bioactive compounds spanning through diverse phytochemical classes. These classes include steroids, triterpenoids (predominantly cucurbitacins), flavonoids (particularly C,O-glycosylflavones), coumarins, other phenolics, and additional secondary metabolites. Collectively, these compounds demonstrate multifaceted bioactivities, encompassing anti-inflammatory, antihypertensive, anti-diabetic, anti-cancer, organ-protective, antimicrobial, and antiviral properties, as validated through in vitro, in vivo, and limited clinical studies. Nonetheless, the molecular mechanisms underpinning these pharmacological effects remain inadequately elucidated. By integrating traditional ethnomedicinal knowledge with contemporary research approaches, this review highlights the necessity of advancing scientific insight into the genus Cucumis and its bioactive constituents. Future research should focus on comprehensive phytochemical profiling, mechanistic elucidation, clinical evaluations, and rigorous toxicological assessments to ensure the safe and effective application of various Cucumis species in modern herbal medicine.