Traditional Use, Phytochemistry, and Pharmacological Potential of Centaurea Genus: A Systematic Review.

Centaurea is a large genus of approximately 700 species, predominantly distributed across the Mediterranean region and Western Asia, that has been empirically used since ancient times for metabolic, inflammatory, hepatic, infectious, and neurological disorders. This systematic review was conducted according to PRISMA 2020 guidelines. A total of 574 eligible studies published between 1955 and 2025 were retrieved from PubMed, SciFinder, and Web of Science. Included studies covered traditional knowledge, phytochemistry, in vitro and in vivo pharmacology, toxicity, and formulation techniques. Centaurea species demonstrate significant phytochemical diversity, especially sesquiterpene lactones, flavonoids, phenolic acids, lignans, and essential oils, which support their antioxidant, antimicrobial, anti-inflammatory, cytotoxic, anticholinesterase, and hepatoprotective properties. Special emphasis-including molecular identification tools, modern extraction technologies, and metabolomics-has enhanced mapping chemical complexity, with modern bioassay platforms revealing its polypharmacology, formulation strategies, and remediation approaches. However, heterogeneity in extraction methods, assay systems, and reporting standards contributes to conflicting findings and limits comparability across studies. Structure-activity relationships indicate that α-methylene-γ-lactone moieties, hydroxylated phenolics, and terpenoids are key compounds of bioactivity. Although Centaurea holds strong potential for pharmaceutical development, standardized protocols and rigorous translational research are emerging to address methodological inconsistencies, incomplete toxicological data, and the lack of clinical validation.