Formononetin (FMN) is a naturally occurring isoflavonoid. It has been extensively researched for its therapeutic properties in neurological disorders, cancer, renal dysfunction, and inflammatory diseases, as demonstrated by both in vivo and in vitro studies. The compound is primarily obtained from plants such as Trifolium pratense (red clover) and Astragalus membranaceus. A number of clinical trials have also emphasized its function in enhancing vascular health, bone mineral content, and glucose metabolism. Formononetin has good pharmacokinetics, with rapid oral absorption, a maximum plasma concentration between 30 and 60 min, and a half-life of approximately 2 h. It is regulated by the liver through cytochrome P450 enzymes and phase II conjugation. In addition, the therapeutic action of formononetin has been found to be improved in various models when either its derivatives are formed or when it is combined with other drugs. This review article aims to comprehensively examine the pharmacological potential of formononetin across disease models while highlighting recent advances in its pharmacokinetics and safety profile. Recent developments in nanoformulation and chemical modification have been encouraging in improving its bioavailability and therapeutic efficacy. Further exploration into next-generation delivery systems such as nanoparticles and phospholipid complexes, along with combination therapies and derivative synthesis, may significantly enhance formononetin's clinical applicability. Additionally, comprehensive toxicological evaluations to establish its long-term safety in diverse patient populations are warranted.
Keywords: Derivatives of formononetin; Formononetin; Herbal sources of formononetin; In vitro and in vivo studies of formononetin; Isoflavonoid; SAR of formononetin.
© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.