Bioactive Phytochemical Compounds in Medicago sativa L. (Alfalfa): A Systematic Review of Biological Properties and Therapeutic Relevance in Nutraceutical and Functional Food Implications

Abstract

Medicago sativa L. (alfalfa) harbors a remarkably diverse reservoir of bioactive secondary metabolites. Flavonoids, isoflavones, and triterpenoid saponins dominate its bioactivity landscape, driving potent antioxidant, anti-inflammatory, antimicrobial, estrogenic, hypolipidemic, and cytotoxic actions through redox modulation, membrane perturbation, receptor engagement, and suppression of NF-κB/MAPK signaling. Evidence converges on multi-organ protection, improved endothelial tone and lipid profiles, neuroprotection via oxidative-stress quenching, photoprotection afforded by carotenoids and flavones, and selective antitumor effects through apoptosis induction and cell-cycle arrest. Emerging research applications, of M. sativa L. saponins include functional-food fortification, bio-emulsifier applications and sustainable crop-protection strategies. Despite these promising insights, heterogeneity in extraction protocols, lack of phytochemical standardization, and scarce pharmacokinetic or long-term safety data currently affect M. sativa L. usage. This systematic review provides a comprehensive compound-by-compound matrix linking chemical classes to their biological functions, thereby establishing a reproducible platform for targeted metabolomic, toxicological, and controlled trial investigations aimed at unlocking the biomedical and biotechnological potential of M. sativa L. phytochemicals. The novelty of this work lies in its systematic integration of all currently available phytochemicals reported in alfalfa, together with their nutraceutical and functional food implications, which extends beyond the scope of earlier reviews. By highlighting structure–activity trends and pinpointing unexplored mechanistic nodes, this review aims to accelerate M. sativa L. nutraceutical design and regulatory appraisal worldwide. © 2025 The Author(s). Food Frontiers published by John Wiley & Sons Australia, Ltd and Nanchang University, Northwest University, Jiangsu University, Zhejiang University, Fujian Agriculture and Forestry University.