A comprehensive review on plant-derived bioactive saponins as promising antimicrobial agents: from bioavailability challenges, molecular mechanistic insights to therapeutic applications.

A major worldwide health concern is antimicrobial resistance (AMR), driving an urgent need for novel therapeutic agents. Saponins, glycosylated phytochemicals with amphiphilic structures, have emerged as promising candidates owing to their wide-ranging antimicrobial effects. These substances exhibit potent antibacterial activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus, and antifungal activity against pathogens like Candida and Trichophyton species. Furthermore, saponins demonstrate potential in combating viral diseases, attributed to their ability to disrupt lipid membranes and modulate host immune responses. Recent advances in saponin research highlight innovations in extraction techniques, formulation strategies, and combination therapies, enhancing their bioavailability and therapeutic potential. Computational studies have further elucidated their mechanisms of action, supporting the development of saponin-based drug delivery systems and synergistic applications with existing antimicrobials. With their structural diversity, bioactivity, and versatility in medical, agriculture, and biotechnology applications, saponins represent a critical natural resource for addressing the AMR crisis and advancing future antimicrobial therapies. Therefore, this review aims to comprehensively summarize recent findings on the antimicrobial properties of plant-derived saponins, clarify their mechanisms of action, bioavailability challenges, and highlight their therapeutic potential and future directions.