The Perspectives of Combining Antibiotics with Saponins-Herbal Excipients

The overuse of antibiotics in human and veterinary medicine has contributed significantly to their persistent presence in the environment, creating conditions that promote the spread of antimicrobial resistance (AMR). In this context, innovative approaches that reduce antibiotic doses without compromising therapeutic efficacy are urgently needed. This review explores the emerging role of plant-derived secondary metabolites, particularly saponins, as bioactive excipients capable of enhancing antibiotic activity through synergistic mechanisms. By improving membrane permeability, inhibiting resistance pathways, and modulating host responses, these natural adjuvants may allow for lower antibiotic concentrations in clinical treatments, ultimately reducing pharmaceutical residues entering the environment. We discuss the potential of such combined therapies not only to mitigate the evolution and dissemination of AMR in natural microbial communities but also to provide more sustainable, biodegradable, and ecologically safer alternatives to synthetic formulation agents. Plant-derived compounds, inherently shaped by co-evolution with microbes, offer a dynamic and adaptive molecular diversity that may be less prone to long-term microbial resistance. In addition to reviewing current knowledge, this article highlights the environmental and public health implications of integrating phytochemical excipients into antibiotic regimens, and calls for further interdisciplinary efforts to evaluate their safety, efficacy, and role in shaping future antimicrobial stewardship.