Silybum marianum against multidrug-resistant bacterial pathogens: mechanisms of action, synergistic therapy, nanoformulations, and clinical translation.

Silybum marianum, commonly known as milk thistle, has a long history of medicinal use as a hepatoprotective plant and has emerged as a potential source of natural antimicrobial agents against multidrug-resistant (MDR) bacterial pathogens. This review provides an objective overview of current knowledge on the antimicrobial mechanisms of S. marianum and its potential utility for targeting resistant bacterial strains. Recent studies have demonstrated that silymarin, the major flavonolignan complex isolated from the seeds of S. marianum, exhibits observable antimicrobial activity against several critical MDR phenotypes, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, carbapenem-resistant Klebsiella pneumoniae, and Stenotrophomonas maltophilia. The antimicrobial effect of silymarin is concentration-dependent, with ethanolic extracts exhibiting greater antibacterial activity than aqueous extracts. The principal mechanisms underlying the anti-MDR activity of S. marianum include multiple pathways: disruption of bacterial membranes, increasing permeability; inhibition of biofilm formation; modulation of reactive oxygen species; inhibition of efflux pumps; and synergistic enhancement of conventional antibiotic activity. Advanced nanoformulation techniques have been applied to address the poor baseline bioavailability of silymarin, with nano-silymarin systems displaying lower minimum inhibitory concentrations (MICs) than conventional formulations against clinical MDR isolates in laboratory models. Topical delivery systems, such as mucoadhesive gels, offer sustained drug release profiles and enhanced permeation properties. Nevertheless, standardising extraction protocols, optimising dosing regimens, and conducting rigorous clinical trials remain essential steps to translate these preclinical findings into viable human therapeutic applications.