Dual-functional berberine-magnolol co-assembled nanoparticles inhibit Fusarium graminearum growth and mycotoxin production.

Fusarium graminearum, a major fungal pathogen of cereal crops, causes severe yield losses and widespread contamination with deoxynivalenol (DON), a heat-stable and persistent mycotoxin that threatens food safety and human health. F. graminearum has developed resistance to single-target azole fungicides, necessitating the development of multi-target antifungal agents. Inspired by the synergistic effects occurring in traditional herb pairs, we report that eco-friendly berberine (BBR)-magnolol (MN) co-assembled nanoparticles (B-M NPs), prepared without synthetic surfactants, exhibit strong multipath inhibition against F. graminearum (EC = 7.0 μg/mL) and broad-spectrum antifungal activity against other plant pathogens. Scanning electron microscopy and conductivity assays revealed that B-M NPs efficiently disrupted cell membrane, leading to metabolite leakage. RT-qPCR results revealed significant downregulation of key genes involved in ergosterol biosynthesis (ERG1, ERG3) and DON production (TRI5, TRI6, TRI10), suggesting that B-M NPs interfere with both membrane integrity and metabolic pathways. Moreover, the lack of impact on CYP51 expression further indicates that the mechanism is distinct from that of traditional azole antifungals, which target CYP51, thereby overcoming azole resistance. In wheat coleoptile assays, B-M NPs reduced lesion size by 84.8 % and remarkably suppressed DON production without genotoxicity or adverse effects on wheat growth. Furthermore, this nano-fungicide is promising for the integrated management of F. graminearum and the mitigation of DON contamination in cereal crops, both pre- and post-harvest. These findings underscore the potential of this nano-fungicide for field application and commercial development in sustainable crop protection, owing to its natural origin, surfactant-free preparation, broad-spectrum antifungal activity, and favorable environmental profile.