Dual-functional chitosan nanoparticles enhance berberine bioavailability and alleviate mastitis-associated Staphylococcus aureus infection via synergistic antioxidant and antibacterial mechanisms

초록

Bovine mastitis represents a major economic and clinical burden for the dairy industry. Because first-line treatment relies on heavy antibiotic use, it contributes significantly to the global crisis of antimicrobial resistance (AMR). There is a clear need for non-traditional therapeutics capable of reducing bacterial burden while simultaneously mitigating the inflammation and oxidative stress associated with the disease. In this study, we developed a multifunctional nanoplatform by encapsulating berberine (BBR) within gallic acid-grafted chitosan nanoparticles (GA-g-CSNPs). Covalent grafting of gallate was used to enhance the antioxidant and antibacterial properties of the chitosan backbone. Molecular docking and dynamics simulations suggested that BBR formed stable interactions with hub proteins involved in mastitis-related inflammation. These interactions may partly explain its multitarget pharmacological effects. The BBR@GA-g-CSNPs demonstrated significantly enhanced antibacterial and antioxidant activity compared with free BBR, reducing the bacterial inflammatory response in bovine mammary epithelial cells (BMECs). The nanoplatform reinforced the compromised blood-milk epithelial barrier by restoring the E-cadherin/β-catenin junctional complex. At the cellular level, the system promoted mitochondrial homeostasis by enhancing PINK1/p62-mediated mitophagy and facilitating the targeted clearance of damaged mitochondria under oxidative injury. Our findings establish BBR@GA-g-CSNPs as a viable candidate for mastitis intervention. By coupling direct bacterial suppression with the restoration of cellular quality control mechanisms, this engineered nanoplatform provides a practical strategy for mammary tissue repair, and an alternative to conventional antibiotic reliance. © 2026 Elsevier B.V.

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