Grifolin Exhibits Promising Antimicrobial Potential Against MRSA Infection

Methicillin-resistant Staphylococcus aureus (MRSA) exhibits widespread multidrug resistance and frequently causes refractory wound infections, particularly in diabetic patients, creating an urgent need for new therapeutic options. Grifolin, a naturally occurring phenolic compound with antibacterial, anti-inflammatory, and antioxidant activities, represents a promising candidate for the comprehensive treatment of infected diabetic wounds. Herein, we systematically investigated the antibacterial activity and mechanism of grifolin against MRSA, as well as its therapeutic efficacy in a murine model of MRSA-infected diabetic wounds. In vitro, grifolin exhibited potent antibacterial activity against MRSA (MIC = 3 μg/mL, MBC = 4 μg/mL), effectively eliminated mature biofilms, and potentiated conventional antibiotics. Integrated transcriptomic and proteomic analyses, corroborated by qRT-PCR, revealed coordinated changes in membrane integrity, translation and metabolism, and quorum sensing and virulence. In vivo, grifolin significantly reduced the wound bacterial burden, suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, promoted angiogenesis and tissue remodeling, and accelerated diabetic wound healing with favorable preliminary tolerability. This study highlights grifolin as a promising lead compound for combating MRSA infections and treating associated diabetic wound complications.