Methicillin-resistant Staphylococcus aureus (MRSA) has posed a severe global health threat. In this study, we screened an antibiotic and non-antibiotic combination that provides a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA) could synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. This synergy specifically targets MRSA and was also validated using 25 clinical MRSA strains using time–kill analysis. We speculated that the underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs). As a result, the synergistic efficiency of CDCA with carbapenems targeting PBP1 was better than that of β-lactams targeting PBPs. Moreover, we showed that CDCA did not affect the expression level of PBPs, but sensitized MRSA to carbapenems by disrupting the cell membrane. In our study, we have revealed a novel synergistic combination of antibiotics and non-antibiotics to combat potential bacterial infections.

Background: Skin barrier dysfunction leads to increased transepidermal water loss (TEWL), inflammation, and compromised skin protection. While Paeonia ostii (peony) flowers are recognized in traditional Chinese medicine for their reducing melanin synthesis, anti-inflammatory, and anti-aging effects, their role in repairing skin barrier damage has not been fully explored. Methods: We investigated the therapeutic potential of peony flower extract (PFE) in the tape-stripping-induced mouse model with skin barrier damage. Skin surface imaging, hydration measurements, H&E, proteomics, qPCR, and immunofluorescence were applied to clarify the potential mechanism of PFE in attenuating skin barrier impairment. Results: PFE significantly reduced erythema, TEWL, and edema while restoring epidermal architecture. Proteomics analysis identified cornified envelope formation and tight junction assembly as essential mechanisms in skin barrier repair. It increased the expression of key skin barrier proteins, including filaggrin (Flg), involucrin (Ivl), loricrin (Lor), claudin-1 (Cldn1), tight junction protein 1 (Tjp1), and occludin (Ocln). Conclusions: This study demonstrates that PFE restores skin barrier integrity by upregulating key structural proteins within the cornified envelope and tight junction. These findings suggest that PFE is a promising therapeutic candidate for skin barrier repair, with high potential in translational medicine applications.