Magnolol inhibits the resistance of ESBLs E. coli to fourth-generation cephalosporins in vitro and in vivo.

Yat-Ching Tong, Hui-Hsuan Lin, Yanfang Yang, Zhi-Lin Zhou, Yuanchao Zhang, Jingze Wang, W Ma, Yanling Wang, W Y Zhang, Su-Zhu Qing

Phytomedicine

Mar 1, 2026

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Abstract

BACKGROUND: Antimicrobial resistance (AMR) infection is attracting increasing attention, especially superbug infections. As a result, finding ways to reduce AMR is essential. For the time being, natural compound therapy for reducing AMR is an ideal choice. PURPOSE: This study aims to investigate the mechanism of magnolol reducing the AMR of E. coli in vitro and vivo. METHODS: The morphology and function of E. coli under magnolol treatment were assessed using a scanning electron microscope, qPCR, RNA-seq, and other methods. Moreover, the in vivo treatment effects of magnolol combined with antibiotics were evaluated by HE and IHC staining. RESULTS: In this study, we found that magnolol reduced the resistance of ESBL E. coli to the fourth-generation cephalosporin in vitro via two main mechanisms. Firstly, magnolol disrupts iron ion metabolism by increasing environmental iron uptake significantly (P≤0.01), leading to a significant increase in intracellular ROS (P≤0.01) and membrane damage. Secondly, magnolol significantly inhibits the relative mRNA expression of blaCTX-M-1 (P≤0.01) and the CTX-M-1 enzyme activity in ESBL E. coli. Furthermore, we find that magnolol can inhibit ESBL E. coli in vivo by significantly reducing the TLR4-NFκB p65 pathway (P≤0.01). CONCLUSION: In a word, our results indicate that magnolol is a natural antibacterial adjuvant with potent inhibitory activity against bacterial resistance and exerts this activity through multiple pathways, which has particular significance for the further study of the AMR mechanism.