MiR-423-5p Targeting IKBKE Ameliorates LPS/GPS-induced Inflammation and Cross-border Regulation of Exogenous miRNAs in Scutellaria baicalensis.

Glaesserella parasuis (GPS) is responsible for Glasser's disease. The infection is contagious and systemic in nature. Pneumonia is one of its main clinical features and contributes to the development of lung injury. The ongoing escalation of bacterial resistance to antibiotics has rendered traditional prevention and control measures insufficient to keep pace with the evolution of bacterial resistance genes, urgently requiring the scientific community to accelerate the development of novel antimicrobial strategies to address the public health threat posed by multidrug-resistant strains. A substantial body of research has demonstrated that miRNAs are involved in the regulation of infection and inflammation associated with ALI and ARDS. This study investigated the mechanism by which endogenous miRNA, miR-423-5p, regulated LPS/GPS-induced inflammation and examined the mechanism by which exogenous miRNA derived from Scutellaria baicalensis regulated LPS-induced inflammation. Bioinformatics prediction and experimental verification showed that miR-423-5p expression was reduced in RAW264.7 cells and mouse lung tissue after LPS/GPS infection, while IKBKE expression increased. Functionally, miR-423-5p acted as a regulator, overexpression worsening and inhibition alleviating LPS/GPS-induced inflammation. Mechanistically, miR-423-5p negatively regulated the IKBKE/IRF3/IFN-β axis, thereby inhibiting the production of downstream inflammatory factors. Simultaneously, bioinformatics predictions and experimental validation demonstrated that miRNAs derived from Scutellaria baicalensis (HQ1, HQ2, HQ3) can cross-regulate the LPS-induced IKBKE/IRF3/IFN-β pathway, thereby suppressing inflammatory responses. This study firstly proposes that Scutellaria baicalensis-derived miRNAs exert anti-inflammatory and antibacterial effects through cross-regulatory mechanisms of mammalian genes, providing therapeutic directions for bacterial pneumonia while offering a potential avenue for natural drug development.