Zhenqi Granules Attenuates the Inflammatory Response of Pulmonary Epithelial Cells by Inhibiting Endoplasmic Reticulum Stress in MRSA Infection

The severe inflammatory response of pulmonary epithelial cells is the main pathological feature of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Zhenqi granules (ZQ), a compound herbal formula composed of Astragalus membranaceus and Ligustrum lucidum, has potential therapeutic effects on this inflammatory response, but its mechanism of action is still unclear. The study aims to explore the effect and mechanism of ZQ on the inflammatory response induced by establishing an in vitro model of MRSA-infected human pulmonary bronchial epithelial cells (MRSA-BEAS-2B). ZQ (10 mg/mL) had no inhibitory effect on MRSA or its biofilm, but it reduced the levels of LDH and c-di-AMP in MRSA-BEAS-2B cells. The mechanism is attributed to the downregulation of endoplasmic reticulum-related protein pathways, specifically involving a decrease in endoplasmic reticulum stress-related proteins such as STING and ERAdP; a decrease in inflammation pathway-related factors such as NF-ĸB, IFR3, NLRP3, and TLR4; and an increase in the STING antagonist RECON. These effects resulted in a reduction in the proinflammatory cytokines IFN-β, IL-1β, IL-6, and IL-18, thereby inhibiting pulmonary inflammation. ZQ attenuates the inflammatory response of pulmonary epithelial cells by inhibiting c-di-AMP-related endoplasmic reticulum stress during MRSA infection. This study provides a basis for the clinical application of ZQ and improves the development of treatment strategies for pulmonary MRSA infection.