YuPingFengSan ameliorates LPS-induced acute lung injury and gut barrier dysfunction in mice

Ethnopharmacological relevance: Yupingfengsan (YPFS) is a traditional Chinese medicine decoction. YPFS com-prises Astragalus mongholicus Bunge (Huangqi), Atractylodes rubra Dekker (Baizhu), and Saposhnikovia divaricata (Turcz.ex Ledeb.) Schischk (Fangfeng). YPFS is commonly used to treat chronic obstructive pulmonary disease, asthma, respiratory infections, and pneumonia, but the mechanism of action remains unclear. Aim of the study: Acute lung injury (ALI) and its severe form of acute respiratory distress syndrome (ARDS) cause morbidity and mortality in critical patients. YPFS is a commonly used herbal soup to treat respiratory and im-mune system diseases. Nevertheless, the effect of YPFS on ALI remains unclear. This study aimed to investigate the effect of YPFS on lipopolysaccharide (LPS)-induced ALI in mice and elucidate its potential molecular mechanisms. Materials and methods: The major components of YPFS were detected by High-performance liquid chromatog-raphy (HPLC). C57BL/6J mice were given YPFS for seven days and then treated with LPS. IL-1 beta, IL-6, TNF-alpha, IL-8, iNOS, NLRP3, PPAR gamma, HO-1, ZO-1, Occludin, Claudin-1, AQP3, AQP4, AQP5, ENaC alpha, ENaC beta, EnaC gamma mRNA in lung and ZO-1, Occludin, Claudin-1, AQP3, AQP4, AQP5, ENaC alpha, ENaC beta, and EnaC gamma mRNA in colon tissues were measured by Real-Time Quantitative PCR (RT-qPCR). The expressions of TLR4, MyD88, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), ASC, MAPK signaling pathway, Nrf2, and HO-1 in the lung were detected by Western blot. Plasma inflammatory factors Interleukin (IL)-1 beta, IL-6, and Tumor Necrosis Factor-alpha (TNF-alpha) were determined by Enzyme-linked Immunosorbent Assay (ELISA). Lung tissues were processed for H & E staining, and colon tissues for HE, WGA-FITC, and Alcian Blue staining. Results: The results showed that YPFS administration alleviated lung injury and suppressed the production of inflammatory factors, including IL-1 beta, IL-6, and TNF-alpha. Additionally, YPFS reduced pulmonary edema by pro-moting the expressions of aquaporin and sodium channel-related genes (AQP3, AQP4, AQP5, ENaC alpha, ENaC beta, and EnaC gamma). Further, YPFS intervention exhibited a therapeutic effect on ALI by inhibiting the activation of the NLRP3 inflammasome and MAPK signaling pathways. Finally, YPFS improved gut barrier integrity and sup-pressed intestinal inflammation in LPS-challenged mice. Conclusions: YPFS protected mice against LPS-induced ALI by attenuating lung and intestinal tissue damage. This study sheds light on the potential application of YPFS to treat ALI/ARDS.