Pharmacological effects and mechanism of Maxing Shigan decoction in the treatment of Pseudomonas aeruginosa pneumonia

Abstract

Ethnopharmacological relevance: Maxing Shigan Decoction (MXSG) is a traditional Chinese Medicine effectively used in respiratory infections and bacterial pneumonia. However, the mechanism of MXSG treating acute Pseudomonas aeruginosa (P. aeruginosa) pneumonia is still unclear.

Aim of the study: This study aimed to investigate the therapeutic effects of MXSG on acute P. aeruginosa pneumonia and explore its potential mechanisms.

Materials and methods: HPLC-MS analysis was performed to analyze the chemical composition. Antibacterial effects in vitro were evaluated by minimum inhibitory concentration (MIC). Forty-five male BALB/c mice were divided into control group, model group, levofloxacin group, MXSG-L (7.7 g/kg/d), and MXSG-H group (15.4 g/kg/d). Mice were intranasal instillation with P. aeruginosa to induce acute P. aeruginosa pneumonia model. Levofloxacin and MXSG were administered by oral gavage once a day. After 3 days of treatment, the lung index measurement, micro-CT, arterial blood gas analysis, bacteria load determination, and HE staining were performed. Network pharmacological analysis and transcriptome sequencing were employed to predict the potential mechanisms of MXSG on bacterial pneumonia. The expressions of relating genes were detected by immunofluorescence, Western blot, and RT-PCR.

Results: In vitro, MIC of P. aeruginosa is greater than 500 mg/mL. In the treatment of acute P. aeruginosa pneumonia model, MXSG significantly improved body weight loss, lung index, and pulmonary lesions. MXSG treatment also reduced the bacterial load and ameliorated oxygen saturation significantly. Transcriptomes, immunofluorescence, Western blot, and RT-PCR analysis showed MXSG treating acute P. aeruginosa pneumonia through the IL-17 signaling pathway and HIF-1α/IL-6/STAT3 signaling pathway.

Conclusions: We demonstrated the efficacy and mechanism of MXSG in the treatment of acute P. aeruginosa pneumonia, which provides a scientific basis for its clinical application.

Keywords: Acute bacterial pneumonia; Cytokine storm; HIF signaling pathway; IL-17 signaling pathway; Maxing Shigan decoction; P. aeruginosa; Traditional Chinese medicine.