Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 15, 2024

Introduction Due to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoni ae (KP)-induced pneumonia. Research has shown that single herbs SiHuangQingXinWan (SHQXW) are effective treating pneumonia caused by KP. The PI3K/AKT signaling pathway garnered attention its potential role management bacterial infections. This study aimed evaluate anti-pneumonia effect SHQXW investigate mechanism action. Materials Methods plant metabolites molecular targets context were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) bioinformatics analysis. therapeutic was evaluated KP-induced murine model with imipenem/cilastatin as positive control. Transcriptomics non-targeted metabolomics carried out unveil mechanisms effects. Additionally, an in-depth exploration on conducted this study. Results A total 24 285 SHQXW-pneumonia-related selected Homo sapiens identified tested doses significantly reduced mortality, improved body weight, decreased lung index, load, alleviated pathological damage ( p < 0.05). Notably, 1.3 g/kg/day provided most protective outcome. Furthermore, demonstrated ability suppress production inflammatory factors such IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, TNF-α. Analysis transcriptomic metabolomic data revealed could modulate inflammation-related pathways (TNF, HIF-1, NF-κB, PI3K/AKT) regulate pulmonary inflammation. Additional experiments using RT-qPCR western blotting indicated may exert anti-inflammatory effects activating pathway. Discussion findings indicate effectively reduces inflammation mice modulating metabolites, rather than directly inhibiting growth introduces novel treatment approach presents outlook drug development.

Language: Английский