Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
IntroductionDue to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.Materials and MethodsThe potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.ResultsA total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DiscussionThe findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.
IntroductionDue to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.Materials and MethodsThe potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.ResultsA total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DiscussionThe findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.