Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury

Abstract

Context Keguan-1 (KG-1) plays a vital role in enhancing the curative effects, improving quality of life, and reducing the development of acute lung injury (ALI).Objective To unravel the protective effect and underlying mechanism of KG-1 against ALI.Materials and methods C57BL/6J mice were intratracheally instilled with lipopolysaccharide to establish the ALI model. Then, mice in the KG-1 group received a dose of 5.04 g/kg for 12 h. The levels of proinflammatory cytokines, chemokines, and pathological characteristics were determined to explore the effects of KG-1. Next, untargeted metabolomics was used to identify the differential metabolites and involved pathways for KG-1 anti-ALI. Network pharmacology was carried out to predict the putative active components and drug targets of KG-1 anti-ALI.Results KG-1 significantly improved the levels of TNF-α (from 2295.92 ± 529.87 pg/mL to 1167.64 ± 318.91 pg/mL), IL-6 (from 4688.80 ± 481.68 pg/mL to 3604.43 ± 382.00 pg/mL), CXCL1 (from 4361.76 ± 505.73 pg/mL to 2981.04 ± 526.18 pg/mL), CXCL2 (from 5034.09 ± 809.28 pg/mL to 2980.30 ± 747.63 pg/mL), and impaired lung histological damage. Untargeted metabolomics revealed that KG-1 significantly regulated 12 different metabolites, which mainly related to lipid, amino acid, and vitamin metabolism. Network pharmacology showed that KG-1 exhibited anti-ALI effects through 17 potentially active components acting on seven putative drug targets to regulate four metabolites.Discussion and conclusions This work elucidated the therapeutic effect and underlying mechanism by which KG-1 protects against ALI from the view of the metabolome, thus providing a scientific basis for the usage of KG-1.

Keywords

• Untargeted metabolomics
• metabolites
• interaction network
• modulatory effects