首页|Metabolomics combined with network pharmacology reveals anti-asthmatic effects of Nepeta bracteata on allergic asthma rats
Metabolomics combined with network pharmacology reveals anti-asthmatic effects of Nepeta bracteata on allergic asthma rats
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Metabolomics combined with network pharmacology reveals anti-asthmatic effects of Nepeta bracteata on allergic asthma rats
Objective:To investigate the mechanisms that underlie the anti-asthmatic effects of Nepeta bracteata(DBJJ,Dabao Jingjie in Chinese)in rats by integrating metabolomics and network pharmacology.Methods:In this study,the rat model of asthma was induced by ovalbumin(OVA),and the rats were trea-ted with a decoction of N.bracteata.Pathological changes in lung tissue were observed,and the quantifi-cation of eosinophils(EOS)and white blood cells(WBC)in bronchoalveolar lavage fluid was performed.Furthermore,the serum levels of asthma-related factors induced by OVA were assessed.1H NMR spec-troscopy serum metabolomics method was utilized to identify differential metabolites and their associ-ated metabolic pathways.UPLC-QE-MS/MS combined with network pharmacology was employed to predict the core targets and pathways of DBJJ in its action against asthma.The anti-asthmatic properties of DBJJ were investigated using an integrated approach of metabolomics and network pharmacology.The findings were validated through molecular docking and Western blotting analysis of the key targets.Results:The administration of DBJJ effectively alleviated OVA-induced lung histopathological changes and decreased the number of EOS and WBC in BALF.Additionally,DBJJ inhibited the OVA-induced eleva-tion of TNF-α,IL-18,Ig-E,EOS,IL-1 β,MDA,VEGF-A,and TGF-β1.A total of 21 biomarkers and 10 pathways were found by metabolomics analysis.A total of 29 compounds were identified by UPLC-QE-MS/MS,in which 13 active components were screened by oral availability and Caco-2 cell permeability,the 120 tar-gets and 173 KEGG pathways were predicted.The integration of metabolomics and network pharmaco-logical analysis revealed that DBJJ's main constituents,including ferulic acid and ursolic acid,exerted their effects on four targets,namely DAO and NOS2,as well as their associated metabolites and pathways.The active constituents of DBJJ demonstrated a high binding affinity towards DAO and NOS2.Furthermore,DBJJ was observed to decrease the protein expression and phosphorylation levels of NOS2,MAPK,and STAT3.Conclusion:The administration of DBJJ demonstrates notable anti-asthma properties in rats with allergic asthma.This effect can be attributed to the modulation of various targets,including NOS2,MAPK,and STAT3,by primary constituents such as ferulic acid and ursolic acid.
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NSTL
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