Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

Abstract

Background Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. Methods Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. Results DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. Conclusion This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI. Graphical Abstract

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway

“…T-tests were performed to determine if there were significant differences in the relative peak areas of biomarkers between groups, selecting metabolites with statistical significance ( P < 0.05). The Human Metabolome Database (HMDB, http://www.hmdb.ca/ ) was utilized to identify potential markers [ 22 ]. Finally, differential metabolites were analysed for metabolic pathway enrichment using MetaboAnalyst 5.0 ( http://www.metaboanalyst.ca/ ) [ 23 ].…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Besides, several studies have shown that the activation of the PI3K/AKT pathway increases inflammatory cytokines by activating the downstream NF-κB signal [109][110][111]. However, some recent studies have drawn a different conclusion, suggesting that the activation of PI3K/AKT is related with the alleviation of lung inflammation [112,113]. Zhong et al [113] reported that PI3K/AKT activation inhibited downstream NF-κB and NLRP3 inflammasome to alleviate inflammation in LPS-induced ALI model.…”