Active Components and Potential Molecular Mechanisms of Panax Notoginseng in Alleviating Intestinal...

Intestinal ischemia/reperfusion (I/R)-induced acute lung injury (ALI) is a key contributing factor to mortality and disability following surgery for acute abdominal emergencies. Panax notoginseng (PN) exerts a significant alleviating effect on intestinal I/R-induced ALI. The objective of this study is to use Ultra-high performance liquid chromatography-Mass spectrometry (UHPLC-MS/MS), network pharmacology, and molecular docking methods to investigate the main active components of PN in alleviating intestinal I/R-induced ALI and their molecular mechanisms.

The chemical compositions of PN were identified using UHPLC-MS/MS, and potential targets for these compounds were predicted using the Swiss Target Prediction database. Subsequently, Cytoscape 3.7.2 was utilized to design a network that demonstrates the interactions of drugs, components, and targets. Targets associated with intestinal I/R-induced ALI were detected using the GeneCards and OMIM databases. Cross-- targets between the drug and the disease were analyzed, and a PPI network was established via the STRING database. The targets that overlap were subjected to GO and KEGG enrichment analyses. The interactions between core bioactive substances and key proteins were validated through molecular docking.

UHPLC-MS/MS analysis identified 71 major chemical constituents in PN. Protein- protein interactions (PPI) network analysis revealed that TNF, IL-6, AKT1, and IL-1β were the most highly interconnected hub targets. The GO analysis revealed a notable enrichment in biological processes such as response to xenobiotic stimulus, positive regulation of gene expression, and inflammatory response. According to the KEGG pathway analysis, significant signaling pathways include PI3K-Akt, TNF, and HIF-1. The stable binding conformations of L-Tryptophan, Quercetin, Adenosine, Linolenic acid ethyl ester, and Bryodulcosigenin with core targets TNF, IL-6, AKT1, IL-1β, and GAPDH were confirmed through molecular docking.

This computational study provides a systematic framework for deciphering the complex mechanisms of traditional medicines. Our analysis proposes that PN alleviates intestinal I/R-induced ALI through a "multi-component, multi-target, multi-pathway" mechanism. The findings serve as a robust hypothesis-generating resource, offering precise candidates and pathways for future experimental validation.

This research predicts the effective components of PN and their potential molecular mechanisms in treating intestinal I/R-induced ALI, laying a theoretical groundwork for future experimental confirmation and clinical application.