Exploring the Mechanism of SSD Compound on Acute Lung Injury Improvement Based on Network Pharmacology and Experiment Research
In this study,the active ingredients and potential targets of each Traditional Chinese Medicine(TCM)in SSD compound were obtained from the TCMSP database and Swiss Target Prediction online prediction platform,while GeneCards,DisGeNET,and GEO databases were used to obtain the acute lung injury related(ALI)targets.The TCM-active ingredient-target-disease network and PPI network were constructed by using Cytoscape 3.9.1 software and the STRING database,and the core ingredients and targets were subsequently screened.GO and KEGG analysis of core targets were performed by the David database.Molecular docking of core ingredients and core targets was performed using AutoDock Vina 1.2.3 software,and the result was visualized by PyMOL 2.6.0.Finally,the lipopolysaccharide(LPS)induced ALI rat model was established to verify the effect of SSD on ALI.The results showed that 30 active ingredients of SSD were screened,and 9 ALI improvement related targets were identified,among which the main core ingredients were β-sitosterol,mandenol,kaempferol,and 26-O-β-D-glucopyranosyl-3β,26-dihydroxy-5-cholesten-16,22-dioxo-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside_qt,the main core targets were interleukin-6(IL-6),tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),Jun proto-oncogene(JUN),and serpin E1(SERPINE1).GO and KEGG analysis showed that SSD improved ALI through multiple biological processes,such as positive regulation of interleukin-8 production,leukocyte adhesion to vascular endothelial cell,cellular response to lipopolysaccharide,vascular endothelial growth factor production,protease binding,interleukin-6 receptor binding,transcription regulatory region sequence-specific DNA binding,regulation of AGE-RAGE signaling pathway and TNF signaling pathway in diabetic complications and other ways,these can play a synergistic role in improving ALI.Molecular docking results showed that all 3 core components were well combined with the 5 core targets.The results of animal experiments showed that medium and high dose of SSD could significantly reduce the levels of inflammatory factors TNF-α,IL-1β and IL-10 in bronchoalveolar lavage fluid and lung tissue of ALI rats,further pathological observation also showed that SSD could alleviate lung tissue injury.This study initially reveals that SSD improves ALI by the combined action of multiple components,multiple targets,and multiple pathways,which provides a theoretical basis for the application of SSD in lung health care and the prevention of ALI.