To explore effect and mechanism of Shengjiang Powder in treatment of acute lung injury based on network pharmacology and experimental verification
Objective To explore the mechanism of Shengjiang Powde in the treatment of acute lung injury(ALI)based on network pharmacology and animal experiments.Methods The components and targets of Shengjiang Powder were searched in Traditional Chinese Medicine Systems Pharmacology Analysis Platform Database(TCMSP)and Swiss Target Prediction Database,and the disease targets of ALI were searched in Gene Cards Database.The drug-disease intersection targets were uploaded to the STRING data platform for protein interaction analysis.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were performed using the DAVID website.In order to further explore the effect of Shengjiang Powder on ALI,a mouse ALI model was established to observe the pathological damage of lung tissue.In addition to the control group,each administration group of Shengjiang Powder was ig administered with 20 mL·kg-1 drug solution(the doses of powder,water decoction and its high and low dose groups were 175 and 350 mg·kg-1,respectively,once a day in the morning and evening,fora total of 14 days).On the 12 th day,dexamethasone(5 mg kg-1)was injected intraperitoneally for three days.On the 15th day,1 mg·mL-1 lipopolysaccharide(5 mg·kg-1)was instilled into the trachea for modeling.The levels of interleukin 6(IL-6),interleukin 1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.The mRNA expressions of Toll-like receptor 4(TLR4),phosphorylated-mitogen-activated protein kinase p38(p38-MAPK),extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK-1)were detected by RT-PCR.Protein expressions of nuclear factor kappa B(NF-κB)and human nuclear factorκB inhibitory protein α(IκBα)were detected by Western blotting.Results It was predicted that there were 32 active components,292 key targets,1 454 ALI disease targets and 95 intersection targets of Shengjiang Powder and ALI.The key targets of Shengjiang Powder in the treatment of ALI were mainly involved in NF-κB,MAPK and other signaling pathways.The results of ALI mouse model showed that Shengjiang Powder could significantly reduce the inflammation of lung tissue in ALI mice and improve the thickening of alveolar septum and alveolar wall.Shengjiang Powder could reduce the content of inflammatory factors IL-6,IL-1βand TNF-α in serum.The expression of TLR4,p38-MAPK,ERK and JNK-1 mRNA was down-regulated.Western blotting results showed that Shengjiang Powder could activate IκBα protein and alleviate ALI by inhibiting the phosphorylation level of NF-κB protein.Conclusion Shengjiang Powder can synergistically treat ALI based on the characteristics of multi-component,multi-target and multi-pathway.The mechanism may be related to NF-κB,MAPK and other signaling pathways,and the effect of Shengjiang Powder on ALI is better than that of water extract.
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