Effect and protective mechanism of huperzine A on alveolar epithelial cells in acute lung injury based on network pharmacology and in vitro experimentation
Based on network pharmacology and experimental validation,this study investigated the protective effect and mech-anism of huperzine A(Hup A)on alveolar epithelial cells in acute lung injury(ALI).Firstly,the potential targets for Hup A to protect against ALI were identified by searching the public database for related targets of Hup A and ALI,and obtaining their intersection.Subsequently,the core target of Hup A protection against ALI was screened through construction of protein interaction network and"component-target-pathway"network,followed by verification through molecular docking.Further-more,a cell model was established by stimulating mouse alveolar epithelial cells(MLE-12)with lipopolysaccharide(LPS)and pre-treating them with Hup A.The protective effect of Hup A was verified by detecting changes in cell viability,interleu-kin-6(IL-6)level,super oxide dismutase(SOD)level and malondialdehyde(MDA)level.Finally,Western blot test was conducted to verify alterations in protein levels of key targets.Network pharmacological analysis revealed 144 potential thera-peutic targets for Hup A,implicating its involvement in the regulation of biological processes such as protein kinase activity,oxidative stress,inflammatory response,and signaling pathways including phosphatidyl-inositol 3-kinase-serine-threonine ki-nase(PI3K-Akt)and mitogen-activated protein kinase(MAPK).Molecular docking results demonstrated favorable binding activity of Hup A with Akt1,Akt2 and Mapk1(also known as extracellular regulated protein kinases,Erk).Cell experiments indicated that Hup A effectively ameliorated LPS-induced decline in cell viability(P＜0.05),reduced levels of IL-6,MDA and p-Erk1/2/Erk1/2(P＜0.05),while increasing SOD and p-Akt1/Akt1 levels(P＜0.05).In conclusion,Hup A may exert a protective effect in LPS induced ALI through the regulation of Akt1 and Mapk1 targets within alveolar epithelial cells.
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