Mechanism of Schisandrae Chinensis Fructus on Treating Missed Abortion Based on Network Pharmacology and Preliminary Verification

LIANG Jing; QIAO Lin-jing; HOU Hai-yan

doi:10.12280/gjfckx.20230445

Abstract：Objective:To explore the potential mechanism of Schisandrae chinensis fructus on the treatment of missed abortion based on a network pharmacology approach and verified experimentally.Methods:The system pharmacology approach was used to find and screen the active components and targets of Schisandrae chinensis from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, the genes related to missed abortion,and identify the targets of Schisandra chinensis for prevention and treatment of missed abortion.The"drug component-target"network was constructed by using Cytoscape to screen key compounds.The protein-protein interaction(PPI)network was established by String,and the core targets were screened by the Cytoscape-CytoNCA topology analysis.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed on the target genes to predict their possible signal pathways and explore their molecular mechanisms.Finally,the mechanism was validated with the help of human chorionic villous trophoblast cell line(HTR-8/SVneo)using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)detection and Western blotting assays.Results:Seven active compounds of Schisandra chinensis were identified from TCMSP database.Schisandrae chinensis has five potential targets for the prevention and treatment of missed abortion.The PPI network shows that androgen receptor(AR),estrogen receptor(ER),cyclooxygenase-2(COX-2),nuclear receptor coactivator 2(NCOA2)and acetylcholine esterase(ACHE)may be the core targets of Schisandrae chinensis for the prevention and treatment of missed abortion.Forty-four cell biological processes were obtained by GO enrichment analysis,and two related signal pathways were obtained by KEGG pathway enrichment analysis,mainly including thyroid hormone signal pathway and estrogen signal pathway.During the process of validating the mechanism using a cell model,it was found that the protein and/or mRNA levels of AR,ER,and COX-2 in cells treated with benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide(BPDE)were higher than those of normal cells,while the protein and/or mRNA levels of AR,ER,and COX-2 were reduced in cells pretreated with Schisandrin B(Sch B)first and then tainted with BPDE compared with those not pretreated with Sch B.The NCOA2 and ACHE protein and/or mRNA levels did not change significantly.Conclusions:Schisandrae chinensis may exert its preventive and therapeutic effects on missed abortion through anti-inflammatory and hormonal receptor regulation,and this protective effect may be achieved through the estrogen signaling pathway.