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

doi:10.12280/gjfckx.20230445

Abstract

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, https://old.tcmsp-e.com/tcmsp.php), find 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.

Key words: Schisandrae chinensis fructus, Abortion, missed, Mechanism, Network pharmacology

LIANG Jing, QIAO Lin-jing, HOU Hai-yan. Mechanism of Schisandrae Chinensis Fructus on Treating Missed Abortion Based on Network Pharmacology and Preliminary Verification[J]. Journal of International Obstetrics and Gynecology, 2024, 51(2): 167-175.

Figures/Tables 8

References 35

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基因名称	上游引物（5′~3′）	下游引物（5′~3′）	片段长度（bp）
COX-2	AGAGCAGAGAGATGAAATACC	AGGAGAACAGATGGGATTAC	266
AR	CTACATCAAGGAACTCGATCGT	CATGTGTGACTTGATTAGCAGG	159
ER	TACTGCATCAGATCCAAGGGAA	CCTCGGGGTAGTTGTACAC	128
NCOA2	GCTGCACAAACGAAGAGCAA	CATGTCCTGACCTGGGTTCC	210
ACHE	AGCGACTGATGCGATACTGG	CCATGGGTGAAGCCTGGG	250
GAPDH	CAGGAGGCATTGCTGATGAT	GAAGGCTGGGGCTCATTT	137

基因名称	上游引物（5′~3′）	下游引物（5′~3′）	片段长度（bp）
COX-2	AGAGCAGAGAGATGAAATACC	AGGAGAACAGATGGGATTAC	266
AR	CTACATCAAGGAACTCGATCGT	CATGTGTGACTTGATTAGCAGG	159
ER	TACTGCATCAGATCCAAGGGAA	CCTCGGGGTAGTTGTACAC	128
NCOA2	GCTGCACAAACGAAGAGCAA	CATGTCCTGACCTGGGTTCC	210
ACHE	AGCGACTGATGCGATACTGG	CCATGGGTGAAGCCTGGG	250
GAPDH	CAGGAGGCATTGCTGATGAT	GAAGGCTGGGGCTCATTT	137

成分代码	化合物名称	口服生物利用度（%）	药物相似性	靶点	靶点通用名
MOL004624	Longikaurin A	47.72	0.53	Muscarinic acetylcholine receptor M1	CHRM1
				Muscarinic acetylcholine receptor M2	CHRM2
				Trypsin-1	PRSS1
MOL005317	Deoxyharringtonine	39.27	0.81	Androgen receptor	AR
				Mineralocorticoid receptor	NR3C2
MOL008956	Angeloylgomisin O	31.97	0.85	Androgen receptor	AR
MOL008957	Schizandrer B	30.71	0.83	Prostaglandin G/H synthase 2	PTGS2*
MOL008968	Gomisin A	30.69	0.78	Acetylcholinesterase	ACHE
MOL008978	Gomisin R	34.84	0.86	Estrogen receptor 1	ESR1**
				Androgen receptor	AR
				Prostaglandin G/H synthase 2	PTGS2*
				Trypsin-1	PRSS1
				Nuclear receptor coactivator 2	NCOA2
MOL008992	Wuweizisu C	46.27	0.84	Acetylcholinesterase	ACHE
				Gamma-aminobutyric acid receptor subunit alpha-1	GABRA1

成分代码	化合物名称	口服生物利用度（%）	药物相似性	靶点	靶点通用名
MOL004624	Longikaurin A	47.72	0.53	Muscarinic acetylcholine receptor M1	CHRM1
				Muscarinic acetylcholine receptor M2	CHRM2
				Trypsin-1	PRSS1
MOL005317	Deoxyharringtonine	39.27	0.81	Androgen receptor	AR
				Mineralocorticoid receptor	NR3C2
MOL008956	Angeloylgomisin O	31.97	0.85	Androgen receptor	AR
MOL008957	Schizandrer B	30.71	0.83	Prostaglandin G/H synthase 2	PTGS2*
MOL008968	Gomisin A	30.69	0.78	Acetylcholinesterase	ACHE
MOL008978	Gomisin R	34.84	0.86	Estrogen receptor 1	ESR1**
				Androgen receptor	AR
				Prostaglandin G/H synthase 2	PTGS2*
				Trypsin-1	PRSS1
				Nuclear receptor coactivator 2	NCOA2
MOL008992	Wuweizisu C	46.27	0.84	Acetylcholinesterase	ACHE
				Gamma-aminobutyric acid receptor subunit alpha-1	GABRA1