Mechanism of Shizi Sanhua Decoction on Male Oligospermia Revealed by Herbs-Ingredients and Disease Co-Target Genes Sub-Network

Page: [937 - 945] Pages: 9

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Abstract

Background: Shizi Sanhua Decoction, a traditional Chinese medicine (TCM) prescription, shows a treatment advantage on male oligospermia. While due to the complexity of the compatibility (multiple herbs composition), the underlying mechanism remains to be deciphered.

Methods: Herbs-ingredients-target genes were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SWISSADME database, intersecting with oligospermia-related derived from DisGeNET to obtain co-target genes. The protein-protein interaction (PPI) network of co-target genes was constructed based on the STRING database, and highly condensed sub-networks and top 10 Hub genes were identified with the CytoHubba plug-in. Herbs, ingredients and KEGG enrichment information were projected onto the identified highly condensed subnetwork to build Herbs-ingredients and disease co-target genes sub-network.

Results: After integration of herbs-ingredients-target genes (n=453) with disease genes (n=329), 29 cotarget genes were obtained. Among them, PARP1, AR, CYP17A1, ESR1, ABCB1, STS, CFTR, SOAT1, NR5A1, and HIF1A were related to male infertility (WP4673-WikiPathways). Sub-network analysis further revealed the top 10 Hub genes, and the relation with the herbs and ingredients was demonstrated in the sub-network of herbs-ingredients and disease co-target genes. As expected, reproductive- related biological processes (mammary gland epithelium development, GO:0061180; Oocyte meiosis, hsa04114; Progesterone-mediated oocyte maturation, hsa04914) were enriched. Thyroid hormone signaling pathway (hsa04919), Serotonergic synapse (hsa04726), Chemical carcinogenesisreactive oxygen species (hsa05208), and Endocrine resistance (hsa01522) may contribute to the development of male oligospermia.

Conclusion: Constructed herbs-ingredients and disease co-target genes sub-network discloses specific bioprocesses and molecular targets of Shizi Sanhua Decoction in oligospermia treatment.

Keywords: Shizi Sanhua Decoction, oligospermia, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform

[1]
Choy JT, Amory JK. Nonsurgical management of oligozoospermia. J Clin Endocrinol Metab 2020; 105(12): e4194-207.
[http://dx.doi.org/10.1210/clinem/dgaa390] [PMID: 32583849]
[2]
McLachlan RI. Approach to the patient with oligozoospermia. J Clin Endocrinol Metab 2013; 98(3): 873-80.
[http://dx.doi.org/10.1210/jc.2012-3650] [PMID: 23472228]
[3]
Turgut H. The effect of varicocelectomy on the pregnancy rate in patients with severe oligospermia. Niger J Clin Pract 2020; 23(12): 1744-7.
[http://dx.doi.org/10.4103/njcp.njcp_173_20] [PMID: 33355829]
[4]
Ribeiro LM, Sasaki LMP, Silva AA, et al. Overweight, obesity and assisted reproduction: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2022; 271: 117-27.
[http://dx.doi.org/10.1016/j.ejogrb.2022.01.019] [PMID: 35183001]
[5]
Wu P, Sharma GV, Mehta LS, et al. In hospital complications in pregnancies conceived by assisted reproductive technology. J Am Heart Assoc 2022; 11(5): e022658.
[http://dx.doi.org/10.1161/JAHA.121.022658] [PMID: 35191320]
[6]
Qin J, Wang H, Sheng X, Liang D, Tan H, Xia J. Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: A meta-analysis of cohort studies. Fertil Steril 2015; 103(6): 1492-508.
[http://dx.doi.org/10.1016/j.fertnstert.2015.03.018]
[7]
Ru J, Li P, Wang J, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6(1): 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[8]
Zhao X, Wang Y, Cui Q, et al. A parallel phenotypic versus target-based screening strategy for RNA-dependent RNA polymerase inhibitors of the Influenza A virus. Viruses 2019; 11(9): 826.
[http://dx.doi.org/10.3390/v11090826] [PMID: 31491939]
[9]
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7(1): 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[10]
Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res 2014; 42(Web Server issue): W32-8.
[http://dx.doi.org/10.1093/nar/gku293]
[11]
Bateman A, Martin M-J, Orchard S, et al. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49(D1): D480-9.
[http://dx.doi.org/10.1093/nar/gkaa1100] [PMID: 33237286]
[12]
Piñero J, Ramírez-Anguita JM, Saüch-Pitarch J, et al. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res 2020; 48(D1): D845-55.
[PMID: 31680165]
[13]
Micallef L, Rodgers P. eulerAPE: Drawing area-proportional 3-Venn diagrams using ellipses. PLoS One 2014; 9(7): e101717.
[http://dx.doi.org/10.1371/journal.pone.0101717] [PMID: 25032825]
[14]
Liu T, Chen W, Chen X, et al. Network pharmacology identifies the mechanisms of action of TaohongSiwu decoction against essential hypertension. Med Sci Monit 2020; 26: e920682.
[http://dx.doi.org/10.12659/MSM.920682] [PMID: 32187175]
[15]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498-504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[16]
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014; 8 (Suppl. 4): S11.
[17]
Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10(1): 1523.
[http://dx.doi.org/10.1038/s41467-019-09234-6] [PMID: 30944313]
[18]
Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28(1): 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]
[19]
The Gene Ontology Consortium. The gene ontology resource: 20 years and still going strong. Nucleic Acids Res 2019; 47(D1): D330-8.
[http://dx.doi.org/10.1093/nar/gky1055] [PMID: 30395331]
[20]
Yu G, Wang LG, Han Y, He QY. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[21]
Yang K, Li SG, Zhang TY, Dong PP, Zeng QQ. Runjing extract promotes spermatogenesis in rats with ornidazole-induced oligoasthenoteratozoospermia through extracellular signal-regulated kinase signalling, and regulating vimentin expression. J Tradit Chin Med 2021; 41(4): 581-7.
[PMID: 34392651]
[22]
Bai X, Tang Y, Li Q, et al. Network pharmacology integrated molecular docking reveals the bioactive components and potential targets of Morinda officinalis–Lycium barbarum coupled-herbs against oligoasthenozoospermia. Sci Rep 2021; 11(1): 2220.
[http://dx.doi.org/10.1038/s41598-020-80780-6] [PMID: 33500463]
[23]
Cheng P, Chen H, Zhang RP, Liu S, Zhou-Cun A. Polymorphism in DNMT1 may modify the susceptibility to oligospermia. Reprod Biomed Online 2014; 28(5): 644-9.
[http://dx.doi.org/10.1016/j.rbmo.2014.01.003] [PMID: 24631383]
[24]
Singh P, Schimenti JC. The genetics of human infertility by functional interrogation of SNPs in mice. Proc Natl Acad Sci USA 2015; 112(33): 10431-6.
[http://dx.doi.org/10.1073/pnas.1506974112] [PMID: 26240362]
[25]
Amadi K, Sabo MA, Sagay AS. Thyroid hormone: The modulator of erectile function in the rabbit. Niger J Physiol Sci 2006; 21(1-2): 83-9.
[PMID: 17242734]
[26]
Agarwal A, Mulgund A, Sharma R, Sabanegh E. Mechanisms of oligozoospermia: An oxidative stress perspective. Syst Biol Reprod Med 2014; 60(4): 206-16.
[http://dx.doi.org/10.3109/19396368.2014.918675] [PMID: 24815996]
[27]
Zhang K, Fu L, An Q, et al. Effects of Qilin pills on spermatogenesis, reproductive hormones, oxidative stress, and the TSSK2 gene in a rat model of oligoasthenospermia. BMC Compl Med Ther 2020; 20(1): 42.
[http://dx.doi.org/10.1186/s12906-019-2799-7] [PMID: 32046715]
[28]
Aiman J, Griffin J. The frequency of androgen receptor deficiency in infertile men. J Clin Endocrinol Metab 1982; 54(4): 725-32.
[http://dx.doi.org/10.1210/jcem-54-4-725] [PMID: 6801070]