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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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General Research Article

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Zuogui Yin in the Treatment of Male Infertility

Author(s): Qi Zhao, Hengheng Dai, Jisheng Wang, Fei Yan, Guejin Jang, Jianxiong Ma, Bin Wang* and Haisong Li*

Volume 24, Issue 6, 2021

Published on: 24 August, 2020

Page: [803 - 813] Pages: 11

DOI: 10.2174/1386207323999200824112611

Price: $65

Abstract

Background and Aim: Traditional Chinese medicine (TCM), as a complementary and alternative therapy, has played increasingly important roles in clinical treatment and disease prevention. Zuogui Yin (ZGY) is one of the well-known TCM prescriptions used for the treatment of male infertility. To fully reveal the potential mechanisms underlying the therapeutic effects of ZGY on male infertility, a network pharmacology approach was conducted at the molecular level.

Methods: Network pharmacology approach was used in this study, which mainly included active compound screening, target prediction, gene enrichment analysis, and network analysis.

Results: The network analysis successfully identified 148 potential active ingredients of ZGY and 155 predicted targets that were associated with male infertility. ZGY might play a role in the treatment of male infertility by regulating ten hub targets (VEGFA, CASP3, TNF, AKT1, EGF, EGFR, IL-6, MAPK1, TP53, and PTGS2) and six pathways (TNF signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, VEGF signaling pathway, and MAPK signaling pathway).

Conclusion: This study explored the pharmacological activity and molecular mechanisms of ZGY against male infertility from a holistic perspective. The underlying molecular mechanisms were closely related to the intervention of oxidative stress and apoptosis with CASP3, TP53, AKT1, and MAPK1 being possible targets.

Keywords: Network pharmacology, male infertility, zuogui yin, traditional chinese medicine, GO, KEGG.

« Previous Next »
[1]
Lotti, F.; Maggi, M. Sexual dysfunction and male infertility. Nat. Rev. Urol., 2018, 15(5), 287-307.
[http://dx.doi.org/10.1038/nrurol.2018.20] [PMID: 29532805]
[2]
Barratt, C.L.R.; Björndahl, L.; De Jonge, C.J.; Lamb, D.J.; Osorio Martini, F.; McLachlan, R.; Oates, R.D.; van der Poel, S.; St John, B.; Sigman, M.; Sokol, R.; Tournaye, H. The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities. Hum. Reprod. Update, 2017, 23(6), 660-680.
[http://dx.doi.org/10.1093/humupd/dmx021] [PMID: 28981651]
[3]
Vander Borght, M.; Wyns, C. Fertility and infertility: Definition and epidemiology. Clin. Biochem., 2018, 62, 2-10.
[http://dx.doi.org/10.1016/j.clinbiochem.2018.03.012] [PMID: 29555319]
[4]
Levine, H.; Jørgensen, N.; Martino-Andrade, A.; Mendiola, J.; Weksler-Derri, D.; Mindlis, I.; Pinotti, R.; Swan, S.H. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum. Reprod. Update, 2017, 23(6), 646-659.
[http://dx.doi.org/10.1093/humupd/dmx022] [PMID: 28981654]
[5]
Cannarella, R.; Condorelli, R.A.; Mongioì, L.M.; Barbagallo, F.; Calogero, A.E.; La Vignera, S. Effects of the selective estrogen receptor modulators for the treatment of male infertility: a systematic review and meta-analysis. Expert Opin. Pharmacother., 2019, 20(12), 1517-1525.
[http://dx.doi.org/10.1080/14656566.2019.1615057] [PMID: 31120775]
[6]
Schlegel, P.N. Aromatase inhibitors for male infertility. Fertil. Steril., 2012, 98(6), 1359-1362.
[http://dx.doi.org/10.1016/j.fertnstert.2012.10.023] [PMID: 23103016]
[7]
Dyer, S.; Chambers, G.M.; de Mouzon, J.; Nygren, K.G.; Zegers-Hochschild, F.; Mansour, R.; Ishihara, O.; Banker, M.; Adamson, G.D. International committee for monitoring assisted reproductive technologies world report: assisted reproductive technology 2008, 2009 and 2010. Hum. Reprod., 2016, 31(7), 1588-1609.
[http://dx.doi.org/10.1093/humrep/dew082] [PMID: 27207175]
[8]
Yin, H.; Wang, S.; Zhang, Y.; Wu, M.; Wang, J.; Ma, Y. Zuogui Pill improves the dexamethasone-induced osteoporosis progression in zebrafish larvae. Biomed. Pharmacother., 2018, 97, 995-999.
[http://dx.doi.org/10.1016/j.biopha.2017.11.029] [PMID: 29136778]
[9]
Peng, H.; Zeng, L.; Zhu, L.; Luo, S.; Xu, L.; Zeng, L.; Li, J.; Liang, Q.; Geng, H. Zuogui Pills inhibit mitochondria-dependent apoptosis of follicles in a rat model of premature ovarian failure. J. Ethnopharmacol., 2019, 238111855
[http://dx.doi.org/10.1016/j.jep.2019.111855] [PMID: 30953821]
[10]
Yao, Z.Y.; Wan, Q.; Lu, H.; Liu, X. [Effects of Zuogui pill, Yougui pill and relative compositions on differentiation towards germ cells of mouse embryonic stem cell 1B10]. Zhongguo Zhongyao Zazhi, 2015, 40(3), 495-500.
[PMID: 26084176]
[11]
Gu, S.; Xue, Y.; Zhang, Y.; Chen, K.; Xue, S.; Pan, J.; Tang, Y.; Zhu, H.; Wu, H.; Dou, D. An investigation of the mechanism of rapid relief of ulcerative colitis induced by Five-Flavor Sophora flavescens Enteric-Coated Capsules based on network pharmacology. Comb. Chem. High Throughput Screen., 2020, 23(3), 239-252.
[http://dx.doi.org/10.2174/1386207323666200302121711] [PMID: 32116186]
[12]
Zhao, H.; Shan, Y.; Ma, Z.; Yu, M.; Gong, B. A network pharmacology approach to explore active compounds and pharmacological mechanisms of epimedium for treatment of premature ovarian insufficiency. Drug Des. Devel. Ther., 2019, 13, 2997-3007.
[http://dx.doi.org/10.2147/DDDT.S207823] [PMID: 31692519]
[13]
He, D.; Huang, J.H.; Zhang, Z.Y.; Du, Q.; Peng, W.J.; Yu, R.; Zhang, S.F.; Zhang, S.H.; Qin, Y.H. A network pharmacology-based strategy for predicting active ingredients and potential targets of liuwei dihuang pill in treating type 2 diabetes mellitus. Drug Des. Devel. Ther., 2019, 13, 3989-4005.
[http://dx.doi.org/10.2147/DDDT.S216644] [PMID: 31819371]
[14]
Gao, L.; Wang, X.D.; Niu, Y.Y.; Duan, D.D.; Yang, X.; Hao, J.; Zhu, C.H.; Chen, D.; Wang, K.X.; Qin, X.M.; Wu, X.Z. Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology. Sci. Rep., 2016, 6, 24944.
[http://dx.doi.org/10.1038/srep24944] [PMID: 27143508]
[15]
Liu, Z.; Guo, F.; Wang, Y.; Li, C.; Zhang, X.; Li, H.; Diao, L.; Gu, J.; Wang, W.; Li, D.; He, F. BATMAN-TCM: a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine. Sci. Rep., 2016, 6, 21146.
[http://dx.doi.org/10.1038/srep21146] [PMID: 26879404]
[16]
Huang, J.; Cheung, F.; Tan, H.Y.; Hong, M.; Wang, N.; Yang, J.; Feng, Y.; Zheng, Q. Identification of the active compounds and significant pathways of yinchenhao decoction based on network pharmacology. Mol. Med. Rep., 2017, 16(4), 4583-4592.
[http://dx.doi.org/10.3892/mmr.2017.7149] [PMID: 28791364]
[17]
Qu, Y.; Zhang, Z.; Lu, Y. De.; Wei, Y. Network pharmacology reveals the molecular mechanism of cuyuxunxi prescription in promoting wound healing in patients with anal fistula. Evid. Based Complement. Alternat. Med., 2019, 20193865121
[http://dx.doi.org/10.1155/2019/3865121] [PMID: 31636684]
[18]
Xu, X.; Zhang, W.; Huang, C.; Li, Y.; Yu, H.; Wang, Y.; Duan, J.; Ling, Y. A novel chemometric method for the prediction of human oral bioavailability. Int. J. Mol. Sci., 2012, 13(6), 6964-6982.
[http://dx.doi.org/10.3390/ijms13066964] [PMID: 22837674]
[19]
Zhang, S.N.; Li, X.Z.; Yang, X.Y. Drug-likeness prediction of chemical constituents isolated from Chinese materia medica Ciwujia. J. Ethnopharmacol., 2017, 198, 131-138.
[http://dx.doi.org/10.1016/j.jep.2017.01.002] [PMID: 28065780]
[20]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[21]
Law, V.; Knox, C.; Djoumbou, Y.; Jewison, T.; Guo, A.C.; Liu, Y.; Maciejewski, A.; Arndt, D.; Wilson, M.; Neveu, V.; Tang, A.; Gabriel, G.; Ly, C.; Adamjee, S.; Dame, Z.T.; Han, B.; Zhou, Y.; Wishart, D.S. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res., 2014, 42, D1091-D1097.
[http://dx.doi.org/10.1093/nar/gkt1068] [PMID: 24203711]
[22]
Kuhn, M.; Szklarczyk, D.; Franceschini, A.; von Mering, C.; Jensen, L.J.; Bork, P. STITCH 3: zooming in on protein-chemical interactions. Nucleic Acids Res., 2012, 40, D876-D880.
[http://dx.doi.org/10.1093/nar/gkr1011] [PMID: 22075997]
[23]
The UniProt Consortium. UniProt: the universal protein knowledgebase. Nucleic Acids Res., 2017, 45(D1), D158-D169.
[http://dx.doi.org/10.1093/nar/gkw1099] [PMID: 27899622]
[24]
Boyadjiev, S.A.; Jabs, E.W. Online Mendelian Inheritance in Man (OMIM) as a knowledgebase for human developmental disorders. Clin. Genet., 2000, 57(4), 253-266.
[http://dx.doi.org/10.1034/j.1399-0004.2000.570403.x] [PMID: 10845565]
[25]
Stelzer, G.; Plaschkes, I.; Oz-Levi, D.; Alkelai, A.; Olender, T.; Zimmerman, S.; Twik, M.; Belinky, F.; Fishilevich, S.; Nudel, R.; Guan-Golan, Y.; Warshawsky, D.; Dahary, D.; Kohn, A.; Mazor, Y.; Kaplan, S.; Iny Stein, T.; Baris, H.N.; Rappaport, N.; Safran, M.; Lancet, D. VarElect: the phenotype-based variation prioritizer of the GeneCards Suite. BMC Genomics, 2016, 17(Suppl. 2), 444.
[http://dx.doi.org/10.1186/s12864-016-2722-2] [PMID: 27357693]
[26]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[27]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[28]
Lu, H.C.; Yao, J.Q.; Yang, X.; Han, J.; Wang, J.Z.; Xu, K.; Zhou, R.; Yu, H.; Lv, Q.; Gu, M. Identification of a potentially functional circRNA-miRNA-mRNA regulatory network for investigating pathogenesis and providing possible biomarkers of bladder cancer. Cancer Cell Int., 2020, 20, 31.
[http://dx.doi.org/10.1186/s12935-020-1108-3] [PMID: 32015691]
[29]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[30]
Primmer, C.R.; Papakostas, S.; Leder, E.H.; Davis, M.J.; Ragan, M.A. Annotated genes and nonannotated genomes: cross-species use of Gene Ontology in ecology and evolution research. Mol. Ecol., 2013, 22(12), 3216-3241.
[http://dx.doi.org/10.1111/mec.12309] [PMID: 23763602]
[31]
Kanehisa, M.; Furumichi, M.; Tanabe, M.; Sato, Y.; Morishima, K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res., 2017, 45(D1), D353-D361.
[http://dx.doi.org/10.1093/nar/gkw1092] [PMID: 27899662]
[32]
Xu, W.M.; Yang, K.; Jiang, L.J.; Hu, J.Q.; Zhou, X.Z. Integrated modules analysis to explore the molecular mechanisms of phlegm-stasis cementation syndrome with ischemic heart disease. Front. Physiol., 2018, 9, 7.
[http://dx.doi.org/10.3389/fphys.2018.00007] [PMID: 29403392]
[33]
Le Goff, M.; Le Ferrec, E.; Mayer, C.; Mimouni, V.; Lagadic-Gossmann, D.; Schoefs, B.; Ulmann, L. Microalgal carotenoids and phytosterols regulate biochemical mechanisms involved in human health and disease prevention. Biochimie, 2019, 167, 106-118.
[http://dx.doi.org/10.1016/j.biochi.2019.09.012] [PMID: 31545993]
[34]
Yadav, M.; Parle, M.; Jindal, D.K.; Dhingra, S. Protective effects of stigmasterol against ketamine-induced psychotic symptoms: Possible behavioral, biochemical and histopathological changes in mice. Pharmacol. Rep., 2018, 70(3), 591-599.
[http://dx.doi.org/10.1016/j.pharep.2018.01.001] [PMID: 29679883]
[35]
Zhu, Q.; Liu, M.; He, Y.; Yang, B. Quercetin protect cigarette smoke extracts induced inflammation and apoptosis in RPE cells. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 2010-2015.
[http://dx.doi.org/10.1080/21691401.2019.1608217] [PMID: 31122072]
[36]
Liao, P.C.; Lai, M.H.; Hsu, K.P.; Kuo, Y.H.; Chen, J.; Tsai, M.C.; Li, C.X.; Yin, X.J.; Jeyashoke, N.; Chao, L.K. Identification of β-sitosterol as in vitro anti-inflammatory constituent in Moringa oleifera. J. Agric. Food Chem., 2018, 66(41), 10748-10759.
[http://dx.doi.org/10.1021/acs.jafc.8b04555] [PMID: 30280897]
[37]
Lin, Y.; Knol, D.; Menéndez-Carreño, M.; Baris, R.; Janssen, H.G.; Trautwein, E.A. Oxidation of sitosterol and campesterol in foods upon cooking with liquid margarines without and with added plant sterol esters. Food Chem., 2018, 241, 387-396.
[http://dx.doi.org/10.1016/j.foodchem.2017.08.118] [PMID: 28958544]
[38]
O’Hara, L.; Smith, L.B. Androgen receptor roles in spermatogenesis and infertility. Best Pract. Res. Clin. Endocrinol. Metab., 2015, 29(4), 595-605.
[http://dx.doi.org/10.1016/j.beem.2015.04.006] [PMID: 26303086]
[39]
Zhao, Z.; Qiao, L.; Dai, Z.; He, Q.; Lan, X.; Huang, S.; He, L. LncNONO-AS regulates AR expression by mediating NONO. Theriogenology, 2020, 145, 198-206.
[http://dx.doi.org/10.1016/j.theriogenology.2019.10.025] [PMID: 31732162]
[40]
Tournaye, H.; Krausz, C.; Oates, R.D. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol., 2017, 5(7), 544-553.
[http://dx.doi.org/10.1016/S2213-8587(16)30040-7] [PMID: 27395771]
[41]
Xiao, J. Dietary flavonoid aglycones and their glycosides: Which show better biological significance? Crit. Rev. Food Sci. Nutr., 2017, 57(9), 1874-1905.
[http://dx.doi.org/10.1080/10408398.2015.1032400] [PMID: 26176651]
[42]
Diao, R.; Gan, H.; Tian, F.; Cai, X.; Zhen, W.; Song, X.; Duan, Y.G. In vitro antioxidation effect of Quercetin on sperm function from the infertile patients with leukocytospermia. Am. J. Reprod. Immunol., 2019, 82(3), e13155.
[http://dx.doi.org/10.1111/aji.13155] [PMID: 31166052]
[43]
Yelumalai, S.; Giribabu, N.; Karim, K.; Omar, S.Z.; Salleh, N.B. In vivo administration of quercetin ameliorates sperm oxidative stress, inflammation, preserves sperm morphology and functions in streptozotocin-nicotinamide induced adult male diabetic rats. Arch. Med. Sci., 2019, 15(1), 240-249.
[http://dx.doi.org/10.5114/aoms.2018.81038] [PMID: 30697276]
[44]
Zhang, Y.; Song, M.; Rui, X.; Pu, S.; Li, Y.; Li, C. Supplemental dietary phytosterin protects against 4-nitrophenol-induced oxidative stress and apoptosis in rat testes. Toxicol. Rep., 2015, 2, 664-676.
[http://dx.doi.org/10.1016/j.toxrep.2015.04.007] [PMID: 28962402]
[45]
Almeida, C.; Cunha, M.; Ferraz, L.; Silva, J.; Barros, A.; Sousa, M. Caspase-3 detection in human testicular spermatozoa from azoospermic and non-azoospermic patients. Int. J. Androl., 2011, 34(5 Pt 2), e407-e414.
[http://dx.doi.org/10.1111/j.1365-2605.2011.01151.x] [PMID: 21812785]
[46]
Moradi, M.N.; Karimi, J.; Khodadadi, I.; Amiri, I.; Karami, M.; Saidijam, M.; Vatannejad, A.; Tavilani, H. Evaluation of the p53 and Thioredoxin reductase in sperm from asthenozoospermic males in comparison to normozoospermic males. Free Radic. Biol. Med., 2018, 116, 123-128.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.12.038] [PMID: 29305108]
[47]
Yu, L.; Yang, X.; Ma, B.; Ying, H.; Shang, X.; He, B.; Zhang, Q. Abnormal arachidonic acid metabolic network may reduce sperm motility via P38 MAPK. Open Biol., 2019, 9(4), 180091.
[http://dx.doi.org/10.1098/rsob.180091] [PMID: 31014201]
[48]
Fruman, D.A.; Chiu, H.; Hopkins, B.D.; Bagrodia, S.; Cantley, L.C.; Abraham, R.T. The PI3K pathway in human disease. Cell, 2017, 170(4), 605-635.
[http://dx.doi.org/10.1016/j.cell.2017.07.029] [PMID: 28802037]
[49]
Huang, W.; Cao, Z.; Zhang, J.; Ji, Q.; Li, Y. Aflatoxin B1 promotes autophagy associated with oxidative stress-related PI3K/AKT/mTOR signaling pathway in mice testis. Environ. Pollut., 2019, 255(Pt 2)113317
[http://dx.doi.org/10.1016/j.envpol.2019.113317] [PMID: 31610502]
[50]
Yang, Z.Y.; Qian, L.L.; Xu, Y.; Song, M.T.; Liu, C.; Han, R.M.; Zhang, J.P.; Skibsted, L.H. Kinetic studies on radical scavenging activity of kaempferol decreased by sn(ii) binding. Molecules, 2020, 25(8), E1975.
[http://dx.doi.org/10.3390/molecules25081975] [PMID: 32340303]
[51]
Rana, S.; Sarmah, S.; Singha Roy, A.; Ghosh, K.S. Elucidation of molecular interactions between human γD-crystallin and quercetin, an inhibitor against tryptophan oxidation. J. Biomol. Struct. Dyn., 2020, 25(8), 1975.
[http://dx.doi.org/10.1080/07391102.2020.1738960] [PMID: 32131700]

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