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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

A Network Pharmacology Study on the Similarities and Differences in the Mechanisms of Zuo Gui Wan/You Gui Wan for the Treatment of Premature Ovarian Failure

Author(s): Shanshan Mei, Chaoqin Yu*, Jie Ding and Wen Cheng

Volume 26, Issue 6, 2023

Published on: 18 October, 2022

Page: [1167 - 1179] Pages: 13

DOI: 10.2174/1386207325666220602114701

Price: $65

Abstract

Background: Premature ovarian failure is a heterogeneous disease that severely affects the quality of life of women in their reproductive years. The ancient classical Chinese medicine compounds Zuo Gui Wan and You Gui Wan have great potential to treat premature ovarian failure, but the similarities and differences in their pharmacological mechanisms for treating POF are not yet clear.

Methods: In this study, the public database was used to screen the active ingredients and potential targets of Zuo Gui Wan and You Gui Wan. The similarities and differences in the potential targets of both pills for the treatment of POF were analysed using the POF-related genes obtained from OMIM and GeneCards. The protein-protein interaction network was established and collated to form a drug-active ingredient-target gene network using STRING. Finally, the drug-target-pathway network was constructed by enrichment analysis to find the differences in target enrichment on the same pathway.

Results: Pharmacological analysis of the network showed that Zuo Gui Wan contains 72 active ingredients, while You Gui Wan has 112. A total of 62 common compositions, such as quercetin and kaempferol, were identified. Amongst them were 10 unique compounds, such as hydroxyproline and cholesterol, in Zuo Gui Wan and 50 exclusive compounds, such as Karanjin and betacarotene, in You Gui Wan. In addition, 14 overlapping targets, including MAPK1, CXCL8, TNF, IL6, and EGFR, were determined amongst the first 20 targets in the treatment of POF by both pills, demonstrating that the core mechanism of POF treatment is similar between the two. Pathway enrichment analysis showed 87 identical and significant pathways between Zuo Gui Wan and You Gui Wan, including IL-17, TNF, PI3K-Akt, oestrogen, VEGF, and other pathways. Zuo Gui Wan has 12 special pathways, such as natural killer cell-mediated cytotoxicity and intestinal immune network for IgA production. You Gui Wan has nine unique pathways, such as insulin secretion and glucagon signalling pathway.

Conclusion: Zuo Gui Wan and You Gui Wan could treat POF by inhibiting oxidative stress and inflammation, regulating hormone levels, improving ovarian function, and promoting follicular development. Zuo Gui Wan is inclined to immune regulation, while You Gui Wan prefers insulin regulation. Therefore, similarities and differences clearly exist in the specific mechanisms of Zuo Gui Wan and You Gui Wan in the treatment of POF.

Keywords: Premature ovarian failure, Zuo Gui Wan, You Gui Wan, network pharmacology menopause, oestrogen, glucagon signalling pathway.

[1]
Fu, Y.X.; Ji, J.; Shan, F.; Li, J.; Hu, R. Human mesenchymal stem cell treatment of premature ovarian failure: New challenges and opportunities. Stem Cell Res. Ther., 2021, 12(1), 161.
[http://dx.doi.org/10.1186/s13287-021-02212-0] [PMID: 33658073]
[2]
Lew, R. Natural history of ovarian function including assessment of ovarian reserve and premature ovarian failure. Best Pract. Res. Clin. Obstet. Gynaecol., 2019, 55, 2-13.
[http://dx.doi.org/10.1016/j.bpobgyn.2018.05.005] [PMID: 30420162]
[3]
Sullivan, S.D.; Sarrel, P.M.; Nelson, L.M. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil. Steril., 2016, 106(7), 1588-1599.
[http://dx.doi.org/10.1016/j.fertnstert.2016.09.046] [PMID: 27912889]
[4]
Lin, J.; Wu, D.; Jia, L.; Liang, M.; Liu, S.; Qin, Z.; Zhang, J.; Han, Y.; Liu, S.; Zhang, Y. The treatment of complementary and alternative medicine on premature ovarian failure. Evid. Based Complement. Alternat. Med., 2021, 2021, 6677767.
[http://dx.doi.org/10.1155/2021/6677767] [PMID: 33936242]
[5]
Kou, M.J.; Ding, X.F.; Chen, J.X.; Liu, Y.; Liu, Y.Y. Traditional chinese medicine combined with hormone therapy to treat premature ovarian failure: A meta-analysis of randomized controlled trials. Afr. J. Tradit. Complement. Altern. Med., 2016, 13(5), 160-169.
[PMID: 28487907]
[6]
Li, J.; Sun, K.; Qi, B.; Feng, G.; Wang, W.; Sun, Q.; Zheng, C.; Wei, X.; Jia, Y. An evaluation of the effects and safety of Zuogui pill for treating osteoporosis: Current evidence for an ancient Chinese herbal formula. Phytother. Res., 2021, 35(4), 1754-1767.
[http://dx.doi.org/10.1002/ptr.6908] [PMID: 33089589]
[7]
Gu, F.; Jiang, J.; Wang, S.; Feng, T.; Zhou, Y.; Ma, Y.; Shen, S. An experimental research into the potential therapeutic effects of anti-osteoporosis decoction and yougui pill on ovariectomy-induced osteoporosis. Am. J. Transl. Res., 2019, 11(9), 6032-6039.
[PMID: 31632571]
[8]
Lin, J.; Li, X.L.; Song, H.; Li, Q.; Wang, M.Y.; Qiu, X.M.; Li, D.J.; Wang, L. A general description for Chinese medicine in treating premature ovarian failure. Chin. J. Integr. Med., 2017, 23(2), 91-97.
[http://dx.doi.org/10.1007/s11655-016-2642-7] [PMID: 28265850]
[9]
Zhu, L.; Luo, S.P.; Xu, L.M. Protective effect of zuogui pill on ovarian autoimmune injury. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 2005, 25(10), 920-924.
[PMID: 16313118]
[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]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[12]
Luo, T.T.; Lu, Y.; Yan, S.K.; Xiao, X.; Rong, X.L.; Guo, J. Network pharmacology in research of Chinese medicine formula: Methodology, application and prospective. Chin. J. Integr. Med., 2020, 26(1), 72-80.
[http://dx.doi.org/10.1007/s11655-019-3064-0] [PMID: 30941682]
[13]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. 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]
[14]
Xue, R.; Fang, Z.; Zhang, M.; Yi, Z.; Wen, C.; Shi, T. TCMID: Traditional Chinese medicine integrative database for herb molecular mechanism analysis. Nucleic Acids Res., 2013, 41(Database issue), D1089-D1095.
[PMID: 23203875]
[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(1), 21146.
[http://dx.doi.org/10.1038/srep21146] [PMID: 26879404]
[16]
Huang, C.; Zheng, C.; Li, Y.; Wang, Y.; Lu, A.; Yang, L. Systems pharmacology in drug discovery and therapeutic insight for herbal medicines. Brief. Bioinform., 2014, 15(5), 710-733.
[http://dx.doi.org/10.1093/bib/bbt035] [PMID: 23736100]
[17]
Wang, Z.; Liang, L.; Yin, Z.; Lin, J. Improving chemical similarity ensemble approach in target prediction. J. Cheminform., 2016, 8(1), 20.
[http://dx.doi.org/10.1186/s13321-016-0130-x] [PMID: 27110288]
[18]
Rebhan, M.; Chalifa-Caspi, V.; Prilusky, J.; Lancet, D. GeneCards: A novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics, 1998, 14(8), 656-664.
[http://dx.doi.org/10.1093/bioinformatics/14.8.656] [PMID: 9789091]
[19]
Amberger, J.S.; Bocchini, C.A.; Schiettecatte, F.; Scott, A.F.; Hamosh, A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res., 2015, 43(Database issue), D789-D798.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[20]
Altaf-Ul-Amin, M.; Shinbo, Y.; Mihara, K.; Kurokawa, K.; Kanaya, S. Development and implementation of an algorithm for detection of protein complexes in large interaction networks. BMC Bioinformatics, 2006, 7(1), 207.
[http://dx.doi.org/10.1186/1471-2105-7-207] [PMID: 16613608]
[21]
Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol., 2003, 4(5), 3.
[http://dx.doi.org/10.1186/gb-2003-4-5-p3] [PMID: 12734009]
[22]
Ghahremani-Nasab, M.; Ghanbari, E.; Jahanbani, Y.; Mehdizadeh, A.; Yousefi, M. Premature ovarian failure and tissue engineering. J. Cell. Physiol., 2020, 235(5), 4217-4226.
[http://dx.doi.org/10.1002/jcp.29376] [PMID: 31663142]
[23]
The, L.O. Rethinking traditional Chinese medicines for cancer. Lancet Oncol., 2015, 16(15), 1439.
[http://dx.doi.org/10.1016/S1470-2045(15)00406-4] [PMID: 26545833]
[24]
Liu, T.; Ding, Y.; Wen, A. Traditional Chinese medicine for ischaemic stroke. Lancet Neurol., 2018, 17(9), 745.
[http://dx.doi.org/10.1016/S1474-4422(18)30290-4] [PMID: 30129474]
[25]
D’Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia, 2015, 106, 256-271.
[http://dx.doi.org/10.1016/j.fitote.2015.09.018] [PMID: 26393898]
[26]
Li, Y.; Yao, J.; Han, C.; Yang, J.; Chaudhry, M.T.; Wang, S.; Liu, H.; Yin, Y. Quercetin, inflammation and immunity. Nutrients, 2016, 8(3), 167.
[http://dx.doi.org/10.3390/nu8030167] [PMID: 26999194]
[27]
Costa, L.G.; Garrick, J.M.; Roquè, P.J.; Pellacani, C. Mechanisms of neuroprotection by quercetin: Counteracting oxidative stress and more. Oxid. Med. Cell. Longev., 2016, 2016, 2986796.
[http://dx.doi.org/10.1155/2016/2986796] [PMID: 26904161]
[28]
Verma, P.; K Sharma, A.; Shankar, H.; Sharma, A.; Rao, D.N. Role of trace elements, oxidative stress and immune system: A triad in premature ovarian failure. Biol. Trace Elem. Res., 2018, 184(2), 325-333.
[http://dx.doi.org/10.1007/s12011-017-1197-6] [PMID: 29181820]
[29]
Kumar, M.; Pathak, D.; Venkatesh, S.; Kriplani, A.; Ammini, A.C.; Dada, R. Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF). Indian J. Med. Res., 2012, 135(1), 92-97.
[http://dx.doi.org/10.4103/0971-5916.93430] [PMID: 22382189]
[30]
Jiao, J.; Shi, B.; Wang, T.; Fang, Y.; Cao, T.; Zhou, Y.; Wang, X.; Li, D. Characterization of long non-coding RNA and messenger RNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with polycystic ovary syndrome. Hum. Reprod., 2018, 33(9), 1735-1748.
[http://dx.doi.org/10.1093/humrep/dey255] [PMID: 30052945]
[31]
Brown, C.; LaRocca, J.; Pietruska, J.; Ota, M.; Anderson, L.; Smith, S.D.; Weston, P.; Rasoulpour, T.; Hixon, M.L. Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1. Biol. Reprod., 2010, 82(2), 246-256.
[http://dx.doi.org/10.1095/biolreprod.109.077925] [PMID: 19794155]
[32]
Liu, T.E.; Zhang, L.; Wang, S.; Chen, C.; Zheng, J. Tripterygium glycosides induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway. Exp. Ther. Med., 2015, 10(1), 12-18.
[http://dx.doi.org/10.3892/etm.2015.2498] [PMID: 26170905]
[33]
Gasperin, B.G.; Rovani, M.T.; Ferreira, R.; Ilha, G.F.; Bordignon, V.; Gonçalves, P.B.; Duggavathi, R. Functional status of STAT3 and MAPK3/1 signaling pathways in granulosa cells during bovine follicular deviation. Theriogenology, 2015, 83(3), 353-359.
[http://dx.doi.org/10.1016/j.theriogenology.2014.09.026] [PMID: 25442017]
[34]
Grossmann, B.; Saur, S.; Rall, K.; Pecher, A.C.; Hübner, S.; Henes, J.; Henes, M. Prevalence of autoimmune disease in women with premature ovarian failure. Eur. J. Contracept. Reprod. Health Care, 2020, 25(1), 72-75.
[http://dx.doi.org/10.1080/13625187.2019.1702638] [PMID: 31852274]
[35]
Košir Pogačnik, R.; Meden Vrtovec, H.; Vizjak, A.; Uršula Levičnik, A.; Slabe, N.; Ihan, A. Possible role of autoimmunity in patients with premature ovarian insufficiency. Int. J. Fertil. Steril., 2014, 7(4), 281-290.
[PMID: 24520498]
[36]
Yin, N.; Wang, Y.; Lu, X.; Liu, R.; Zhang, L.; Zhao, W.; Yuan, W.; Luo, Q.; Wu, H.; Luan, X.; Zhang, H. hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway. Stem Cell Res. Ther., 2018, 9(1), 37.
[http://dx.doi.org/10.1186/s13287-018-0772-x] [PMID: 29444704]
[37]
Kalantaridou, S.N.; Naka, K.K.; Bechlioulis, A.; Makrigiannakis, A.; Michalis, L.; Chrousos, G.P. Premature ovarian failure, endothelial dysfunction and estrogen-progestogen replacement. Trends Endocrinol. Metab., 2006, 17(3), 101-109.
[http://dx.doi.org/10.1016/j.tem.2006.02.003] [PMID: 16515863]
[38]
De Vincentis, S.; Monzani, M.L.; Brigante, G. Crosstalk between gonadotropins and thyroid axis. Minerva Ginecol., 2018, 70(5), 609-620.
[http://dx.doi.org/10.23736/S0026-4784.18.04271-5] [PMID: 29999286]
[39]
Leder, B.Z. Parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis therapy. Curr. Osteoporos. Rep., 2017, 15(2), 110-119.
[http://dx.doi.org/10.1007/s11914-017-0353-4] [PMID: 28303448]
[40]
Xiaofeng, X.; Yong, T.; Guorong, J.; Xuanyi, C.; Rensheng, L.; Lurong, Z.; Guoqiang, L. Effects of bushen tianjing recipe in a rat model of tripterygium glycoside-induced premature ovarian failure. BioMed Central, 2017, 12, 1.
[41]
Tuohy, V.K.; Altuntas, C.Z. Autoimmunity and premature ovarian failure. Curr. Opin. Obstet. Gynecol., 2007, 19(4), 366-369.
[http://dx.doi.org/10.1097/GCO.0b013e328220e90c] [PMID: 17625420]
[42]
Fénichel, P.; Sosset, C.; Barbarino-Monnier, P.; Gobert, B.; Hiéronimus, S.; Béné, M.C.; Harter, M. Prevalence, specificity and significance of ovarian antibodies during spontaneous premature ovarian failure. Hum. Reprod., 1997, 12(12), 2623-2628.
[http://dx.doi.org/10.1093/humrep/12.12.2623] [PMID: 9455825]
[43]
Thaiss, C.A.; Zmora, N.; Levy, M.; Elinav, E. The microbiome and innate immunity. Nature, 2016, 535(7610), 65-74.
[http://dx.doi.org/10.1038/nature18847] [PMID: 27383981]
[44]
Soto, N.; Iñiguez, G.; López, P.; Larenas, G.; Mujica, V.; Rey, R.A.; Codner, E. Anti-Mullerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1 diabetes mellitus. Hum. Reprod., 2009, 24(11), 2838-2844.
[http://dx.doi.org/10.1093/humrep/dep276] [PMID: 19643804]
[45]
Wang, F.; Wang, S.; Zhang, Z.; Lin, Q.; Liu, Y.; Xiao, Y.; Xiao, K.; Wang, Z. Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. Mol. Med. Rep., 2017, 16(6), 8164-8170.
[http://dx.doi.org/10.3892/mmr.2017.7678] [PMID: 28990055]
[46]
Kwintkiewicz, J.; Giudice, L.C. The interplay of insulin-like growth factors, gonadotropins, and endocrine disruptors in ovarian follicular development and function. Semin. Reprod. Med., 2009, 27(1), 43-51.
[http://dx.doi.org/10.1055/s-0028-1108009] [PMID: 19197804]
[47]
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, 238, 111855.
[http://dx.doi.org/10.1016/j.jep.2019.111855] [PMID: 30953821]

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