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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Integration of LC-LTQ-Orbitrap-MS and Network Pharmacology to Analyze the Active Components of Sijunzi Decoction and their Mechanism of Action Against Cytotoxicity-associated Premature Ovarian Insufficiency

Author(s): Yiying Chen, Sixuan Han, An Kang, Rui Fu, Li Chen, Jinrui Guo* and Qiong Wang*

Volume 26, Issue 14, 2023

Published on: 05 May, 2023

Page: [2437 - 2451] Pages: 15

DOI: 10.2174/1386207326666230303094247

Price: $65

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Abstract

Introduction: Sijunzi Decoction (SJZD) is a classical prescription in traditional Chinese medicine that enhances neuroimmune endocrine function to alleviate inflammatory aging, a key pathogenic mechanism underlying premature ovarian insufficiency (POI). However, the mechanism through which SJZD alleviates POI remains unknown. Hence, we aimed to identify the active components of SJZD and its mechanism of therapeutic action against POI.

Methods: We identified compounds in SJZD using liquid chromatography-linear trap quadrupole- Orbitrap-mass spectrometry (LC-LTQ-Orbitrap-MS). Traditional Chinese Medicine Systems (TCMSP) and HERB databases were used to identify the ingredients and potential targets of SJZD. We analyzed Gene Ontology (GO) terms and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using RStudio and constructed a visual network using Cytoscape3.9.1.

Results: We identified 98 compounds using LC-LTQ-Orbitrap-MS, among which 29 were bioactive. The screen outputted yielded 151 predicted targets of these compounds that were associated with POI. The results of the GO and KEGG analyses showed that these compounds play key roles in cell growth, division, migration, and survival signaling pathways. Therefore, phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and epidermal growth factor receptor (EGFR) pathways might be closely associated with the pharmacological effects of SJZD on the pathological processes of POI.

Conclusion: Our findings provide a scientific basis for rapidly analyzing bioactive compounds in SJZD and their pharmacological mechanisms.

Graphical Abstract

[1]
Chon, S.J.; Umair, Z.; Yoon, M.S. Premature ovarian insufficiency: Past, present, and future. Front. Cell Dev. Biol., 2021, 9, 672890.
[http://dx.doi.org/10.3389/fcell.2021.672890] [PMID: 34041247]
[2]
Panay, N. Progress in understanding and management of premature ovarian insufficiency. Climacteric, 2021, 24(5), 423-424.
[http://dx.doi.org/10.1080/13697137.2021.1919460] [PMID: 34498504]
[3]
Stevenson, J.C.; Collins, P.; Hamoda, H.; Lambrinoudaki, I.; Maas, A.H.E.M.; Maclaran, K.; Panay, N. Cardiometabolic health in premature ovarian insufficiency. Climacteric, 2021, 24(5), 474-480.
[http://dx.doi.org/10.1080/13697137.2021.1910232] [PMID: 34169795]
[4]
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]
[5]
Upton, C.E.; Daniels, J.P.; Davies, M.C. Premature ovarian insufficiency: The need for evidence on the effectiveness of hormonal therapy. Climacteric, 2021, 24(5), 453-458.
[http://dx.doi.org/10.1080/13697137.2021.1902496] [PMID: 33928827]
[6]
Xu, X.; Jones, M.; Mishra, G.D. Age at natural menopause and development of chronic conditions and multimorbidity: Results from an Australian prospective cohort. Hum. Reprod., 2020, 35(1), 203-211.
[http://dx.doi.org/10.1093/humrep/dez259] [PMID: 31955198]
[7]
Fu, Y.; Ding, D.N.; Shen, Y.; Jia, L.Y.; Yan, M.Y.; Wei, W.; Song, C.H.; Han, F.J. Complementary and alternative medicine for premature ovarian insufficiency: A review of utilization and mechanisms. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-15.
[http://dx.doi.org/10.1155/2022/9053930] [PMID: 35399635]
[8]
Li, M.; Xie, L.; Li, Y.; Liu, J.; Nie, G.; Yang, H. Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice. Chin. Med., 2020, 15(1), 83.
[http://dx.doi.org/10.1186/s13020-020-00362-6] [PMID: 32774448]
[9]
Wang, L.; Li, M.; Liu, J.; Nie, G.; Li, Y.; Yang, H. Protective effect of Huyang Yangkun Formula on ovarian function in premature ovarian insufficiency rats based on apoptotic mechanism. J. Ethnopharmacol., 2021, 280, 114477.
[http://dx.doi.org/10.1016/j.jep.2021.114477] [PMID: 34343645]
[10]
Xie, L.; Wu, S.; Cao, D.; Li, M.; Liu, J.; Nie, G.; Li, Y.; Yang, H. Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo-JAK2/STAT3 signaling pathway. Biomed. Pharmacother., 2019, 116, 109008.
[http://dx.doi.org/10.1016/j.biopha.2019.109008] [PMID: 31152926]
[11]
Cai, J.; Wang, H.; Zhou, S.; Wu, B.; Song, H.R.; Xuan, Z.R. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. J. Chin. Integr. Med., 2008, 6(1), 37-40.
[http://dx.doi.org/10.3736/jcim20080108] [PMID: 18184544]
[12]
Chen, Y.; Deng, J.; Wen, Y.; Chen, B.; Hou, J.; Peng, B.; Zhang, S.; Mi, H.; Jiang, Q.; Wu, X.; Liu, F.; Chen, X. Modified Sijunzi decoction in the treatment of ulcerative colitis in the remission phase: Study protocol for a series of N-of-1 double-blind, randomised controlled trials. Trials, 2020, 21(1), 396.
[http://dx.doi.org/10.1186/s13063-020-04315-0] [PMID: 32398112]
[13]
Jie, Y.; He, W.; Yang, X.; Chen, W. Krüppel-like factor 4 acts as a potential therapeutic target of Sijunzi decoction for treatment of colorectal cancer. Cancer Gene Ther., 2017, 24(9), 361-366.
[http://dx.doi.org/10.1038/cgt.2017.25] [PMID: 28752861]
[14]
Cheng, W.L.; Wang, X.Y.; Jiang, Z.Y.; Pan, J.Q.; Dong, J.; Kuang, S.S.; Rao, Z.L. [The immunomodulatory effects of sijunzi decoction and its disassembled prescription on D-galactose-induced aging mice] Zhong Yao Cai, 2009, 32(9), 1425-1429.
[PMID: 20034224]
[15]
Ji, Y.F.; Wang, R.J.; Li, X.B. Research progress on chemical constituents and pharmacological effects of Sijunzi decoction. Chin. Tradit. Herbal Drugs, 2016, 47(05), 837-843.
[16]
Huang, Y.; Hu, C.; Ye, H.; Luo, R.; Fu, X.; Li, X.; Huang, J.; Chen, W.; Zheng, Y. Inflamm-aging: A new mechanism affecting premature ovarian insufficiency. J. Immunol. Res., 2019, 2019, 1-7.
[http://dx.doi.org/10.1155/2019/8069898] [PMID: 30719458]
[17]
Ge, P.; Xing, N.; Ren, Y.; Zhu, L.; Han, D.; Kuang, H.; Li, J. Preventive effect of American ginseng against premature ovarian failure in a rat model. Drug Dev. Res., 2014, 75(8), 521-528.
[http://dx.doi.org/10.1002/ddr.21234] [PMID: 25424468]
[18]
Zhu, L.; Li, J.; Xing, N.; Han, D.; Kuang, H.; Ge, P. American ginseng regulates gene expression to protect against premature ovarian failure in rats. BioMed Res. Int., 2015, 2015, 1-8.
[http://dx.doi.org/10.1155/2015/767124] [PMID: 25705687]
[19]
Hou, J.; Zhou, X.; Wang, P.; Zhao, C.; Qin, Y.; Liu, F.; Yu, L.; Xu, H. An integrative pharmacology-based approach for evaluating the potential effects of purslane seed in diabetes mellitus treatment using UHPLC-LTQ-Orbitrap and TCMIP V2.0. Front. Pharmacol., 2021, 11, 593693.
[http://dx.doi.org/10.3389/fphar.2020.593693] [PMID: 33603663]
[20]
Zhang, J.; Jin, Q.; Wu, W.; Jin, X.; An, Y.; Liu, C.; Wei, W.; Li, Z.; Yao, C.; Yao, S.; Huang, Y.; Qu, H.; Song, J.; Wu, W.; Guo, D. “Force iteration molecular designing” strategy for the systematic characterization and discovery of new protostane triterpenoids from Alisma Rhizoma by UHPLC/LTQ-Orbitrap-MS. Anal. Bioanal. Chem., 2021, 413(6), 1749-1764.
[http://dx.doi.org/10.1007/s00216-020-03145-y] [PMID: 33527181]
[21]
Fang, S.; Dong, L.; Liu, L.; Guo, J.; Zhao, L.; Zhang, J.; Bu, D.; Liu, X.; Huo, P.; Cao, W.; Dong, Q.; Wu, J.; Zeng, X.; Wu, Y.; Zhao, Y. HERB: A high-throughput experiment- and reference-guided database of traditional Chinese medicine. Nucleic Acids Res., 2021, 49(D1), D1197-D1206.
[http://dx.doi.org/10.1093/nar/gkaa1063] [PMID: 33264402]
[22]
Liu, Y.; Wang, Z.; Zhao, L. A potential three-gene-based diagnostic signature for hypertension in pregnancy. Int. J. Gen. Med., 2021, 14, 6847-6856.
[http://dx.doi.org/10.2147/IJGM.S331573] [PMID: 34703289]
[23]
Zhang, J.D.; Wiemann, S. KEGGgraph: A graph approach to Kegg pathway in R and bioconductor. Bioinformatics, 2009, 25(11), 1470-1471.
[http://dx.doi.org/10.1093/bioinformatics/btp167] [PMID: 19307239]
[24]
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]
[25]
Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[26]
Liu, Y.; Yang, J.; Cai, Z. Chemical investigation on Sijunzi decoction and its two major herbs Panax ginseng and Glycyrrhiza uralensis by LC/MS/MS. J. Pharm. Biomed. Anal., 2006, 41(5), 1642-1647.
[http://dx.doi.org/10.1016/j.jpba.2006.02.033] [PMID: 16574366]
[27]
Cao, F.S.; Yu, F.; Chen, Q.H. Fragmentation pathways and content of Atractylenolide I detected in rhizome of Atractylodes macrocephala by LC-IT-MS. J. Hubei Univ. Chin. Med., 2020, 22(02), 45-48.
[28]
Wang, T.; Jiang, B.; Zeng, Y.E. Determination of content of flavonoids in single and mixed decoction of four noble ingredients. LiShiZhen Med. Mater. Medica Res., 2002, 13(09), 519-520.
[29]
Liu, H.; Yang, J.; Du, F.; Gao, X.; Ma, X.; Huang, Y.; Xu, F.; Niu, W.; Wang, F.; Mao, Y.; Sun, Y.; Lu, T.; Liu, C.; Zhang, B.; Li, C. Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats. Drug Metab. Dispos., 2009, 37(12), 2290-2298.
[http://dx.doi.org/10.1124/dmd.109.029819] [PMID: 19786509]
[30]
Yu, K.; Chen, F.; Li, C. Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: What do we know and what do we need to know more? Curr. Drug Metab., 2012, 13(5), 577-598.
[http://dx.doi.org/10.2174/1389200211209050577] [PMID: 22292787]
[31]
He, L.; Wang, X.; Cheng, D.; Xiong, Z.; Liu, X. Ginsenoside Rg1 improves pathological damages by activating the p21 p53 STK pathway in ovary and Bax Bcl2 in the uterus in premature ovarian insufficiency mouse models. Mol. Med. Rep., 2021, 23(1), 37.
[PMID: 33179093]
[32]
Du, X.Y.; Huang, J.; Xu, L.Q.; Tang, D.F.; Wu, L.; Zhang, L.X.; Pan, X.L.; Chen, W.Y.; Zheng, L.P.; Zheng, Y.H. The proto-oncogene c-src is involved in primordial follicle activation through the PI3K, PKC and MAPK signaling pathways. Reprod. Biol. Endocrinol., 2012, 10(1), 58.
[http://dx.doi.org/10.1186/1477-7827-10-58] [PMID: 22905678]
[33]
Lei, J.; Ingbar, D.H. Src kinase integrates PI3K/Akt and MAPK/ERK1/2 pathways in T3-induced Na-K-ATPase activity in adult rat alveolar cells. Am. J. Physiol. Lung Cell. Mol. Physiol., 2011, 301(5), L765-L771.
[http://dx.doi.org/10.1152/ajplung.00151.2011] [PMID: 21840963]
[34]
Li, Y.; Li, P.; Wang, N. Effect of let 7c on the PI3K/Akt/FoxO signaling pathway in hepatocellular carcinoma. Oncol. Lett., 2020, 21(2), 96.
[http://dx.doi.org/10.3892/ol.2020.12357] [PMID: 33376529]
[35]
Asati, V.; Bharti, S.; Mahapatra, D.; Asati, V.; Budhwani, A. Triggering PIK3CA Mutations in PI3K/Akt/mTOR Axis: Exploration of newer inhibitors and rational preventive strategies. Curr. Pharm. Des., 2016, 22(39), 6039-6054.
[http://dx.doi.org/10.2174/1381612822666160614000053] [PMID: 27296758]
[36]
Ding, J.; Ning, B.; Huang, Y.; Zhang, D.; Li, J.; Chen, C.Y.; Huang, C. PI3K/Akt/JNK/c-Jun signaling pathway is a mediator for arsenite-induced cyclin D1 expression and cell growth in human bronchial epithelial cells. Curr. Cancer Drug Targets, 2009, 9(4), 500-509.
[http://dx.doi.org/10.2174/156800909788486740] [PMID: 19519318]
[37]
Thevathasan, J.V.; Tan, E.; Zheng, H.; Lin, Y.C.; Li, Y.; Inoue, T.; Fivaz, M. The small GTPase HRas shapes local PI3K signals through positive feedback and regulates persistent membrane extension in migrating fibroblasts. Mol. Biol. Cell, 2013, 24(14), 2228-2237.
[http://dx.doi.org/10.1091/mbc.e12-12-0905] [PMID: 23676667]
[38]
Zhang, F.L.; Kong, L.; Zhao, A.H.; Ge, W.; Yan, Z.H.; Li, L.; De Felici, M.; Shen, W. Inflammatory cytokines as key players of apoptosis induced by environmental estrogens in the ovary. Environ. Res., 2021, 198, 111225.
[http://dx.doi.org/10.1016/j.envres.2021.111225] [PMID: 33971129]
[39]
O’Brown, Z.K.; Van Nostrand, E.L.; Higgins, J.P.; Kim, S.K. The inflammatory transcription factors NFκB, STAT1 and STAT3 drive age-associated transcriptional changes in the human kidney. PLoS Genet., 2015, 11(12), e1005734.
[http://dx.doi.org/10.1371/journal.pgen.1005734] [PMID: 26678048]
[40]
Bosch, A.; Li, Z.; Bergamaschi, A.; Ellis, H.; Toska, E.; Prat, A.; Tao, J.J.; Spratt, D.E.; Viola-Villegas, N.T.; Castel, P.; Minuesa, G.; Morse, N.; Rodón, J.; Ibrahim, Y.; Cortes, J.; Perez-Garcia, J.; Galvan, P.; Grueso, J.; Guzman, M.; Katzenellenbogen, J.A.; Kharas, M.; Lewis, J.S.; Dickler, M.; Serra, V.; Rosen, N.; Chandarlapaty, S.; Scaltriti, M.; Baselga, J. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci. Transl. Med., 2015, 7(283), 283ra51.
[http://dx.doi.org/10.1126/scitranslmed.aaa4442] [PMID: 25877889]
[41]
Stossi, F.; Madak-Erdoğan, Z.; Katzenellenbogen, B.S. Macrophage-elicited loss of estrogen receptor-α in breast cancer cells via involvement of MAPK and c-Jun at the ESR1 genomic locus. Oncogene, 2012, 31(14), 1825-1834.
[http://dx.doi.org/10.1038/onc.2011.370] [PMID: 21860415]
[42]
Abdelhamed, S.; Ogura, K.; Yokoyama, S.; Saiki, I.; Hayakawa, Y. AKT-STAT3 pathway as a downstream target of EGFR signaling to regulate PD-L1 expression on NSCLC cells. J. Cancer, 2016, 7(12), 1579-1586.
[http://dx.doi.org/10.7150/jca.14713] [PMID: 27698894]
[43]
Furusawa, J.; Funakoshi-Tago, M.; Mashino, T.; Tago, K.; Inoue, H.; Sonoda, Y.; Kasahara, T. Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-κB p65 in LPS signaling pathway. Int. Immunopharmacol., 2009, 9(4), 499-507.
[http://dx.doi.org/10.1016/j.intimp.2009.01.031] [PMID: 19291859]
[44]
Huang, Z.; Jin, G. Licochalcone B induced apoptosis and autophagy in osteosarcoma tumor cells via the inactivation of PI3K/AKT/mTOR pathway. Biol. Pharm. Bull., 2022, 45(6), 730-737.
[http://dx.doi.org/10.1248/bpb.b21-00991] [PMID: 35431285]
[45]
Liu, Y.; Fan, D. Ginsenoside Rg5 induces apoptosis and autophagy via the inhibition of the PI3K/Akt pathway against breast cancer in a mouse model. Food Funct., 2018, 9(11), 5513-5527.
[http://dx.doi.org/10.1039/C8FO01122B] [PMID: 30207362]
[46]
Peng, X.; Jia, C.; Chi, H.; Wang, P.; Fu, H.; Li, Y.; Wang, Q. Efficacy and pharmacological mechanism of Poria cocos-based formulas combined with chemotherapy for ovarian cancer: A integrated systems pharmacology study. Front. Pharmacol., 2022, 13, 788810.
[http://dx.doi.org/10.3389/fphar.2022.788810] [PMID: 35401186]
[47]
Vallet, N.; Boissel, N.; Elefant, E.; Chevillon, F.; Pasquer, H.; Calvo, C.; Dhedin, N.; Poirot, C. Can some anticancer treatments preserve the ovarian reserve? Oncologist, 2021, 26(6), 492-503.
[http://dx.doi.org/10.1002/onco.13675] [PMID: 33458904]
[48]
Shao, N.; Xiao, Y.; Zhang, J.; Zhu, Y.; Wang, S.; Bao, S. Modified sijunzi decoction inhibits epithelial-mesenchymal transition of non-small cell lung cancer by attenuating AKT/GSK3β pathway in vitro and in vivo. Front. Pharmacol., 2022, 12, 821567.
[http://dx.doi.org/10.3389/fphar.2021.821567] [PMID: 35111070]
[49]
Dai, L.; Zhou, W.J.; Wang, M.; Zhou, S.G.; Ji, G. Efficacy and safety of Sijunzi Decoction for chronic fatigue syndrome with spleen deficiency pattern: Study protocol for a randomized, double-blind, placebo-controlled trial. Ann. Transl. Med., 2019, 7(20), 587.
[http://dx.doi.org/10.21037/atm.2019.09.136] [PMID: 31807568]
[50]
Tian, G.; Wu, C.; Li, J.; Liang, B.; Zhang, F.; Fan, X.; Li, Z.; Wang, Y.; Li, Z.; Liu, D.; Lai-Han Leung, E.; Chen, J. Network pharmacology based investigation into the effect and mechanism of Modified Sijunzi decoction against the subtypes of chronic atrophic gastritis. Pharmacol. Res., 2019, 144, 158-166.
[http://dx.doi.org/10.1016/j.phrs.2019.04.012] [PMID: 30991106]
[51]
Lu, Y.; Lin, H.; Zhang, J.; Wei, J.; Sun, J.; Han, L. Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells. BMC Complement. Altern. Med., 2017, 17(1), 35.
[http://dx.doi.org/10.1186/s12906-016-1549-3] [PMID: 28073341]
[52]
Shang, L.; Wang, Y.; Li, J. Mechanism of Sijunzi Decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation. J Ethnopharmacol, 2022, 302(Pt A), 115876.
[53]
Ding, P.; Guo, Y.; Wang, C.; Chen, J.; Guo, C.; Liu, H.; Shi, Q. A network pharmacology approach for uncovering the antitumor effects and potential mechanisms of the Sijunzi decoction for the treatment of gastric cancer. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-11.
[http://dx.doi.org/10.1155/2022/9364313] [PMID: 35463069]
[54]
Shin, E.Y.; Kim, D.S.; Lee, M.J.; Lee, A.R.; Shim, S.H.; Baek, S.W.; Han, D.K.; Lee, D.R. Prevention of chemotherapy-induced premature ovarian insufficiency in mice by scaffold-based local delivery of human embryonic stem cell-derived mesenchymal progenitor cells. Stem Cell Res. Ther., 2021, 12(1), 431.
[http://dx.doi.org/10.1186/s13287-021-02479-3] [PMID: 34332643]
[55]
Chen, J.M.; Yang, T.T.; Cheng, T.S.; Hsiao, T.F.; Chang, P.M.H.; Leu, J.Y.; Wang, F.S.; Hsu, S.L.; Huang, C.Y.F.; Lai, J.M. Modified Sijunzi decoction can allevia te cisplatin-induced toxicity and prolong the survival time of cachectic mice by recovering muscle atrophy. J. Ethnopharmacol., 2019, 233, 47-55.
[http://dx.doi.org/10.1016/j.jep.2018.12.035] [PMID: 30590199]
[56]
Guan, Z.; Wu, J.; Wang, C.; Zhang, F.; Wang, Y.; Wang, M.; Zhao, M.; Zhao, C. Investigation of the preventive effect of Sijunzi decoction on mitomycin C-induced immunotoxicity in rats by 1 H NMR and MS-based untargeted metabolomic analysis. J. Ethnopharmacol., 2018, 210, 179-191.
[http://dx.doi.org/10.1016/j.jep.2017.08.021] [PMID: 28866044]
[57]
Sun, L.; Mao, J.J.; Yan, Y.; Xu, Y.; Yang, Y. Patient Reported Traditional Chinese Medicine Spleen Deficiency Syndrome (TCM-SDS) scale for colorectal cancer: Development and validation in China. Integr. Cancer Ther., 2021, 20.
[http://dx.doi.org/10.1177/15347354211020105] [PMID: 34116615]
[58]
Wang, Y.; Teng, X.; Liu, J. Research progress on the effect of traditional chinese medicine on signal pathway related to premature ovarian insufficiency. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-13.
[http://dx.doi.org/10.1155/2022/7012978] [PMID: 36159578]
[59]
Dou, X.; Jin, X.; Chen, X.; Zhou, Q.; Chen, H.; Wen, M.; Chen, W. Bu-Shen-Ning-Xin decoction allevia tes premature ovarian insufficiency (POI) by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway. Gynecol. Endocrinol., 2022, 38(9), 754-764.
[http://dx.doi.org/10.1080/09513590.2022.2112941] [PMID: 35989579]
[60]
Shen, J.Z.; Wu, G.; Guo, S. Amino acids in autophagy: Regulation and function. Adv. Exp. Med. Biol., 2021, 1332, 51-66.
[http://dx.doi.org/10.1007/978-3-030-74180-8_4] [PMID: 34251638]
[61]
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(D1), D789-D798.
[http://dx.doi.org/10.1093/nar/gku1205] [PMID: 25428349]
[62]
Safran, M.; Dalah, I.; Alexander, J.; Rosen, N.; Iny Stein, T.; Shmoish, M.; Nativ, N.; Bahir, I.; Doniger, T.; Krug, H.; Sirota-Madi, A.; Olender, T.; Golan, Y.; Stelzer, G.; Harel, A.; Lancet, D. GeneCards Version 3: The human gene integrator. Database, 2010, 2010(0), baq020.
[http://dx.doi.org/10.1093/database/baq020] [PMID: 20689021]
[63]
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]

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