دورية أكاديمية
Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression.
العنوان: | Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression. |
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المؤلفون: | Zhou N; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Lv W; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Chen L; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Chen K; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., He Q; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Xie G; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Ma J; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China., Cao Y; Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 199 South Jiefang Road, Xuzhou, 221004, China., Zhang B; Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 199 South Jiefang Road, Xuzhou, 221004, China. bettyzhang10@163.com., Zhou X; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China. zxy851107@xzhmu.edu.cn. |
المصدر: | Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2024 Aug; Vol. 31 (8), pp. 2234-2245. Date of Electronic Publication: 2024 Mar 18. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 101291249 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1933-7205 (Electronic) Linking ISSN: 19337191 NLM ISO Abbreviation: Reprod Sci Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2020- : [New York] : Springer Original Publication: Thousand Oaks, Calif. : Sage |
مواضيع طبية MeSH: | Polycystic Ovary Syndrome*/metabolism , Polycystic Ovary Syndrome*/drug therapy , Polycystic Ovary Syndrome*/chemically induced , Polycystic Ovary Syndrome*/pathology , Receptors, Aryl Hydrocarbon*/metabolism , Estrogens*/pharmacology , Estrogens*/metabolism , Cytochrome P-450 CYP1A2*/metabolism, Female ; Animals ; Humans ; Mice ; Cytochrome P-450 CYP1A1/metabolism ; Ovary/drug effects ; Ovary/metabolism ; Ovary/pathology ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Disease Models, Animal ; Adult |
مستخلص: | Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS. (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.) |
References: | Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol. 2014;10(10):624–36. https://doi.org/10.1038/nrendo.2014.102. (PMID: 10.1038/nrendo.2014.10225022814) Azziz R, Carmina E, Chen ZJ, et al. Polycystic ovary syndrome. Nat Rev Dis Prim. 2016;2:16057. https://doi.org/10.1038/nrdp.2016.57. (PMID: 10.1038/nrdp.2016.5727510637) Kumariya S, Ubba V, Jha RK, Gayen JR. Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective. Autophagy. 2021;17(10):2706–32. https://doi.org/10.1080/15548627.2021.1938914. (PMID: 10.1080/15548627.2021.1938914341611858526011) MohanKumar SMJ, Balasubramanian P, Subramanian M, MohanKumar PS. Chronic estradiol exposure - harmful effects on behavior, cardiovascular and reproductive functions. Reproduction. 2018;156(5):R169–86. https://doi.org/10.1530/REP-18-0116. (PMID: 10.1530/REP-18-011630328341) Med ASR. The clinical relevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2012;98(5):1112–7. https://doi.org/10.1016/j.fertnstert.2012.06.050. (PMID: 10.1016/j.fertnstert.2012.06.050) De Souza MJ, Miller BE, Loucks AB, et al. High frequency of luteal phase deficiency and anovulation in recreational women runners: Blunted elevation in follicle-stimulating hormone observed during luteal-follicular transition. J Clin Endocrinol Metab. 1998;83(12):4220–32. https://doi.org/10.1210/jc.83.12.4220. (PMID: 10.1210/jc.83.12.42209851755) Qi J, Wang Y, Zhu QL, et al. Novel role of CXCL14 in modulating STAR expression in luteinized granulosa cells: implication for progesterone synthesis in PCOS patients. Transl Res. 2021;230:55–67. https://doi.org/10.1016/j.trsl.2020.10.009. (PMID: 10.1016/j.trsl.2020.10.00933129993) Harlow CR, Shaw HJ, Hillier SG, Hodges JK. Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity. Endocrinology. 1988;122(6):2780–7. https://doi.org/10.1210/endo-122-6-2780. (PMID: 10.1210/endo-122-6-27803131124) Bertoldo MJ, Caldwell ASL, Riepsamen AH, et al. A Hyperandrogenic Environment Causes Intrinsic Defects That Are Detrimental to Follicular Dynamics in a PCOS Mouse Model. Endocrinology. 2019;160(3):699–715. https://doi.org/10.1210/en.2018-00966. (PMID: 10.1210/en.2018-0096630657917) Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016;37(5):467–520. https://doi.org/10.1210/er.2015-1104. (PMID: 10.1210/er.2015-1104274592305045492) Wang L, Xiao Y, Tian T, et al. Digenic variants of planar cell polarity genes in human neural tube defect patients (vol 124, pg 94, 2018). Mol Genet Metab. 2021;132(3):211. https://doi.org/10.1016/j.ymgme.2021.01.010. (PMID: 10.1016/j.ymgme.2021.01.01033582009) Simpson ER, Clyne C, Rubin G, et al. Aromatase–a brief overview. Annu Rev Physiol. 2002;64:93–127. https://doi.org/10.1146/annurev.physiol.64.081601.142703. (PMID: 10.1146/annurev.physiol.64.081601.14270311826265) Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril. 2004;81(2):290–6. https://doi.org/10.1016/j.fertnstert.2003.09.029. (PMID: 10.1016/j.fertnstert.2003.09.02914967362) Geffner ME. Aromatase inhibitors to augment height: continued caution and study required. J Clin Res Pediatr Endocrinol. 2009;1(6):256–61. https://doi.org/10.4274/jcrpe.v1i6.256. (PMID: 10.4274/jcrpe.v1i6.25621274305) Arlt W. Dehydroepiandrosterone replacement therapy. Semin Reprod Med. 2004;22(4):379–88. https://doi.org/10.1055/s-2004-861554. (PMID: 10.1055/s-2004-86155415635505) Lambard S, Galeraud-Denis I, Bouraima H, et al. Expression of aromatase in human ejaculated spermatozoa: a putative marker of motility. Mol Hum Reprod. 2003;9(3):117–24. https://doi.org/10.1093/molehr/gag020. (PMID: 10.1093/molehr/gag02012606587) Tsuchiya Y, Nakajima M, Yokoi T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005;227(2):115–24. https://doi.org/10.1016/j.canlet.2004.10.007. (PMID: 10.1016/j.canlet.2004.10.00716112414) Okino ST, Pookot D, Basak S, Dahiya R. Toxic and chemopreventive ligands preferentially activate distinct aryl hydrocarbon receptor pathways: implications for cancer prevention. Cancer Prev Res (Phila). 2009;2(3):251–6. https://doi.org/10.1158/1940-6207.CAPR-08-0146. (PMID: 10.1158/1940-6207.CAPR-08-014619223575) Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. Bmc Complem Altern M. 2014;14:511. https://doi.org/10.1186/1472-6882-14-511. (PMID: 10.1186/1472-6882-14-511) Raja-Khan N, Stener-Victorin E, Wu X, Legro RS. The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. Am J Physiol Endocrinol Metab. 2011;301(1):E1–10. https://doi.org/10.1152/ajpendo.00667.2010. (PMID: 10.1152/ajpendo.00667.2010214870754459923) Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Updat. 1997;3(4):359–65. https://doi.org/10.1093/humupd/3.4.359. (PMID: 10.1093/humupd/3.4.359) Mulligan K, Yang Y, Wininger DA, et al. Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio. AIDS. 2007;21(1):47–57. https://doi.org/10.1097/QAD.0b013e328011220e. (PMID: 10.1097/QAD.0b013e328011220e17148967) Maged AM, Elsawah H, Abdelhafez A, Bakry A, Al MW. The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome. Gynecol Endocrinol. 2015;31(8):635–8. https://doi.org/10.3109/09513590.2015.1037269. (PMID: 10.3109/09513590.2015.103726926291797) Ding J, Xu Y, Ma XP, et al. Estrogenic effect of the extract of Renshen (Radix Ginseng) on reproductive tissues in immature mice. J Tradit Chin Med. 2015;35(4):460–7. (PMID: 10.1016/S0254-6272(15)30125-426427118) Cho J, Park W, Lee S, Ahn W, Lee Y. Ginsenoside-Rb1 from Panax ginseng C.A. Meyer activates estrogen receptor-alpha and -beta, independent of ligand binding. J Clin Endocrinol Metab. 2004;89(7):3510–5. https://doi.org/10.1210/jc.2003-031823. (PMID: 10.1210/jc.2003-03182315240639) Wu JY, Pan ZF, Wang ZQ, et al. Ginsenoside Rg1 protection against beta-amyloid peptide-induced neuronal apoptosis via estrogen receptor alpha and glucocorticoid receptor-dependent anti-protein nitration pathway. Neuropharmacology. 2012;63(3):349–61. https://doi.org/10.1016/j.neuropharm.2012.04.005. (PMID: 10.1016/j.neuropharm.2012.04.00522534050) Choi JH, Jang M, Kim EJ, et al. Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities. J Ginseng Res. 2020;44(6):790–8. https://doi.org/10.1016/j.jgr.2019.08.007. (PMID: 10.1016/j.jgr.2019.08.00733192122) Yoshikawa M, Murakami T, Ikebata A, et al. Bioactive saponins and glycosides. 10. On the constituents of Zizyphi Spinosi Semen, the seeds of Zizyphus jujuba Mill, var spinosa Hu. 1. Structures and histamine release-inhibitory effects of jujubosides A(1) and C and acetyljujuboside B. Chem Pharm Bull. 1997;45(7):1186–92. (PMID: 10.1248/cpb.45.1186) Li HT, Li JN, Zhang T, Xie XY, Gong JY. Antidepressant effect of Jujuboside A on corticosterone-induced depression in mice. Biochem Bioph Res Co. 2022;620:56–62. https://doi.org/10.1016/j.bbrc.2022.06.076 . (PMID: 10.1016/j.bbrc.2022.06.076) Di Emidio G, Rea F, Placidi M, et al. Regulatory functions of L-Carnitine, acetyl, and propionyl L-Carnitine in a PCOS mouse model: focus on antioxidant/antiglycative molecular pathways in the ovarian microenvironment. Antioxidants (Basel). 2020;9(9). https://doi.org/10.3390/antiox9090867. Zhou X, Zheng Z, Xu C, et al. Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer. J Pharm Sci. 2017;106(8):2152–62. https://doi.org/10.1016/j.xphs.2017.04.073. (PMID: 10.1016/j.xphs.2017.04.07328479355) Hao Z, Xu J, Zhao H, et al. The inhibition of tamoxifen on UGT2B gene expression and enzyme activity in rat liver contribute to the estrogen homeostasis dysregulation. BMC Pharmacol Toxicol. 2022;23(1):33. https://doi.org/10.1186/s40360-022-00574-6. (PMID: 10.1186/s40360-022-00574-6356420279158366) Sakurai S, Shimizu T, Ohto U. The crystal structure of the AhRR-ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription. J Biol Chem. 2017;292(43):17609–16. https://doi.org/10.1074/jbc.M117.812974. (PMID: 10.1074/jbc.M117.812974289041765663866) Rodgers RJ, Suturina L, Lizneva D, et al. Is polycystic ovary syndrome a 20th Century phenomenon? Med Hypotheses. 2019;124:31–4. https://doi.org/10.1016/j.mehy.2019.01.019. (PMID: 10.1016/j.mehy.2019.01.01930798911) Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020;502:214–21. https://doi.org/10.1016/j.cca.2019.11.003. (PMID: 10.1016/j.cca.2019.11.00331733195) Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol. 2018;182:27–36. https://doi.org/10.1016/j.jsbmb.2018.04.008. (PMID: 10.1016/j.jsbmb.2018.04.00829678491) Jazani AM, Azgomi HND, Azgomi AND, Azgomi RND. A comprehensive review of clinical studies with herbal medicine on polycystic ovary syndrome (PCOS). Daru. 2019;27(2):863–77. https://doi.org/10.1007/s40199-019-00312-0. (PMID: 10.1007/s40199-019-00312-0) Krishnan A, Muthusami S. Hormonal alterations in PCOS and its influence on bone metabolism. J Endocrinol. 2017;232(2):R99–113. https://doi.org/10.1530/Joe-16-0405. (PMID: 10.1530/Joe-16-040527895088) Balthazart J, Cornil CA, Charlier TD, Taziaux M, Ball GF. Estradiol, a Key Endocrine Signal in the Sexual Differentiation and Activation of Reproductive Behavior in Quail. J Exp Zool Part A. 2009;311a(5):323–45. https://doi.org/10.1002/jez.464. (PMID: 10.1002/jez.464) Reinen J, Vermeulen NP. Biotransformation of endocrine disrupting compounds by selected phase I and phase II enzymes–formation of estrogenic and chemically reactive metabolites by cytochromes P450 and sulfotransferases. Curr Med Chem. 2015;22(4):500–27. https://doi.org/10.2174/0929867321666140916123022. (PMID: 10.2174/092986732166614091612302225245506) Kaderbhai MA, Kelly SL, Kaderbhai NN. Towards engineered topogenesis of cytochrome b(5) and P450 for in vivo transformation of xenobiotics. Biochem Soc T. 2006;34:1231–5. https://doi.org/10.1042/Bst0341231. (PMID: 10.1042/Bst0341231) Cribb AE, Knight MJ, Dryer D, et al. Role of polymorphic human cytochrome P450 enzymes in estrone oxidation. Cancer Epidem Biomar. 2006;15(3):551–8. https://doi.org/10.1158/1055-9965.Epi-05-0801. (PMID: 10.1158/1055-9965.Epi-05-0801) Daujat M, Clair P, Astier C, et al. Induction, regulation and messenger half-life of cytochromes P450 IA1, IA2 and IIIA6 in primary cultures of rabbit hepatocytes. CYP 1A1, 1A2 and 3A6 chromosome location in the rabbit and evidence that post-transcriptional control of gene IA2 does not involve mRNA stabilization. Eur J Biochem. 1991;200(2):501–10. https://doi.org/10.1111/j.1432-1033.1991.tb16211.x. (PMID: 10.1111/j.1432-1033.1991.tb16211.x1889414) Tompkins LM, Wallace AD. Mechanisms of cytochrome P450 induction. J Biochem Mol Toxic. 2007;21(4):176–81. https://doi.org/10.1002/jbt.20180. (PMID: 10.1002/jbt.20180) Vogel CFA, Van Winkle LS, Esser C, Haarmann-Stemmann T. The aryl hydrocarbon receptor as a target of environmental stressors - Implications for pollution mediated stress and inflammatory responses. Redox Biol. 2020;34:101530. https://doi.org/10.1016/j.redox.2020.101530. (PMID: 10.1016/j.redox.2020.101530323546407327980) Couse JF, Yates MM, Deroo BJ, Korach KS. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Endocrinology. 2005;146(8):3247–62. https://doi.org/10.1210/en.2005-0213. (PMID: 10.1210/en.2005-021315831568) Horling K, Santos AN, Fischer B. The AhR is constitutively activated and affects granulosa cell features in the human cell line KGN. Mol Hum Reprod. 2011;17(2):104–14. https://doi.org/10.1093/molehr/gaq074. (PMID: 10.1093/molehr/gaq07420823264) Mottershead DG, Pulkki MM, Muggalla P, et al. Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells. Mol Cell Endocrinol. 2008;283(1–2):58–67. https://doi.org/10.1016/j.mce.2007.11.007. (PMID: 10.1016/j.mce.2007.11.00718162287) |
معلومات مُعتمدة: | KC23255 Science and Technology Foundation of Xuzhou; 18KA350002 Natural Science Foundation of the Jiangsu Higher Education Institutions of China; H2017079 Provincial Commission of Health and Family Planning in Jiangsu Province; BE2019636 Science and Technology Planning Project of Jiangsu Province; 82173883 Natural Science Foundation of China; MS2023175 the administration of Traditional Chinese Medicine in Jiangsu Province |
فهرسة مساهمة: | Keywords: Aryl hydrocarbon receptor; CYP1A2; Estrogen metabolism; Hormone homeostasis; Jujuboside A; Polycystic ovary syndrome |
المشرفين على المادة: | 0 (Receptors, Aryl Hydrocarbon) 0 (Estrogens) EC 1.14.14.1 (Cytochrome P-450 CYP1A2) EC 1.14.14.1 (Cytochrome P-450 CYP1A1) 0 (AHR protein, human) 0 (Basic Helix-Loop-Helix Transcription Factors) EC 1.14.14.1 (CYP1A2 protein, human) |
تواريخ الأحداث: | Date Created: 20240319 Date Completed: 20240730 Latest Revision: 20240730 |
رمز التحديث: | 20240730 |
DOI: | 10.1007/s43032-024-01511-0 |
PMID: | 38499949 |
قاعدة البيانات: | MEDLINE |
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