Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Ginsenoside Rg1 Attenuates Premature Ovarian Failure of D-gal Induced POF Mice Through Downregulating p16INK4a and Upregulating SIRT1 Expression

Author(s): Xiao-Hu Liu, Shi-Zhong Cai, Yue Zhou*, Ya-Ping Wang*, Yan-Jun Han, Cui-Li Wang and Wen Zhou

Volume 22, Issue 3, 2022

Published on: 12 January, 2022

Page: [318 - 327] Pages: 10

DOI: 10.2174/1871523020666210830164152

Price: $65

Abstract

Background: Premature ovarian failure (POF) refers to pathological amenorrhea before 40 years.

Objective: To explore the regulatory effect of Rg1 on POF and clarify associated mechanisms.

Materials and Methods: POF mice were induced by injecting with D-galactose (D-gal, 200 mg/kg/- day). Mice were divided into phosphate buffered saline (PBS), D-gal (POF mice), D-gal/Rg1 group (POF mice administrating D-gal/Rg1). Weight growth rate and ovarian weight coefficient were measured. Serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), catalase (CAT) levels were examined using ELISA. The status of follicle and corpus luteum was determined using hematoxylin-eosin (HE) staining. P16INK4a and silent- mating type information regulation-2 homolog-1 (SIRT1) were determined using western blotting and RT-PCR.

Results: Weight growth rate and ovarian weight coefficient of mice in D-gal group were significantly decreased than PBS group (p<0.05). Serum E2, LH, SOD, CAT levels were significantly decreased, FSH levels were remarkably increased in D-gal group than PBS group (p<0.05). Rg1 (D-- gal/Rg1 group) significantly increased weight growth rate and ovarian weight coefficient, enhanced E2, LH, SOD, CAT levels and decreased FSH levels than D-gal group (p<0.05). HE staining demonstrated normal follicle morphology/structure of mice in PBS group and decreased the number of follicles, obvious vacuolation of corpus luteum and increased atretic follicles of mice in D-gal group. Compared with D-gal group, the number of follicles was increased, luteal follicles were decreased in mice in D-gal/Rg1 group (p<0.05). Rg1 significantly (D-gal/Rg1) downregulated p16INK4a and upregulated SIRT1 expression in ovarian tissues of mice compared to the D-gal group (p<0.05).

Conclusion: Rg1 could delay premature ovarian failure in D-gal induced POF mouse model through downregulating p16INK4a and upregulating SIRT1 expression.

Keywords: Ginsenoside Rg1, premature ovarian failure, SIRT1, D-gal, aging, chinese medicine.

« Previous Next »
Graphical Abstract

[1]
Kawamura, K.; Kawamura, N.; Hsueh, A.J. Activation of dormant follicles: A new treatment for premature ovarian failure? Curr. Opin. Obstet. Gynecol., 2016, 28(3), 217-222.
[http://dx.doi.org/10.1097/GCO.0000000000000268] [PMID: 27022685]
[2]
Schirinzi, A.; Cazzolla, A.P.; Mascolo, E.; Palmieri, G.; Pesce, F.; Gesualdo, L.; Santacroce, L.; Ballini, A.; Lovero, R.; Di Serio, F. Determination of the upper reference limit of human epididymis secretory protein 4 (HE4) in healthy male individucals and correlation with renal and fertility markers. Endocr. Metab. Immune Disord. Drug Targets, 2021, 21(5), 912-918.
[http://dx.doi.org/10.2174/1871530320666200807121050] [PMID: 32767951]
[3]
Laml, T.; Schulz-Lobmeyr, I.; Obruca, A.; Huber, J.C.; Hartmann, B.W. Premature ovarian failure: Etiology and prospects. Gynecol. Endocrinol., 2000, 14(4), 292-302.
[http://dx.doi.org/10.3109/09513590009167696] [PMID: 11075301]
[4]
Cui, Q.; Ji, Z.Q.; Feng, J. Treatment of premature ovarian failure patients of Shen Yang deficiency syndrome by warming Shen, enhancing Yang, invigorating qi, and nourishing blood method combined artificial cycle therapy: A clinical observation. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2013, 33(12), 1642-1644.
[PMID: 24517061]
[5]
Magyar, Z.; Berkes, E.; Csapo, Z.; Papp, Z. Effect of hormone replacement therapy on postmenopausal endometrial bleeding. Pathol. Oncol. Res., 2007, 13(4), 351-359.
[http://dx.doi.org/10.1007/BF02940316] [PMID: 18158572]
[6]
Zhao, B.; Lv, C.; Lu, J. Natural occurring polysaccharides from Panax ginseng C. A. Meyer: A review of isolation, structures, and bioactivities. Int. J. Biol. Macromol., 2019, 133(1), 324-336.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.03.229] [PMID: 30943421]
[7]
Yan, X.; Zhang, W.; Kong, F.; Li, Q.; Shan, W.; Zhang, C.; Han, T.; Che, Y.; Zhang, Y. Ginsenoside Rg3 reduces epithelial-mesenchymal transition induced by transforming growth facto-beta 1 by inacivation of AKT in HMrSV5 peritoneal mesothelial cells. Med. Sci. Monit., 2019, 25(1), 6972-6979.
[http://dx.doi.org/10.12659/MSM.915991] [PMID: 31527568]
[8]
Guan, S.; Yu, P.; Cao, J.; Xi, X.; Zhang, Q.; Zhu, C.; Hu, H.; Gong, X.; Fan, H. Ginsenoside Rg1 protects against cigarette smoke-induced airway remodeling by suppressing the TGF-β1/Smad3 signaling pathway. Am. J. Transl. Res., 2020, 12(2), 493-506.
[PMID: 32194898]
[9]
Wang, Z.L.; Chen, L.B.; Qiu, Z.; Chen, X.B.; Liu, Y.; Li, J.; Wang, L.; Wang, Y.P. Ginsenoside Rg1 ameliorates testicular senescence changes in D‑gal‑induced aging mice via anti‑inflammatory and antioxidative mechanisms. Mol. Med. Rep., 2018, 17(5), 6269-6276.
[PMID: 29512726]
[10]
Jeong, H.J.; So, H.K.; Jo, A.; Kim, H.B.; Lee, S.J.; Bae, G.U.; Kang, J.S. Ginsenoside Rg1 augments oxidative metabolism and anabolic response of skeletal muscle in mice. J. Ginseng Res., 2019, 43(3), 475-481.
[http://dx.doi.org/10.1016/j.jgr.2018.04.005] [PMID: 31308819]
[11]
He, L.; Ling, L.; Wei, T.; Wang, Y.; Xiong, Z. Ginsenoside Rg1 improves fertility and reduces ovarian pathological damages in premature ovarian failure model of mice. Exp. Biol. Med. (Maywood), 2017, 242(7), 683-691.
[http://dx.doi.org/10.1177/1535370217693323] [PMID: 28178855]
[12]
Zhou, Y.; Yang, B.; Yao, X.; Wang, Y. [Experimental study of relationship between effect of ginsenoside Rg1 to delay hematopoietic stem cell senescence and expression of p16(INK4a)]. Zhongguo Zhongyao Zazhi, 2011, 36(5), 608-613.
[PMID: 21657082]
[13]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[14]
Lin, J.; Nie, X.; Xiong, Y.; Gong, Z.; Chen, J.; Chen, C.; Huang, Y.; Liu, T. Fisetin regulates gut microbiota to decrease CCR9+/CXCR3+/CD4+ T-lymphocyte count and IL-12 secretion to alleviate premature ovarian failure in mice. Am. J. Transl. Res., 2020, 12(1), 203-247.
[PMID: 32051749]
[15]
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]
[16]
Machura, P.; Grymowicz, M.; Rudnicka, E.; Pięta, W.; Calik-Ksepka, A.; Skórska, J.; Smolarczyk, R. Premature ovarian insufficiency - hormone replacement therapy and management of long-term consequences. Przegl. Menopauz., 2018, 17(3), 135-138.
[http://dx.doi.org/10.5114/pm.2018.78559] [PMID: 30357030]
[17]
Agarwal, S.; Alzahrani, F.A.; Ahmed, A. Hormone replacement therapy: Would it be possible to replicate a functional ovary? Int. J. Mol. Sci., 2018, 19(10), 3160.
[http://dx.doi.org/10.3390/ijms19103160] [PMID: 30322209]
[18]
Melnick, A.P.; Rosenwaks, Z. Oocyte donation: Insights gleaned and future challenges. Fertil. Steril., 2018, 110(6), 988-993.
[http://dx.doi.org/10.1016/j.fertnstert.2018.09.021] [PMID: 30396566]
[19]
Liu, J.; Chen, D.; Wang, Z.; Chen, C.; Ning, D.; Zhao, S. Protective effect of walnut on d-galactose-induced aging mouse model. Food Sci. Nutr., 2019, 7(3), 969-976.
[http://dx.doi.org/10.1002/fsn3.907] [PMID: 30918639]
[20]
Zhou, Y.; Song, J.; Wang, Y.P.; Zhang, A.M.; Tan, C.Y.; Liu, Y.H.; Zhang, Z.P.; Wang, Y.; Ma, K.T.; Li, L.; Si, J.Q. Age‑associated variation in the expression and function of TMEM16A calcium‑activated chloride channels in the cochlear stria vascularis of guinea pigs. Mol. Med. Rep., 2019, 20(2), 1593-1604.
[http://dx.doi.org/10.3892/mmr.2019.10423] [PMID: 31257512]
[21]
Berry, G.T. Galactosemia and amenorrhea in the adolescent. Ann. N. Y. Acad. Sci., 2008, 1135(1), 112-117.
[http://dx.doi.org/10.1196/annals.1429.038] [PMID: 18574215]
[22]
Sozen, B.; Ozekinci, M.; Erman, M.; Gunduz, T.; Demir, N.; Akouri, R. Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model. J. Assist. Reprod. Genet., 2019, 36(10), 2181-2189.
[http://dx.doi.org/10.1007/s10815-019-01560-4] [PMID: 31422495]
[23]
Park, H.J.; Choe, S.; Park, N.C. Effects of Korean red ginseng on semen parameters in male infertility patients: A randomized, placebo-controlled, double-blind clinical study. Chin. J. Integr. Med., 2016, 22(7), 490-495.
[http://dx.doi.org/10.1007/s11655-015-2139-9] [PMID: 25967606]
[24]
Wei, C.; Jia, J.; Liang, P.; Guan, Y. Ginsenoside Rg1 attenuates beta-amyloid-induced apoptosis in mutant PS1 M146L cells. Neurosci. Lett., 2008, 443(3), 145-149.
[http://dx.doi.org/10.1016/j.neulet.2008.07.089] [PMID: 18694806]
[25]
Xiang, Y.; Wang, S.H.; Wang, L.; Wang, Z.L.; Yao, H.; Chen, L.B.; Wang, Y.P. Effects of ginsenodise Rg1 regulating Wnt/beta-catenin signaling on neural stem cells to delay brain senescence. Stem Cells Int., 2019, 2019, 5010184.
[http://dx.doi.org/10.1155/2019/5010184] [PMID: 31885611]
[26]
Xiao, M.H.; Xia, J.Y.; Wang, Z.L.; Hu, W.X.; Fan, Y.L.; Jia, D.Y.; Li, J.; Jing, P.W.; Wang, L.; Wang, Y.P. Ginsenoside Rg1 attenuates liver injury induced by D-galactose in mice. Exp. Ther. Med., 2018, 16(5), 4100-4106.
[http://dx.doi.org/10.3892/etm.2018.6727] [PMID: 30402153]
[27]
Cai, S.Z.; Zhou, Y.; Liu, J.; Li, C.P.; Jia, D.Y.; Zhang, M.S.; Wang, Y.P. Alleviation of ginsenoside Rg1 on hematopoietic homeostasis defects caused by lead-acetate. Biomed. Pharmacother., 2018, 97(1), 1204-1211.
[http://dx.doi.org/10.1016/j.biopha.2017.10.148] [PMID: 29145145]
[28]
Tang, Y.L.; Zhou, Y.; Wang, Y.P.; Wang, J.W.; Ding, J.C. SIRT6/NF-κB signaling axis in ginsenoside Rg1-delayed hematopoietic stem/progenitor cell senescence. Int. J. Clin. Exp. Pathol., 2015, 8(5), 5591-5596.
[PMID: 26191269]
[29]
Liu, J.; Cai, S.Z.; Zhou, Y.; Zhang, X.P.; Liu, D.F.; Jiang, R.; Wang, Y.P. Senescence as a consequence of ginsenoside rg1 response on k562 human leukemia cell line. Asian Pac. J. Cancer Prev., 2012, 13(12), 6191-6196.
[http://dx.doi.org/10.7314/APJCP.2012.13.12.6191] [PMID: 23464429]
[30]
Prestoz, L.L.; Couto, A.S.; Shin, Y.S.; Petry, K.G. Altered follicle stimulating hormone isoforms in female galactosaemia patients. Eur. J. Pediatr., 1997, 156(2), 116-120.
[http://dx.doi.org/10.1007/s004310050568] [PMID: 9039515]
[31]
Menezo, Y.J.; Lescaille, M.; Nicollet, B.; Servy, E.J. Pregnancy and delivery after stimulation with rFSH of a galatosemia patient suffering hypergonadotropic hypogonadism: Case report. J. Assist. Reprod. Genet., 2004, 21(3), 89-90.
[http://dx.doi.org/10.1023/B:JARG.0000027020.28592.7b] [PMID: 15202737]
[32]
Zhang, W.; Huang, Q.; Zeng, Z.; Wu, J.; Zhang, Y.; Chen, Z. Sirt1 inhibits oxidative stress in vascular endothelial cells. Oxid. Med. Cell. Longev., 2017, 2017, 7543973.
[http://dx.doi.org/10.1155/2017/7543973] [PMID: 28546854]
[33]
Han, Y.; Luo, H.; Wang, H.; Cai, J.; Zhang, Y. SIRT1 induces resistance to apoptosis in human granulosa cells by activating the ERK pathway and inhibiting NF-κB signaling with anti-inflammatory functions. Apoptosis, 2017, 22(10), 1260-1272.
[http://dx.doi.org/10.1007/s10495-017-1386-y] [PMID: 28755171]
[34]
Seifert, E.L.; Caron, A.Z.; Morin, K.; Coulombe, J.; He, X.H.; Jardine, K.; Dewar-Darch, D.; Boekelheide, K.; Harper, M.E.; McBurney, M.W. SirT1 catalytic activity is required for male fertility and metabolic homeostasis in mice. FASEB J., 2012, 26(2), 555-566.
[http://dx.doi.org/10.1096/fj.11-193979] [PMID: 22006156]
[35]
Chang, H.C.; Guarente, L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol. Metab., 2014, 25(3), 138-145.
[http://dx.doi.org/10.1016/j.tem.2013.12.001] [PMID: 24388149]

Rights & Permissions Print Cite
Article Metrics
25
1
© 2024 Bentham Science Publishers | Privacy Policy