Please wait a minute...
Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (4): 530-536    DOI: 10.31083/j.ceog.2020.04.5428
Original Research Previous articles | Next articles
The effect of rhodiola rosea root extract on stress-induced ovarian damage, infertility and reproductive disorders in female rats
B.G. Kadioglu1, B. Gundogdu2, N. Kurt3, A. Ozbek Bilgin4, H. Suleyman4, *(), Z. Suleyman5
1Department of Obstetrics and Gynecology, Regional Training Research Hospital, Health Sciences University, Erzurum, Turkey
2Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
3Department of Biochemistry, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
4Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
5Department of Nursing, Faculty of Health Sciences, Erzincan Binali Yildirim University, Erzincan, Turkey
Download:  PDF(622KB)  ( 368 ) Full text   ( 13 )
Export:  BibTeX | EndNote (RIS)      
Abstract  

Purpose: The aim of the study was to examine the possible effect of Rhodiola rosea root extract (RRE) on ovarian damage, infertility (IF), delay in conception (DC), decrease in the number of offspring (NO) in female rats that have been stressed with compulsory immobilization method (CIM) and on retardation of intrauterine physical development (IPD) in offspring. Materials and methods: Female Albino Wistar rats were divided like: healthy (HG), stress-induced control (SC), and stress + 50 mg/kg RRE (S + REG) groups including sixteen rats in each group. Six rats from each group were killed for conducting biochemical and histopathological examinations in ovarian tissues and others were observed for IF, DC, NO, and IPD. Results: It was found that RRE significantly prevented the increase in oxidative parameters and proinflammatory cytokine levels in ovarian tissue of animals stressed with CIM. RRE suppressed the increase in IF rate and DC whereas caused a decrease in NO and in IPD retardation. Conclusion: These results suggested RRE may have beneficial effects in the treatment of stress induced reproductive dysfunction. Content: The effect of RRE on oxidative and inflammatory changes in ovarian tissue and reproductive changes of animals exposed to stress with compulsory immobilization method.

Key words:  Ovarian damage      Stress      Infertility      Rhodiola rosea root     
Submitted:  14 November 2019      Accepted:  22 May 2020      Published:  15 August 2020     
*Corresponding Author(s):  H. Suleyman     E-mail:  halis.suleyman@gmail.com

Cite this article: 

B.G. Kadioglu, B. Gundogdu, N. Kurt, A. Ozbek Bilgin, H. Suleyman, Z. Suleyman. The effect of rhodiola rosea root extract on stress-induced ovarian damage, infertility and reproductive disorders in female rats. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 530-536.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.04.5428     OR     https://ceog.imrpress.com/EN/Y2020/V47/I4/530

Figure 1.  — MDA and tGSH levels in ovarian tissues of experimental groups. * p < 0.001, according to HG and S + REG group, ** p > 0.05, according to HG group.
HG: healthy group, SC: stress control group, and S+REG: stress + 50 mg/kg Rhodiola rosea root extract group. MDA: Malondialdehyde, tGSH: Total Glutathione, p according to one-way analysis of variance test followed by post-hoc Tukey test.


Figure 2.  — Oxidant/antioxidant balance in the ovarian tissues of experimental groups. * p < 0.001, according to HG and S + REG group, ** p > 0.05, according to HG group.
HG: healthy group, SC: stress control group, and S + REG: stress + 50 mg/kg Rhodiola rosea root extract group. TAS: Total Anti-oxidant Status and TOS: Total Oxidant Status, p according to one-way analysis of variance test followed by post-hoc Tukey test.


Figure 3.  — NF-κB levels in in the ovarian tissues of experimental groups. * p <0.001, according to HG and S + REG group.
HG: healthy group, SC: stress control group, and S + REG: stress + 50 mg/kg Rhodiola rosea root extract group. NF-κB: Nuclear Factor- Kappa B, p according to one-way analysis of variance test followed by post-hoc Tukey test.


Table 1  — Reproductive process and infertility of rats in experimental groups.
Groups Male pups Female pups Total weight
n Mean ± SD p* p** n Mean ± SD p* p** n Mean ± SD
HG 31 5.20 ± 0.47 - <0.001 54 4.90 ± 0.66 - <0.001 85 5.01 ± 0.62
SC 10 3.90 ± 0.42 < 0.001 - 5 3.70 ± 0.61 < 0.001 - 15 3.83 ± 0.48
S + REG 30 5.00 ± 0.79 0.629 <0.001 26 4.70 ± 0.44 0.605 0.001 56 4.91 ± 0.66
Table 2  — Weight and gender differences of pups in experimental groups of rats
Groups Non-infertile rats n (%) Infertile rats n (%) p* Delay in maternity period (days) p**
HG (n = 6) 10 (100) 0 (0.0) 0.001 24 21 = 3 0.000
SC (n = 6) 2 (20) 8 (80) 42 21 = 21
S + REG (n = 6) 7 (70) 3 (30) 27 21 = 6
Figure 4.  — Histopathological changes of the experimental groups. (A) The ovarian tissue section of healthy group: the corpus luteum (star), developing follicular structures (arrows), subcapsular area (bidirectional arrow) (H&E, × 100). (B) Ovarian tissue of the stressed group section: diffuse congestion (stars) and hemorrhage (block arrows), fluid accumulation and inflammatory cell infiltrate in subcapsular area (black zigzag arrows), (H&E, × 100). (C) Ovarian tissue of the stressed group section: necrotic changes (arrow), congestion (star) and hemorrhage (block arrow) (H&E, × 200) (D) The ovarian tissue of the RRE-treated group: mild congestion (asterisk), subcapsular area without fluid accumulation and inflammatory cell infiltrate (bidirectional arrow) (H&E, × 100). (E) Ovarian tissue section of the RRE-treated group showing mild necrosis in the parenchymal stroma (bidirectional arrow), follicular structure (arrows) and corpus luteum (block arrow) (H&E, × 200).

[1] Mascarenhas M.N., Flaxman S.R., Boerma T., Vanderpoel S., Stevens G.A.: "National, regional, and global trends in infertility prevalence since 199.: a systematic analysis of 277 health surveys". PLoS Med., 2012, 9, 1001356.
[2] Sominsky L., Hodgson D.M., McLaughlin E.A., Smith R., Wall H.M., Spencer S.J.: "Linking stress and infertility: a novel role for ghrelin". Endocr. Rev., 2017, 38, 432-467.
doi: 10.1210/er.2016-1133 pmid: 28938425
[3] Geraghty A.C., Muroy S.E., Zhao S., Bentley G.E., Kriegsfeld L.J., Kaufer D.: "Knockdown of hypothalamic RFRP3 prevents chronic stress-induced infertility and embryo resorption". eLife, 2015, 4, 04316.
[4] Young A.J., Carlson A.A., Monfort S.L., Russell A.F., Bennett N.C., Clutton-Brock T.: "Stress and the suppression of subordinate reproduction in cooperatively breeding meerkats". Proc. Natl. Acad. Sci., 2006, 103, 12005-120010.
doi: 10.1073/pnas.0510038103 pmid: 16894179
[5] Damone A.L., Joham A.E., Loxton D., Earnest A., Teede H.J., Moran LJ.: "Depression, anxiety and perceived stress in women with and without PCOS: a community-based study". Psychol. Med., 2019, 49, 1510-1520.
doi: 10.1017/S0033291718002076 pmid: 30131078
[6] LakatosE., Szigeti J.F., Ujma P., Sexty R., Balog P.: "Anxiety and depression among infertile women: a cross-sectional survey from Hungary".. BMC Women's Health, 2017, 17, 48.
[7] Kessler R.C., Gruber M., Hettema J.M., Hwang I., Sampson N., Yonkers K.A.: "Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up". Psychol. Med., 2008, 38, 365-374.
doi: 10.1017/S0033291707002012 pmid: 18047766
[8] Pirkola S.P., Isometsä E., Suvisaari J., Aro H., Joukamaa M., Poikolainen K., et al.: "DSM-IV mood-, anxiety-and alcohol use disorders and their comorbidity in the Finnish general population". Soc. Psych. Psychiatr. Epidemiol., 2005, 40, 1.
doi: 10.1007/s00127-005-0848-7
[9] Rigucci S., Serafini G., Pompili M., Kotzalidis G.D., Tatarelli R.: "Anatomical and functional correlates in major depressive disorder: the contribution of neuroimaging studies".. World J. Biol Psychiatry, 2010, 11, 165-180.
doi: 10.1186/1471-244X-11-165 pmid: 21985179
[10] Atmaca M., Tezcan E., Kuloglu M., Ustundag B., Tunckol H.: "Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment". Eur. Arch. Psychiatry. Clin. Neurosci., 2004, 254, 231-235.
doi: 10.1007/s00406-004-0484-3 pmid: 15309392
[11] Irwin M.: “Immune correlates of depression”. Adv. Exp. Med. Biol., 1999, 461, 1-24.
doi: 10.1007/978-0-585-37970-8_1 pmid: 10442164
[12] Maddock C., Pariante C.M.: "How does stress affect you? An overview of stress, immunity, depression and disease". Epidemiol Psychiatr Sci., 2001, 10, 153-162.
[13] Alzarea S., Rahman S.: "Alpha-7 nicotinic receptor allosteric modulator PNU120596 prevents lipopolysaccharide-induced anxiety, cognitive deficit and depression-like behaviors in mice". Behav. Brain. Res., 2019, 366, 19-28.
doi: 10.1016/j.bbr.2019.03.019 pmid: 30877025
[14] Abolaji A.O., Adedara I.A., Abajingin A.O., Fatunmibi O.J., Ladipo E.O., Farombi E.O.: "Evidence of oxidative damage and reproductive dysfunction accompanying 4-vinylcyclohexene diepoxide exposure in female Wistar rats". Reproductive Toxicol., 2016, 66, 10-19.
doi: 10.1016/j.reprotox.2016.09.009
[15] Al-Gubory K.H., Fowler P.A., Garrel C.: "The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes". ‎Int. J. Biochem. Cell Biol., 2010, 42, 1634-1650.
[16] Kalagiri R.R., Carder T., Choudhury S., Vora N., Ballard A.R., Govande V., et al.: "Inflammation in complicated pregnancy and its outcome". Am. J. Perinatol., 2016, 33, 1337-1356.
doi: 10.1055/s-0036-1582397 pmid: 27159203
[17] Coors A., Brosch M., Kahl E., Khalil R., Michels B., Laub A., et al.: "Rhodiola rosea root extract has antipsychotic-like effects in rodent models of sensorimotor gating".. J. Ethnopharmacol., 2019, 235, 320-328.
doi: 10.1016/j.jep.2019.02.031 pmid: 30776471
[18] Juřica J., Koupá T.: "Rhodiola rosea and its neuropsychotropic effects". Ceska. Slov. Farm., 2016, 65, 87-93. [In Czech]
pmid: 27854435
[19] Palumbo D.R., Occhiuto F., Spadaro F., Circosta C.: "Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide‐induced cell death through reduction in the accumulation of intracellular calcium". Phytother. Res., 2012, 26, 878-883.
doi: 10.1002/ptr.3662 pmid: 22086763
[20] Doncheva N.D., Mihaylova A.S., Getova D.P.: "Antinociceptive and anti-inflammatory effects of Rhodiola rosea L. Extract in rats". Fol. Med., 2013, 55, 70-75.
[21] Aynaoglu Yildiz G., Yildiz D., Yapca O.E., Suleyman B., Arslan Y.K., Kurt N, et al.: "Effect of diazepam, sertraline and melatonin on the stress-induced reproductive disorders and intrauterine growth restriction in female rats". J. Matern. Fetal Neonatal. Med., 2019, 1-7.
doi: 10.1080/14767058.2020.1808615 pmid: 32814485
[22] Weydert C.J., Cullen J.J.: "Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue". Nat. Protoc., 2010, 5, 51-66.
doi: 10.1038/nprot.2009.197 pmid: 20057381
[23] Bradford M.M.: "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding". Anal. Biochem., 1976, 72, 248-254.
doi: 10.1006/abio.1976.9999 pmid: 942051
[24] Ohkawa H., Ohishi N., Yagi K.: "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction". Anal. Biochem., 1979, 95, 351-358.
doi: 10.1016/0003-2697(79)90738-3 pmid: 36810
[25] Sedlak J., Lindsay R.H.: "Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent". Anal. Biochem., 1968, 25, 192-205.
doi: 10.1016/0003-2697(68)90092-4 pmid: 4973948
[26] Erel O.: "A novel automated method to measure total antioxidant response against potent free radical reactions". Clin. Biochem., 2004, 37, 112-119.
doi: 10.1016/j.clinbiochem.2003.10.014
[27] Erel O.: "A new automated colorimetric method for measuring total oxidant status". Clin. Biochem., 2005, 38, 1103-1111.
doi: 10.1016/j.clinbiochem.2005.08.008 pmid: 16214125
[28] Yeum K.J., Russell R.M., Krinsky N.I., Aldini G.: "Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma". Arch. Biochem. Biophys., 2004, 430, 97-103.
doi: 10.1016/j.abb.2004.03.006 pmid: 15325916
[29] Kisaoglu A., Borekci B., Yapca O.E., Bilen H., Suleyman H.: "Tissue damage and oxidant/antioxidant balance". Eurasian J. Med., 2013, 45, 47-49.
doi: 10.5152/eajm.2013.08 pmid: 25610248
[30] Gutteridge J.: "Lipid peroxidation and antioxidants as biomarkers of tissue damage". Clin. Chem., 1995, 41, 1819-1828.
pmid: 7497639
[31] Davies K., Goldberg A.: "Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes". J. Biol. Chem., 1987, 262, 8220-8226.
pmid: 3597372
[32] Kuloglu M., Atmaca M., Tezcan E., Gecici Ö., Tunckol H., Ustundag B.: "Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder". Neuropsychobiology, 2002, 46, 27-32.
doi: 10.1159/000063573 pmid: 12207144
[33] Kuloglu M., Atmaca M., Tezcan E., Ustundag B., Bulut S.: "Antioxidant enzyme and malondialdehyde levels in patients with panic disorder". Neuropsychobiology, 2002, 46, 186-189.
doi: 10.1159/000067810 pmid: 12566935
[34] Süleyman H., Gül V., Erhan E.: "Oksidatif stres ve doku hasarı". Erzincan Tıp Dergisi., 2018, 1. [In Turkish]
[35] Liu J., Wang X., Mori A.: "Immobilization stress-induced antioxidant defense changes in rat plasma: effect of treatment with reduced glutathione". Inter. J Biochem., 1994, 26, 511-517.
doi: 10.1016/0020-711X(94)90008-6
[36] Hayden M.S., Ghosh S.: "NF-κB, the first quarter-century: remarkable progress and outstanding questions". Genes Dev.; 2012, 26, 203-234.
doi: 10.1101/gad.183434.111 pmid: 22302935
[37] Choi M.C., Jo J., Park J., Kang H.K., Park Y.: "NF-κB Signaling Pathways in Osteoarthritic Cartilage Destruction". Cells, 2019, 8, 734.
doi: 10.3390/cells8070734
[38] Olsson E.M., von Schéele B., Panossian A.G.: "A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue". Planta Med., 2009, 75, 105-112.
doi: 10.1055/s-0028-1088346 pmid: 19016404
[39] Darbinyan V., Aslanyan G., Amroyan E., Gabrielyan E., Malmström C., Panossian A.: "Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression". Nord. J. Psychiatry, 2007, 61, 343-348.
doi: 10.1080/08039480701643290 pmid: 17990195
[40] Zhou Q., Yin Z.P., Ma L., Zhao W., Hao H.W., Li H.L.: "Free radical-scavenging activities of oligomeric proanthocyanidin from Rhodiola rosea L. and its antioxidant effects in vivo". Nat. Prod. Res., 2014, 28, 2301-2303.
doi: 10.1080/14786419.2014.921786
[41] Aksoy A.N., Aydın F., Yılmaz E.P.T., Batmaz G., Suleyman B.: "The Effect of Controlled Reperfusion in the Prevention of Infertility Caused by Ischemia Induced in the Contralateral Ovary in Rats with Unilateral Ovariectomy". Gynecol. Obstet Invest., 2015, 80, 199-205.
doi: 10.1159/000377701 pmid: 25824941
[42] Unlubilgin E., Suleyman B., Balci G., Al R.A., Cankaya M., Nayki U.A., et al.: "Prevention of infertility induced by ovarian ischemia reperfusion injury by benidipine in rats: Biochemical, gene expression, histopathological and immunohistochemical evaluation".J. Gynecol. Obstet. Hum. Reprod., 2017, 46, 267-273.
doi: 10.1016/j.jogoh.2016.12.001 pmid: 28403925
[43] Zhou Q., Han X., Li R., Zhao W., Bai B., Yan C., et al.: "Anti-atherosclerosis of oligomeric proanthocyanidins from Rhodiola rosea on rat model via hypolipemic, antioxidant, anti-inflammatory activities together with regulation of endothelial function". Phytomedicine, 2018, 51, 171-180.
doi: 10.1016/j.phymed.2018.10.002 pmid: 30466614
[44] Smeenk J., Verhaak C., Eugster A., Van Minnen A., Zielhuis G., Braat D.: "The effect of anxiety and depression on the outcome of in-vitro fertilization". Hum. Reprod., 2001, 16, 1420-1423.
doi: 10.1093/humrep/16.7.1420 pmid: 11425823
[45] Yapca O.E., Kumbasar S., Salman S., Yarali O., Sener E., Mammadov R., et al.: "Controlled reperfusion for different durations in the treatment of ischemia-reperfusion injury of the rat ovary: evaluation of biochemical features, molecular gene expression, and histopathology". Can J Physiol Pharmacol., 2015, 93, 269-274.
doi: 10.1139/cjpp-2014-0359 pmid: 25730518
[46] Rödel H.G., Prager G., Stefanski V., von Holst D., Hudson R.: "Separating maternal and litter-size effects on early postnatal growth in two species of altricial small mammals". Physiol. Behav., 2008, 93, 826-834.
doi: 10.1016/j.physbeh.2007.11.047 pmid: 18187167
[1] H.J. Wang, T.H. Chou, Y.C. Lee, H.K. Au. Acute fatty liver during pregnancy and gestational diabetes insipidus: a case report[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(3): 438-441.
[2] J. W. Kim, Y. H. Kim, J. H. Moon, H. A. Jung, E. J. Noh. The efficacy of third-generation cephalosporin plus metronidazole versus third-generation cephalosporin plus clarithromycin in neonatal outcomes and oxidative stress markers in women with preterm premature rupture of membranes[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 194-198.
[3] S. J. Knight, A. D. Smith, H. Kim, A. C. Collier. Human placental suppressors of cytokine signalling (SOCS) and inflammatory cytokines are dysregulated in assisted reproduction, advanced maternal age and pre-term birth[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 277-286.
[4] Hue HJ, Kim SK, Choi JY, Suh DH, Kim KD, No JH, Lee JR, Jee BC, Kim YB, Jeon HW. Previous ovarian surgery increases the risk of tubal factor infertility[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(1): 84-88.
[5] M. Minase, T. Miyamoto, N. Hayashi, G. Minase, K. Nishiwaki, K. Sengoku. A patient with a didelphys vaginal septum and infertility diagnosed by laparoscopy and magnetic resonance imaging[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(6): 988-989.
[6] E.G. Aydeniz, U. Sari, T.U.K. Dilek. Pregnancy success rate at recurrent implantation failure patients after hysteroscopic endometrial injury: preliminary study[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(5): 709-712.
[7] J. Jeong, J. Yang, Y. J. Song, Y. J. Na, H. G. Kim. A case report of acute ovarian cyst torsion by female adnexal tumor of probable Wölffian origin[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(5): 824-827.
[8] K. Kitaya, Y. Takaya, R. Nishiyama, K. Yamaguchi, H. Matsubayashi, T. Takeuchi, S. Mizuta, T. Ishikawa. Myoinositol supplementation on intracytoplasmic sperm injection outcome in Japanese infertile polycystic ovarian syndrome women with non-obese less-androgenic phenotype: a prospective controlled observational study[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(4): 549-552.
[9] H. Kwon, J. E. Shin, H. Kim. A novel treatment of severe dysmenorrhea due to adenomyosis: a case series of 3 infertile patients treated with dopamine agonist and in vitro fertilization-embryo transfer resulting in successful pregnancy[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(4): 637-640.
[10] P. Fuchs, I. Czech, A. Fuchs, J. Sikora. Use of neutral argon plasma in the treatment of endometriosis initial findings[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(3): 434-436.
[11] J.H. Check, J. Liss, D. Check. The beneficial effect of luteal phase support on pregnancy rates in women with unexplained infertility[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(3): 447-449.
[12] I. Rudic Biljic-Erski, M. Vasiljevic, S. Rakic, S. Mihajlovic, O.D. Smiljkovic. The impact of hysteroscopic myomectomy on fertility and pregnancy outcomes of infertile women according characteristics of submucous fibroids[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(2): 235-240.
[13] Chunjuan Shen, Liping Wang, Xiaojie Wu, Shuhui Mao, Chunxia Fang. The relationship between vitamin D and IVF: a systematic review and meta-analysis[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(1): 12-15.
[14] Xiao-Li Zhang, Wei-ping Li, Zhong-Yu Liu, Yuan-Qing Yao, Hong-Xu. The auto-transplantation of uterus in swine: surgical techniques and long-term graft survival[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(1): 21-26.
[15] N. Danandeh Osgui, P. Bastani. Improvement of concomitant symptoms of pelvic organ prolapsed with applied pessary[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(1): 42-44.
No Suggested Reading articles found!