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Khani, S., Abdollahi, M., Khalaj, A., Heidari, H., & Zohali, S. (2021). The effect of hydroalcoholic extract of Nigella Sativa seed on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 19(3), 271–282. https://doi.org/10.18502/ijrm.v19i3.8575
https://doi.org/10.18502/ijrm.v19i3.8575
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- Cited by 3 articles
authors
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Samira Khani
Samira Khani
Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
-
Maasoume Abdollahi
Maasoume Abdollahi
Department of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran
-
Azam Khalaj
Azam Khalaj
Department of Physiology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
-
Hamid Heidari
Hamid Heidari
Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
-
Somaye Zohali
Somaye Zohali
Student Research Committee, Qom University of Medical Sciences, Qom, Iran
Published Date
- Mar 21, 2021
The effect of hydroalcoholic extract of Nigella Sativa seed on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: An experimental study
Abstract
Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women.
Objective: The aim of this study was to investigate the therapeutic effect of hydroalcoholic extract of Nigella sativa (N. sativa) seed as a plant, the consumption of which has been recommended in Islam, on dehydroepiandrosterone (DHEA)-induced PCOS rats.
Materials and Methods: This experimental study was carried out on 36 Wistar female rats (3 wk, 60 ± 10 gr). Then rats were divided into 6 groups (n = 6/each): control; PCOSinduced (DHEA 60 mg/kg/sc); PCOS + Metformine (30 mg/kg); and three experimental groups receiving DHEA + hydroalcoholic extract of N. sativa seeds in doses of 50, 100 and 200 mg/kg, respectively. Blood samples were taken for the evaluation of sexual hormones, oxidative stress, glucose, and insulin after 30 days of treatment. Ovarian tissue was used for histopathological study.
Results: The serum levels of luteinizing hormone, testosterone, glucose, insulin resistance, malondialdehyde, and insulin (p ≤ 0.001) and estrogen increased while the levels of progesterone (p = 0.01) and antioxidant enzymes in the PCOS group decreased (p ≤ 0.001).
Conclusion: The administration of the N. sativa extract to the PCOS rats resulted in remarkable changes in the serumic factors relative to the PCOS group. In addition, the extract improved the structure of the ovarian tissue in the PCOS rat. The histopathological results which are in accordance with biochemical findings imply that N. sativa seed could be useful in the treatment of PCOS, the higher doses of the extract being more effective.
Key words: Nigella sativa seed, Oxidative stress, Insulin resistance, Polycystic ovary syndrome, Rat.
References
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[15] Goudarzi M, Mombeini MA, Fatemi I, Aminzadeh A, Kalantari H, Nesari A, et al. Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol Res 2019; 41: 419– 428.
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[17] Ahangarpour A, Heidari H, Salehizade Junghani M, Absari R, Khoogar M, Ghaedi E. Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamidestreptozotocin- induced type II diabetic male mice. Res Pharm Sci 2017; 12: 416–424.
[18] Mehrzadi S, Bahrami N, Mehrabani M, Motevalian M, Mansouri E, Goudarzi M. Ellagic acid: A promising protective remedy against testicular toxicity induced by arsenic. Biomed Pharmacother 2018; 103: 1464–1472.
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[20] Walters KA, Allan CM, Handelsman DJ. Rodent models for human polycystic ovary syndrome. Biol Reprod 2012; 86: 149. 1–12.
[21] Sudhir SP, Deshmukh VO, Verma HN. Nigella sativa seed, a novel beauty care ingredient: A review. Int J Pharm Sci Res 2016; 7: 3185–3196.
[22] Parhizkar S, Latiff LA, Rahman SA, Dollah MA, Parichehr H. Assessing estrogenic activity of Nigella sativa in ovariectomized rats using vaginal cornification assay. Afr J Pharm Pharmacol 2011; 5: 137–142.
[23] Khodaii H, Chamani M, Sadeghi A, Hejazi H. Effects of conjugated linoleic acid on mouse factors and hormones in the process of ovulation in miceintint. J Fertil 2009; 2: 101–109.
[24] Atashpour S, Jahromi HK, Jahromi ZK, Maleknasab M. Comparison of the effects of Ginger extract with clomiphene citrate on sex hormones in rats with polycystic ovarian syndrome. Int J Reprod BioMed 2017; 15: 561–568.
[25] Jahan S, Abid A, Khalid S, Afsar T, Ul-Ain Q, Shaheen G, et al. Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: A histological and a biochemical study. J Ovarian Res 2018; 11: 26–35.
[26] Heshmati J, Namazi N. Effects of black seed (Nigella sativa) on metabolic parameters in diabetes mellitus: A systematic review. Complement Ther Med 2015; 23: 275–282.
[27] Ermumcu MŞ, Şanlıer N. black cumin (Nigella sativa) and its active component of thymoquinone: Effects on health. Food and Health 2017; 3: 170–183.
[28] Rezvanfar MA, Shojaei Saadi HA, Gooshe M, Abdolghaffari AH, Baeeri M, Abdollahi M. Ovarian aging-like phenotype in the hyperandrogenisminduced murine model of polycystic ovary. Oxid Med Cell Longev 2014; 2014: 1–10.
[29] Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, et al. Chemerin is associated with metabolic syndromephenotypes in a Mexican-American population. J Clin Endocrinol Metab 2009; 94: 3085–3088.
[30] Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148: 4687–4694.
[31] Tan BK, Chen J, Farhatullah S, Adya R, Kaur J, Heutling D, et al. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 2009; 58: 1971–1977.
[32] Ibrahim RM, Hamdan NS, Ismail M, Saini SM, Rashid SNA, Latiff LA, et al. Protective effects of Nigella sativa on metabolic syndrome in menopausal women. Adv Pharm Bull 2014; 4: 29– 33.
[33] Vanamala J, Kester AC, Heuberger AL, Reddivari L. Mitigation of obesity-promoted diseases by Nigella sativa and thymoquinone. Plant Foods Hum Nutr 2012; 67: 111–119.
[34] Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev 2016; 2016: 8589318: 1–15.
[35] Rezvanfar MA, Rezvanfar MA, Ahmadi A, Shojaei Saadi HA, Baeeri M, Abdollahi M. Mechanistic links between oxidative/nitrosative stress and tumor necrosis factor alpha in letrozole-induced murine polycystic ovary: Biochemical and pathological evidences for beneficial effect of pioglitazone. Hum Exp Toxicol 2012; 31: 887–897.
[36] Leong XF, Rais Mustafa M, Jaarin K. Nigella sativa and its protective role in oxidative stress and hypertension. Evidence-Based Complementary and Alternative Medicine 2013; 2013: 120732: 1–10.
[37] Nader MA, El-Agamy DS, Suddek GhM. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 2010; 33: 637–643.
[38] Inci M, Davarci M, Inci M, Motor S, Yalcinkaya FR, Nacar E, et al. Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis. Hum Exp Toxicol 2013; 32: 354–361.
[39] Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indones 2014; 23: 239–244.
[40] Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev 2007; 28: 117–149.
[2] Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2014; 6: 1–13.
[3] Banaszewska B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Lipids in polycystic ovary syndrome: Role of hyperinsulinemia and effects of metformin. Am J Obstet Gynecol 2006; 194: 1266–1272.
[4] Duleba AJ. Medical management of metabolic dysfunction in PCOS. Steroids 2012; 77: 306–311.
[5] Omidi M, Ahangarpour A, Mard SA, Khorsandi L. The effects of myricitrin and vitamin E against reproductive changes induced by D-galactose as an aging model in female mice: An experimental study. Int J Reprod BioMed 2019; 17: 789–798.
[6] Atiomo WU, El-Mahdi E, Hardiman P. Familial associations in women with polycystic ovary syndrome. Fertil Steril 2003; 80: 143–145.
[7] Amirghofran Z. Medicinal plants as immunosuppressive agents in traditional Iranian medicine. Iran J Immunol 2010; 7: 65–73.
[8] Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17: 299–305.
[9] Ghannadi A, Hajhashemi V, Jafarabadi H. An investigation of the analgesic and antiinflammatory effects of Nigella sativa seed polyphenols. J Med Food 2005; 8: 488–493.
[10] Panahi M, Namjoyan F, Shakerin Z. Evaluation of antioxidant effects of nigella sativa extract on the ultra structure of neural tube defects in diabetic rats’s offspring. Jundishapur J Nat Pharm Products 2011; 6: 16–23.
[11] Kim EJ, Jang M, Choi JH, Park KS, Cho IH. An improved dehydroepiandrosterone-induced rat model of polycystic ovary syndrome (PCOS): Post-pubertal improve PCOS’s features. Front Endocrinol 2018; 9: 1–28.
[12] Ahangarpour A, Heidari H, Oroojan AA, Mirzavandi F, Nasr Esfehani K, Dehghan Mohammadi Z. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamidestreptozotocin induced type 2 model of diabetes in male mice. Avicenna J Phytomed 2017; 7: 169–179.
[13] Javadi I, Rashidi Nooshabadi M, Goudarzi M, Roudbari R. Protective effects of celery (Apium graveloens) seed extract on bleomycin-induced pulmonary fibrosis in rats. J Babol Univ Med Sci 2015; 17: 70–76.
[14] Jelodar Gh, Masoomi S, Rahmanifar F. Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model. Iran J Basic Med Sci 2018; 21: 645–650.
[15] Goudarzi M, Mombeini MA, Fatemi I, Aminzadeh A, Kalantari H, Nesari A, et al. Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol Res 2019; 41: 419– 428.
[16] Zamami Y, Takatori S, Goda M, Koyama T, Iwatani Y, Jin X, et al. Royal jelly ameliorates insulin resistance in fructose-drinking rats. Biol Pharm Bull 2008; 31: 2103–2107.
[17] Ahangarpour A, Heidari H, Salehizade Junghani M, Absari R, Khoogar M, Ghaedi E. Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamidestreptozotocin- induced type II diabetic male mice. Res Pharm Sci 2017; 12: 416–424.
[18] Mehrzadi S, Bahrami N, Mehrabani M, Motevalian M, Mansouri E, Goudarzi M. Ellagic acid: A promising protective remedy against testicular toxicity induced by arsenic. Biomed Pharmacother 2018; 103: 1464–1472.
[19] Luo LL, Huang J, Fu YC, Xu JJ, Qian YS. Effects of tea polyphenols on ovarian development in rats. J Endocrinol Invest 2008; 31: 1110–1118.
[20] Walters KA, Allan CM, Handelsman DJ. Rodent models for human polycystic ovary syndrome. Biol Reprod 2012; 86: 149. 1–12.
[21] Sudhir SP, Deshmukh VO, Verma HN. Nigella sativa seed, a novel beauty care ingredient: A review. Int J Pharm Sci Res 2016; 7: 3185–3196.
[22] Parhizkar S, Latiff LA, Rahman SA, Dollah MA, Parichehr H. Assessing estrogenic activity of Nigella sativa in ovariectomized rats using vaginal cornification assay. Afr J Pharm Pharmacol 2011; 5: 137–142.
[23] Khodaii H, Chamani M, Sadeghi A, Hejazi H. Effects of conjugated linoleic acid on mouse factors and hormones in the process of ovulation in miceintint. J Fertil 2009; 2: 101–109.
[24] Atashpour S, Jahromi HK, Jahromi ZK, Maleknasab M. Comparison of the effects of Ginger extract with clomiphene citrate on sex hormones in rats with polycystic ovarian syndrome. Int J Reprod BioMed 2017; 15: 561–568.
[25] Jahan S, Abid A, Khalid S, Afsar T, Ul-Ain Q, Shaheen G, et al. Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: A histological and a biochemical study. J Ovarian Res 2018; 11: 26–35.
[26] Heshmati J, Namazi N. Effects of black seed (Nigella sativa) on metabolic parameters in diabetes mellitus: A systematic review. Complement Ther Med 2015; 23: 275–282.
[27] Ermumcu MŞ, Şanlıer N. black cumin (Nigella sativa) and its active component of thymoquinone: Effects on health. Food and Health 2017; 3: 170–183.
[28] Rezvanfar MA, Shojaei Saadi HA, Gooshe M, Abdolghaffari AH, Baeeri M, Abdollahi M. Ovarian aging-like phenotype in the hyperandrogenisminduced murine model of polycystic ovary. Oxid Med Cell Longev 2014; 2014: 1–10.
[29] Bozaoglu K, Segal D, Shields KA, Cummings N, Curran JE, Comuzzie AG, et al. Chemerin is associated with metabolic syndromephenotypes in a Mexican-American population. J Clin Endocrinol Metab 2009; 94: 3085–3088.
[30] Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148: 4687–4694.
[31] Tan BK, Chen J, Farhatullah S, Adya R, Kaur J, Heutling D, et al. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 2009; 58: 1971–1977.
[32] Ibrahim RM, Hamdan NS, Ismail M, Saini SM, Rashid SNA, Latiff LA, et al. Protective effects of Nigella sativa on metabolic syndrome in menopausal women. Adv Pharm Bull 2014; 4: 29– 33.
[33] Vanamala J, Kester AC, Heuberger AL, Reddivari L. Mitigation of obesity-promoted diseases by Nigella sativa and thymoquinone. Plant Foods Hum Nutr 2012; 67: 111–119.
[34] Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid Med Cell Longev 2016; 2016: 8589318: 1–15.
[35] Rezvanfar MA, Rezvanfar MA, Ahmadi A, Shojaei Saadi HA, Baeeri M, Abdollahi M. Mechanistic links between oxidative/nitrosative stress and tumor necrosis factor alpha in letrozole-induced murine polycystic ovary: Biochemical and pathological evidences for beneficial effect of pioglitazone. Hum Exp Toxicol 2012; 31: 887–897.
[36] Leong XF, Rais Mustafa M, Jaarin K. Nigella sativa and its protective role in oxidative stress and hypertension. Evidence-Based Complementary and Alternative Medicine 2013; 2013: 120732: 1–10.
[37] Nader MA, El-Agamy DS, Suddek GhM. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 2010; 33: 637–643.
[38] Inci M, Davarci M, Inci M, Motor S, Yalcinkaya FR, Nacar E, et al. Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis. Hum Exp Toxicol 2013; 32: 354–361.
[39] Banjarnahor SDS, Artanti N. Antioxidant properties of flavonoids. Med J Indones 2014; 23: 239–244.
[40] Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev 2007; 28: 117–149.