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Hekmat, S., Sharifzadeh, M., Toliyat, T., Savary Kouzehkonan, R., Mehri Ardestani, M., Tabarrai, M., & Sadati Lamardi, S. N. (2024). Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 22(2), 111–126. https://doi.org/10.18502/ijrm.v22i2.15708
https://doi.org/10.18502/ijrm.v22i2.15708
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Sharareh Hekmat
Sharareh Hekmat
Department of Traditional Pharmacy, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Mohammad Sharifzadeh
Mohammad Sharifzadeh
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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Tayebeh Toliyat
Tayebeh Toliyat
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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Roghayeh Savary Kouzehkonan
Roghayeh Savary Kouzehkonan
Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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Mozhgan Mehri Ardestani
Mozhgan Mehri Ardestani
Department of Persian Medicine, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.
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Malihe Tabarrai
Malihe Tabarrai
Department of Persian Medicine, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Seyede Nargess Sadati Lamardi
Seyede Nargess Sadati Lamardi
Department of Traditional Pharmacy, School of Traditional Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Published Date
- Mar 25, 2024
Urtica pilulifera L. seed extract promotes folliculogenesis and alleviates the diminished ovarian reserve in the Balb/c mice model: An experimental study
Abstract
Background: Urtica pilulifera L. seed (UPS) is a Persian traditional medicine prescription that positively affects female infertility.
Objective: This study aimed to evaluate the beneficial effects of UPS on a diminished ovarian reserve (DOR) model induced by cyclophosphamide in Balb/c mice.
Materials and Methods: A single intraperitoneal (75 mg/kg) of cyclophosphamide was administered to establish a DOR model. 25 female Balb/c mice (6–8 wk, 25 ± 2 gr) were randomly divided into 5 groups (n = 5/each), including control (normal saline), model (DOR), DOR+50, DOR+100, and DOR+200 (mg/kg UPS, gavage) groups for 14 days. The levels of follicle-stimulating hormone, luteinizing hormone, estradiol, malondialdehyde, superoxide dismutases, apoptosis, and histopathological alterations were analyzed. Gas chromatography-mass spectrometry analysis was performed to identify the phytochemicals of the UPS.
Results: It was observed that the UPS extract reduced malondialdehyde concentration and apoptosis in the DOR model as well as enhanced superoxide dismutases activity in the ovaries in a dose-dependent manner. Moreover, it exerted a modulatory effect on steroidal hormones such as follicle-stimulating hormone, luteinizing hormone, and estradiol. The histopathological analysis revealed the therapeutic potential of the UPS extract. The main chemical components of UPS were linoleic acid (59.25%), n-hexadecanoic acid (10.36%), and oleic acid (8.29%).
Conclusion: The results indicated that the UPS extract has therapeutic potential in the DOR model. This potential is attributed to the reduction of oxidative stress, modulation of apoptosis, and regulation of steroidal hormones that may be associated with the observed beneficial effects of fatty acids on fertility improvement.
Key words: Apoptosis, Fatty acids, Female infertility, Herbal medicine, Persian medicine, Oxidative stress.
References
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[27] Hamzeh M, Hosseinimehr SJ, Mohammadi HR, Yaghubi Beklar S, Dashti A, Talebpour Amiri F. Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study. Int J Reprod BioMed 2018; 16: 323–334.
[28] Amawi KF, Alkhatib AJ. Urtica Pilulifera in treating pre-diabetic rat model to control the blood glucose, lipids and oxidative stress. Med Arch 2020; 74: 168.
[29] Jahangirifar M, Taebi M, Nasr-Esfahani MH, HeidariBeni M, Asgari GH. Dietary fatty acid intakes and the outcomes of assisted reproductive technique in infertile women. J Reprod Infertil 2021; 22: 173.
[30] Fayezi S, Leroy JL, Novin MG, Darabi M. Oleic acid in the modulation of oocyte and preimplantation embryo development. Zygote 2018; 26: 1–13.
[31] Skoracka K, Ratajczak AE, Rychter AM, Dobrowolska A, Krela-Kaźmierczak I. Female fertility and the nutritional approach: The most essential aspects. Adv Nutr 2021; 12: 2372–2386.
[32] Deghima A, Righi N, Daoud I, Ansorena D, Astiasarán I, Bedjou F. Fatty acid composition, acute toxicity and anti-inflammatory activity of the n-hexane extract from Ranunculus macrophyllus Desf. roots. South Afr J Botany 2022; 148: 315–325.
[33] Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: Follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril 2015; 103: 303–316.
[34] Fan Y, Chang Y, Wei L, Chen J, Li J, Goldsmith S, et al. Apoptosis of mural granulosa cells is increased in women with diminished ovarian reserve. J Assist Reprod Genet 2019; 36: 1225–1235.
[35] Qi Q, Zhang X, Yao L, Chen Y, Weng H. Pueratin improves diminished ovarian reserve by inhibiting apoptosis. Exp Ther Med 2021; 22: 1423.
[36] Feng J, Ma WW, Li HX, Pei XY, Deng SL, Jia H, et al. Melatonin prevents cyclophosphamideinduced primordial follicle loss by inhibiting ovarian granulosa cell apoptosis and maintaining AMH expression. Front Endocrinol 2022; 13: 895095.
[37] Lande Y, Fisch B, Tsur A, Farhi J, Prag-Rosenberg R, Ben-Haroush A, et al. Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro. Reprod Biomed Online 2017; 34: 104–114.
[2] Xu J-Y, Zhao A-L, Xin P, Geng J-Z, Wang B-J, Xia T. Acupuncture for female infertility: Discussion on action mechanism and application. Evid Based Complement Alternat Med 2022; 2022: 3854117.
[3] Akbaribazm M, Goodarzi N, Rahimi M. Female infertility and herbal medicine: An overview of the new findings. Food Sci Nutr 2021; 9: 5869–5882.
[4] Yan F, Zhao Q, Li Y, Zheng Zh, Kong X, Shu Ch, et al. The role of oxidative stress in ovarian aging: A review. J Ovarian Res 2022; 15: 100.
[5] Eftekhari Moghadam AR, Taheri Moghadam M, Hemadi M, Saki Gh. Oocyte quality and aging. JBRA Assist Reprod 2022; 26: 105–122.
[6] Huang C, Song K, Ma W, Ding J, Chen Zh, Zhang M. Immunomodulatory mechanism of Bushen Huoxue Recipe alleviates cyclophosphamide-induced diminished ovarian reserve in mouse model. J Ethnopharmacol 2017; 208: 44–56.
[7] Rasool S, Shah D. Fertility with early reduction of ovarian reserve: The last straw that breaks the Camel’s back. Fertil Res Pract 2017; 3: 15.
[8] Park SU, Walsh L, Berkowitz K. Mechanisms of ovarian aging. Reproduction 2021; 162: 19–33.
[9] Roberts H, Hickey M, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia: A cochrane review summary. Maturatis 2014; 77: 4–6.
[10] Ekor M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 2014; 4: 177.
[11] Abu-Odeh AM, Talib WH. Middle east medicinal plants in the treatment of diabetes: A review. Molecules 2021; 26: 742.
[12] Jafari Z, Samani SA, Jafari M. Insights into the bioactive compounds and physico-chemical characteristics of the extracted oils from Urtica dioica and Urtica pilulifera. SN Appl Sci 2020; 2: 416.
[13] Kazemeini SK, Emtiazy M, Owlia F, Khani P. Causes of infertility in view of Iranian traditional medicine: A review. Int J Reprod BioMed 2017; 15: 187–194.
[14] Tansaz M, Sohrabvand F, Adhami S, Keshavarz M, Dabaghian FH, Bioos S, et al. Evaluation of uterine temperament in Iranian infertile women using a quantitative instrument for uterine temperament detection. Int J Prev Med 2020; 11: 39.
[15] Saeidi A, Tansaz M, Saberi M, Ebadi A, Tabarrai M, Hashemi M, et al. Evaluation of uterine warm and cold distemperament (Su-e Mizaj) in Persian medicine: A qualitative study. Cresent J Med Biol Sci 2020; 7: 177–185.
[16] Shirazi A. Makhzan al-adviyah (The storehouse of medicaments). Tehran: Tehran University of Medical Sciences Press; 2009.
[17] Jiang M, Wang W, Zhang J, Wang C, Bi Y, Li P, et al. Protective effects and possible mechanisms of actions of Bushen Cuyun recipe on diminished ovarian reserve induced by cyclophosphamide in rats. Front Pharmacol 2020; 11: 546.
[18] Wick MR. The hematoxylin and eosin stain in anatomic pathology- an often-neglected focus of quality assurance in the laboratory. Semin Diagn Pathol 2019; 36: 303–311.
[19] Rieppo L, Janssen L, Rahunen K, Lehenkari P, Finnilä MAJ, Saarakkala S. Histochemical quantification of collagen content in articular cartilage. PLoS One 2019; 14: e0224839.
[20] Song W, Liu M-L, Zhao Zh-J, Huang Ch-Q, Xu J-W, Wang A-Q, et al. SIRT1 inhibits high shear stressinduced apoptosis in rat cortical neurons. Cell Mol Bioeng 2020; 13: 621–631.
[21] Bulbul M, Tekce A, Annac E, Korkmaz O, Onderci M, Korkmaz D, et al. Identification of royal jelly as a potential new drug to protect the ovarian reserve and uterus against cyclophosphamide in rats. Clin Exp Reprod Med 2023; 50: 34–43.
[22] Buigues A, Marchante M, Herraiz S, Pellicer A. Diminished ovarian reserve chemotherapyinduced mouse model: A tool for the preclinical assessment of new therapies for ovarian damage. Reprod Sci 2019: 1933719119831784.
[23] Ethical guidelines for educational research. 4th Ed. London, British Educational Research Association[BERA]; 2018.
[24] Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA 2017; 318: 1367–1376.
[25] Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol 2018; 16: 80.
[26] Özcan P, Fıçıcıoğlu C, Yıldırım ÖK, Özkan F, Akkaya H, Aslan I. Protective effect of resveratrol against oxidative damage to ovarian reserve in female Sprague-Dawley rats. Reprod BioMed Online 2015; 31: 404–410.
[27] Hamzeh M, Hosseinimehr SJ, Mohammadi HR, Yaghubi Beklar S, Dashti A, Talebpour Amiri F. Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study. Int J Reprod BioMed 2018; 16: 323–334.
[28] Amawi KF, Alkhatib AJ. Urtica Pilulifera in treating pre-diabetic rat model to control the blood glucose, lipids and oxidative stress. Med Arch 2020; 74: 168.
[29] Jahangirifar M, Taebi M, Nasr-Esfahani MH, HeidariBeni M, Asgari GH. Dietary fatty acid intakes and the outcomes of assisted reproductive technique in infertile women. J Reprod Infertil 2021; 22: 173.
[30] Fayezi S, Leroy JL, Novin MG, Darabi M. Oleic acid in the modulation of oocyte and preimplantation embryo development. Zygote 2018; 26: 1–13.
[31] Skoracka K, Ratajczak AE, Rychter AM, Dobrowolska A, Krela-Kaźmierczak I. Female fertility and the nutritional approach: The most essential aspects. Adv Nutr 2021; 12: 2372–2386.
[32] Deghima A, Righi N, Daoud I, Ansorena D, Astiasarán I, Bedjou F. Fatty acid composition, acute toxicity and anti-inflammatory activity of the n-hexane extract from Ranunculus macrophyllus Desf. roots. South Afr J Botany 2022; 148: 315–325.
[33] Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: Follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril 2015; 103: 303–316.
[34] Fan Y, Chang Y, Wei L, Chen J, Li J, Goldsmith S, et al. Apoptosis of mural granulosa cells is increased in women with diminished ovarian reserve. J Assist Reprod Genet 2019; 36: 1225–1235.
[35] Qi Q, Zhang X, Yao L, Chen Y, Weng H. Pueratin improves diminished ovarian reserve by inhibiting apoptosis. Exp Ther Med 2021; 22: 1423.
[36] Feng J, Ma WW, Li HX, Pei XY, Deng SL, Jia H, et al. Melatonin prevents cyclophosphamideinduced primordial follicle loss by inhibiting ovarian granulosa cell apoptosis and maintaining AMH expression. Front Endocrinol 2022; 13: 895095.
[37] Lande Y, Fisch B, Tsur A, Farhi J, Prag-Rosenberg R, Ben-Haroush A, et al. Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro. Reprod Biomed Online 2017; 34: 104–114.