Abstract
Polycystic ovary syndrome (PCOS) is a gynecological disorder among reproductive-aged women and a major cause of infertility. Different treatment options are being employed but with side effects. This has mandated alternative treatment options, especially complementary therapy. This study therefore investigated the possible protective effects of methanol extract of Drymaria cordata in Letrozole-induced PCOS. The plant is folklorically used in the treatment of diverse ailments including PCOS, fibroids, uterine/ovarian/breast tumors, and cancers. Forty-eight female Wistar rats were acclimatized and initially divided into two groups: group I(control group) and group II(PCOS group). PCOS was induced by the oral administration of letrozole/high-fat diet for 21 days. After the induction, the PCOS group was sub-divided into four groups (n = 4): group II (positive control with PCOS), group III (MET 2mg/kg), group IV (MEDC 200mg/kg), and group V (MEDC 400mg/kg). Rats were orally treated with MET and MEDC for six weeks after the PCOS induction. At the end of the experimental period, blood samples were collected, sera were separated, mitochondria were isolated, and the mPT, some apoptotic biomarkers, hormonal and lipid profiles, and oxidative stress markers were determined. Ovarian histological evaluation and GC–MS analysis of MEDC were carried out. There was no significant mPT pore opening in the PCOS (untreated) group. However, treatments with MEDC caused significant mPT pore opening, upraised caspase 9, caspase 3, and Bax, and decreased anti-apoptotic Bcl-2 levels. The MEDC treatments restored the hormonal and lipid profiles, increased the levels of GSH-Px and SOD and decreased TBARS. Histological examination revealed resolved ovarian cysts and improved follicular growth with MEDC treatments. Comparable results were observed for both MEDC and metformin. The GC–MS analysis revealed the presence of some major pharmacologically relevant compounds. These findings suggest that MEDC contains phytochemicals that can protect against letrozole-induced PCOS possibly by normalizing the impaired hormonal balance, restoring the lipid profile, and improving the antioxidant milieu of the system.
Graphical Abstract
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On request.
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Not applicable.
Abbreviations
- mPT:
-
Mitochondrial permeability transition
- NTA:
-
No triggering agent
- TA:
-
Triggering agent
- MEDC:
-
Methanol extract of Drymaria cordata
- MET:
-
Metformin
- PCOS:
-
Polycystic ovary syndrome
- GnRH:
-
Gonadotropin-releasing hormone
- BAX:
-
BCL2-associated X protein
- BCL-2:
-
B-cell lymphoma 2
- SOD:
-
Superoxide dismutase
- GSH-Px:
-
Glutathione peroxidase
- ROS:
-
Reactive oxygen specie
- LDL:
-
Low density lipoprotein
- TC:
-
Total cholesterol
- HDL:
-
High density lipoprotein
- FSH:
-
Follicle stimulating hormone
- E2:
-
Estradiol
- T:
-
Testosterone
- TG:
-
Triglycerides
- LH:
-
Luteinizing hormone
- TBARS:
-
Thiobarbituric acid reactive species
- GC-MS:
-
Gas Chromatography-Mass Spectroscopy
References
Rowe JP, Comhaire FH, Hargreave JB, Mellows HJ. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press; 1993. 83p.
Yemele MD, Telefo PB, Lienou LL, Tagne SR, Fodouop CS, Goka CS, Lemfack MC, Moundipa FP. Ethnobotanical survey of medicinal plants used for pregnant women׳s health conditions in Menoua division-West Cameroon. J Ethnopharmacol. 2015;160:14–31.
Kamel HH. Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;168:60–3.
Kwon CY, Cho IH, Park KS. Therapeutic effects and mechanisms of herbal medicines for treating polycystic ovary syndrome: a review. Front Pharmacol. 2020;11:1192.
Goswami PK, Khale A. Natural remedies for Polycystic Ovarian Syndrome (PCOS): a review. Int J Pharm Phytopharm Res. 2012;1:396–402.
Burt Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC. Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids. 2012;77(4):332–7.
Plaza-Parrochia F, Bacallao K, Poblete C, Gabler F, Carvajal R, Romero C, et al. The role of androst-5-ene3beta,17beta-diol (androstenediol) in cell proliferation in endometrium of women with polycystic ovary syndrome. Steroids. 2014;89:11–9.
Giudice LC. Endometrium in PCOS: implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab. 2006;20(2):235–44.
Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1066–77.
Mohammadi M. Oxidative stress and polycystic ovary syndrome: a brief review. Int J Prev Med. 2019;10:86.
Amini L, Tehranian N, Movahedin M, Tehrani FR, Ziaee S. Antioxidants and management of polycystic ovary syndrome in Iran: A systematic review of clinical trials, Iran. J Reprod Med. 2015;13:1–8.
Zeng X, Huang Q, Long SL, Zhong Q, Mo Z. Mitochondrial dysfunction in polycystic ovary syndrome. DNA Cell Biol. 2020;39(8):1401–9.
Legro RS. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551–66.
Burkill HM. The useful plants of West Tropical Africa. 2nd Edn. Vol. 1. Royal Botanic Gardens, Kew; 1985. pp. 343.
Abasian Z, Rostamzadeh A, Mohammadi M, Hosseini M, Rafieian-Kopaei M. A review on role of medicinal plants in polycystic ovarian syndrome: Pathophysiology, neuroendocrine signaling, therapeutic status and future prospects. Middle East Fertil Soc J. 2018;23:255–62.
Wang H, Ruan X, Li Y, Cheng J, Mueck AO. Oxidative Stress Indicators in Chinese Women with PCOS and Correlation with Features of Metabolic Syndrome and Dependency on Lipid Patterns. Arch Gynecol Obstet. 2019;300:1413–21.
Telefo PB, Lienou LL, Yemele MD, Lemfack MC, Mouokeu C, Goka CS, Moundipa FP. Ethnopharmacological survey of plants used for the treatment of female infertility in Baham, Cameroon. J Ethnopharmacol. 2011;136(1):178–87.
Nono NR, Nzowa KL, Barboni L, Tapondjou AL. Drymaria cordata (Linn.) Willd (Caryophyllaceae): ethnobotany. Pharmacol Phytochem. 2014. https://doi.org/10.4236/abc.2014.42020.
Farnsworth NR. Biological and phytochemical screening of plants. Science. 1966;151:874–5.
Olowofolahan AO, Fatunsin OA, Olorunsogo OO. Modulatory effect of ciprofloxacin; a broad spectrum antibacterial drug, on mPT pore using rat model with estradiol benzoate-induced endometrial hyperplasia. Naunyn Schmiedebergs Arch Pharmacol. 2023. https://doi.org/10.1007/s00210-023-02824-8.
Singla S, Pradhan J, Thakur R, Goyal S. Drymaria cordata: Review on its pharmaconosy, phytochemistry and pharmacological profile. Phytomedicine Plus. 2023;3: 100469.
Olowofolahan AO, Adeoye AO, Offor GN, Adebisi LA, Olorunsogo OO. Induction of Mitochondrial Membrane Permeability Transition Pore and Cytohrome c Release by Different Fractions of Drymaria cordata. Arch Basic Appl Med. 2015;3:135–44.
Olowofolahan AO, Olorunsogo OO. Induction of Apoptosis in Rat Liver Cells Via Caspase activation by Chloroform Fraction of Methanol Extract of Drymaria cordata. Eur J Biomed Pharm Sci. 2018;5(4):73–83.
Karthikeyan A, Shanthi V, Nagasathaya A. Preliminary phytochemical and antibacterial screening of crude extract of the leaf of Adhatoda vasica. L’. Int J Green Pharm. 2009;3(1):78–80.
Bhattacharyya R. Phytochemical analysis of Drymaria cordata (L.) Willd. ex Schult. (whole plant) used by tea tribes of erstwhile Nagaon district of Assam, India. Int J Pharm Sci Res. 2019;10(9):4264–9.
Singla S, Pradhan J, Thakur R, Goyal S. Drymaria cordata: review on its pharmaconosy, phytochemistry and pharmacological profile. Phytomedicine Plus. 2023;3(3): 100469.
Olowofolahan AO, Aina OO, Hassan ET, Olorunsogo OO. Ameliorative potentials of methanol extract and chloroform fraction of Drymaria cordata on MSG-induced uterine hyperplasia in female wistar rats. Eur J Med Plants. 2017;20(4):1–9.
Kafali H, Iriadam M, Ozardalı I, Demir N. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res. 2004;35(2):103–8.
Ndeingang EC, DefoDeeh PB, Watcho P, Kamanyi A. Phyllanthus muellerianus (Euphorbiaceae) restores ovarian functions in letrozole-induced polycystic ovarian syndrome in rats. Evid Based Complement Alternat Med. 2019;2019:1–16.
Johnson D, Lardy H. Isolation of liver or kidney mitochondria. Methods Enzym. 1967;10:94–6.
Olorunsogo OO, Bababunmi EA, Bassir O. Uncoupling effect of N – phosphonomethyl glycine on rat liver mitochondria. Biochem Pharm. 1979;27:925–7.
Lowry OH, Rosebrough NJ, Farr AI, Randall RJ. Protein measurements with the folin-phenol reagent. J Biol Chem. 1951;193:260–5.
Lapidus RG, Sokolove PM. Inhibition by spermine of the inner membrane permeability transition of isolated heart mitochondria. FEBS Lett. 1993;3:314–8.
Franks S. Polycystic ovary syndrome. N Engl J Med. 1995;333(13):853–61.
Mobeen H, Afzal N, Kashif M. Polycystic Ovary Syndrome May Be an Autoimmune Disorder. Scientifica. 2016;1:1–7.
Abtahi-Eivari SH, Moghimian M, Soltani M, et al. effect of Galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome. Int J Women’s Health Reprod Sci. 2017;6(3):276–82.
Younas A, Hussain L, Shabbir A, Asif M, Hussain M, Manzoor F. Effects of Fagonia indica on letrozole-induced polycystic ovarian syndrome (PCOS) in young adult female rats. Evid-Based Complement Alternat Med. 2022;2022. https://doi.org/10.1155/2022/1397060.
Sulaiman MA, Al-Farsi YM, Al-Khaduri MM, Saleh J, Waly MI. Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women. Int J Women’s Health. 2018;10:763–71.
Gomathi D, Kalaiselvi M, Ravikumar G, Devaki K, Uma C. GC-MS analysis of bioactive compounds from the whole plant ethanolic extract of Evolvulus alsinoides(L.) L. J Food Sci Technol. 2015;52:1212–7.
Vijisaral ED, Subramanian A. GC-MS analysis of ethanol extract of Cyperus rotundus leaves. Int J Curr Biotechnol. 2014;2:19–23.
Rajeswari G, Murugan M, Mohan VR. GC-MS analysis of bioactive components of Hugonia mystax L (Linaceae). Res J Pharmaceut Bio Chem Sci. 2012;3:301–8.
Ryu KR, Choi YJ, Chung S, Kim DH. Antiscratching behavioral effect of the essential oil and phytol isolated from Artemisia princeps Pamp. In mice. Planta Med. 2011;77:22–6.
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Conceptualization: A.O.Olowofolahan.
Data curation, Formal analysis, Investigation, Methodology, Project administration: A.O.Olowofolahan and J.O.Olanlokun.
Supervision: O.O.Olorunsogo.
Validation: O.O.Olorunsogo.
Writing—original draft; Writing—review & editing: A.O.Olowofolahan.
All the authors read and approved the final manuscript.
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Olowofolahan, A.O., Olanlokun, J.O. & Olorunsogo, O.O. Protective Potential of Methanol Extract of Drymaria cordata Willd. ex Schult (MEDC) on Letrozole-Induced Polycystic Ovary Syndrome Via Modulation of Apoptotic Markers, Sex Hormones and Antioxidant Status in Rat Model. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01597-6
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DOI: https://doi.org/10.1007/s43032-024-01597-6