FORMONONETIN AS PROMISING THERAPEUTIC INTERVENTION FOR RESTORING OVARIAN, UTERINE, AND HEPATO-RENAL FUNCTIONS IN LETROZOLE-INDUCED,POLYCYSTIC OVARIAN SYNDROME SPRAGUE DAWLEY RATS

Main Article Content

Ghazala Waris
Asma Ahmed
Atoofa Rukhsar
Fatima-tu-Zahra
Areesha Malik

Keywords

Polycystic ovarian syndrome, Letrozole, Cyproterone acetate, Formononetin, Ovarian, Uterine, Hepato-renal

Abstract

Polycystic ovarian syndrome is an emerging health problem for females belonging to reproductive age across the globe. Conventional methods of treatment only provide symptomatic relief with many side effects. So to seek alternative treatment options, current study was designed to observe and compare the restorative and protective roles of formononetin (40 mg/Kg.b.w./day) on ovary, uterus, liver and kidneys of PCOS induced (via letrozole @ 1.0 mg/Kg b.w./day) female Sprague dawley rats (150-200 gm) by keeping cyproterone acetate (1.0 mg/Kg.b.w./day) as positive control. Statistically analyzed results (p<0.0001) showed that after treatment of PCOS induced rats with formononetin, there was remarkable restoration of FSH, estradiol and progesterone (3.14±0.98 ml U/mL, 5.8±1.2 pg/dL and 45± 0.01 pg/mL respectively) as compared to positive control (2.5±0.01 mlU/mL, 3.05±0.3 pg/dL and 48±5.2 pg/mL respectively) while there was decrease in the levels of bilirubin and uric acid (0.4±0.01 mg/dL and 2.3±0.7 mg/dL) as compared to positive control (0.9±0.01 mg/dL and 4.7±0.15 mg/dL) respectively. Serum ALT, AST, ALP, urea and creatinine were (67±0.01 IU/L, 255±0.3 IU/L, 315±0.0I IU/L, 41.3±1.5 mg/dL, 1.31±0.25 mg/dL) in experimental group as compared to control  (78.3±1.8 IU/L, 134.3±4.5 IU/L, 618±0.0I IU/L, 55±0.01 mg/dL,0.8±0.1 mg/d) respectively.  Histological examination experimental group showed restoration of normal ovarian stroma from typical pearl string cystic appearance, with normal hepato-renal tissues. So it is concluded that formononetin may helpful to cure or mange PCOS but more studies are require to establish hepto-renal safety.

Abstract 260 | pdf Downloads 100

References

1. Bulsara J, Patel P, Soni A, Acharya S. A review: Brief insight into Polycystic Ovarian syndrome. Endocrine and Metabolic Science. 2021 Jun 30; 3:100085.
2. Witchel SF, Oberfield SE, Peña AS. Polycystic ovary syndrome: pathophysiology, presentation, and treatment with emphasis on adolescent girls. Journal of the Endocrine Society. 2019 Aug;3(8):1545-73.
3. Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ, Yildiz BO. Polycystic ovary syndrome. Nature reviews Disease primers. 2016 Aug 11;2(1):1-8.
4. Anderson RA, McLaughlin M, Wallace WH, Albertini DF, Telfer EE. The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence. Human Reproduction. 2014 Jan 1;29(1):97-106
5. Witchel SF, Oberfield SE, Peña AS. Polycystic ovary syndrome: pathophysiology, presentation, and treatment with emphasis on adolescent girls. Journal of the Endocrine Society. 2019 Aug; 3(8):1545-73.
6. Jelodar G, Askari K. Effect of Vitexagnus-castus fruits hydroalcoholic extract on sex hormones in rat with induced polycystic ovary syndrome (PCOS). Physiology and Pharmacology. 2012 Apr 10; 16(1):62-9.
7. Joshi M, Shankar R, Pathak K, Yadav R. Polycystic ovarian syndrome: A review covering phytoconstituents for its outstrip management. Pharmacological Research-Modern Chinese Medicine. 2021 Dec 1; 1:100011.
8. Ponmurugan P, Kavitha S, Suganya M, Gnanamangai BM. Tea polyphenols chemistry for pharmaceutical applications. Tea Chem. Pharmacol. 2019 Jun 3; 1:1.
9. Alkalby J, Hamzah F. Ameliorative effect of fenugreek on sex hormones in polycystic ovary syndrome female rats induced by letrozole. Kufa Journal for Veterinary Medical Sciences. 2017;8(2)..
10. Arya M, Gupta S, Dixit VP. Effect of cyproterone acetate on the reproductive system of the female ratA histological review. Actaanatomica. 1979 Mar 1;103(3):259-65.
11. Ong SK, Shanmugam MK, Fan L, Fraser SE, Arfuso F, Ahn KS, Sethi G, Bishayee A. Focus on formononetin: anticancer potential and molecular targets. Cancers. 2019 May 1;11(5):611.
12. Ajayi AF, Akhigbe RE. Staging of the estrous cycle and induction of estrus in experimental rodents: an update. Fertility research and practice. 2020 Dec;6(1):1-5.
13. Elmlinger MW. Laboratory measurements of hormones and related biomarkers: technologies, quality management and validation. Diagnostics of endocrine function in children and adolescents. Basel: Karger Publications. 2011:1-31.
14. Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, Stener-Victorin E, Fauser BC, Norman RJ, Teede H. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Human reproduction update. 2016 Nov 20;22(6):687-708.
15. Jonard S, Dewailly D. The follicular excess in polycystic ovaries, due to intra‐ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Human reproduction update. 2004 Mar 1;10(2):107-17.
16. Pasquali R. Contemporary approaches to the management of polycystic ovary syndrome. Therapeutic advances in endocrinology and metabolism. 2018 Apr;9(4):123-34.
17. Papadimitriou K, Anagnostis P, Goulis DG. The challenging role of antiandrogens in the management of polycystic ovary syndrome. InPolycystic Ovary Syndrome 2022 Jan 1 (pp. 297-314). Elsevier.
18. Dutra JM, Espitia PJ, Batista RA. Formononetin: Biological effects and uses–A review. Food chemistry. 2021 Oct 15;359:129975.
19. Kaczmarczyk-Sedlak I, Wojnar W, Zych M, Ozimina-Kamińska E, Taranowicz J, Siwek A. Effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. Evidence-Based Complementary and Alternative Medicine. 2013 Oct;2013.
20. Tay KC, Tan LT, Chan CK, Hong SL, Chan KG, Yap WH, Pusparajah P, Lee LH, Goh BH. Formononetin: a review of its anticancer potentials and mechanisms. Frontiers in pharmacology. 2019 Jul 26;10:820.
21. Arentz S, Smith CA, Abbott J, Bensoussan A. Nutritional supplements and herbal medicines for women with polycystic ovary syndrome; a systematic review and meta-analysis. BMC complementary and alternative medicine. 2017 Dec;17(1):1-4.
22. Maharjan R, Nagar PS, Nampoothiri L. Effect of Aloe barbadensis Mill. formulation on Letrozole induced polycystic ovarian syndrome rat model. Journal of Ayurveda and integrative medicine. 2010 Oct;1(4):273.
23. Rajan RK, Balaji B. Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism. Pharmaceutical biology. 2017 Jan 1;55(1):242-51.
24. Gade R, Dwarampudi LP, Dharshini SP, Raj R K. Polycystic ovarian syndrome (PCOS): Approach to traditional systems, natural and bio-chemical compounds for its management. Indian Journal of Biochemistry and Biophysics (IJBB). 2022 May 30;59(5):521-7.
25. Jin F, Wan C, Li W, Yao L, Zhao H, Zou Y, Peng D, Huang W. Formononetin protects against acetaminophen-induced hepatotoxicity through enhanced NRF2 activity. PloS one. 2017 Feb 24;12(2):e0170900.
26. Oza MJ, Kulkarni YA. Formononetin treatment in type 2 diabetic rats reduces insulin resistance and hyperglycemia. Frontiers in pharmacology. 2018 Jul 18;9:739.
27. Oza MJ, Kulkarni YA. Formononetin attenuates kidney damage in type 2 diabetic rats. Life sciences. 2019 Feb 15;219:109-21.

Most read articles by the same author(s)