Skip to main navigation menu Skip to main content Skip to site footer
Plant Science Today (PST)

Research Articles

Early Access

Exploring the therapeutic potential of sesamol and daidzein in polycystic ovarian syndrome: An in-silico approach

DOI
https://doi.org/10.14719/pst.5591
Submitted
7 October 2024
Published
06-05-2025
Versions

Abstract

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women, characterized by hormonal imbalances, including elevated androgen levels. In the search for potential therapeutic agents, phytocompounds such as Sesamol and Daidzein have gained attention due to their antioxidant and oestrogenic properties. This study investigated the binding affinity and pharmacokinetic properties of Sesamol and Daidzein as potential treatments for PCOS through molecular docking and in silico analysis. Molecular docking studies were conducted using AutoDock Vina, targeting oestrogen receptor beta (ER?), androgen receptor (AR) and aromatase (CYP19A1) as key macromolecules involved in PCOS pathophysiology. The docking results revealed significant binding affinities, with Daidzein showing a binding energy of -8.9 kcal/mol to ER?, -5.2 kcal/mol to AR and -9.2 kcal/mol to CYP19A1. Sesamol exhibited binding energies of -5.9 kcal/mol to both ER? and AR and -5.8 kcal/mol to CYP19A1. These values, although lower than the respective endogenous ligands (Oestradiol: -11.0 kcal/mol, Testosterone: -12.0 kcal/mol and - 11.3 kcal/mol), indicate a favorable interaction with the target receptors. Additionally, pharmacokinetic properties, including absorption, distribution, metabolism, excretion and toxicity (ADMET), were analyzed using SwissADME and AdmetSAR tools. The analysis demonstrated favorable drug-likeness and ADMET profiles for both sesamol and daidzein, reinforcing their suitability as therapeutic candidates. The findings from this study suggested that sesamol and daidzein possess promising pharmacological profiles and could be considered for further in vivoand clinical studies as potential therapeutic agents for managing PCOS.

References

  1. Stener-Victorin E, Teede H, Norman RJ, Legro R, Goodarzi MO, Dokras A, et al. Polycystic ovary syndrome. Nat Rev Dis Prim. 2024;10(1):27. https://doi.org/10.1038/s41572-024-00511-3
  2. Asghari MK, Nejadghaderi SA, Alizadeh M, Sanaie S, Sullman MJ, Kolahi AA, et al. Burden of polycystic ovary syndrome in the Middle East and North Africa region, 1990–2019. Sci Rep. 2022;12(1):7039. https://doi.org/
  3. 1038/s41598-022-11006-0
  4. Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, Kumar M. Polycystic ovary syndrome: etiology, current management and future therapeutics. J Clin Med. 2023;12(4):1454. https://doi.org/10.3390/jcm12041454
  5. Bai H, Ding H, Wang M. Polycystic Ovary Syndrome (PCOS): Symptoms, Causes and Treatment. Clin Exp Obstet Gynecol. 2024;51(5):126. https://doi.org/10.31083/j.ceog5105126
  6. Roghani M, Mahdavi VMR, Jalali?Nadoushan MR, Baluchnejadmojarad T, Naderi G, Roghani?Dehkordi F, et al. Chronic administration of daidzein, a soybean isoflavone, improves endothelial dysfunction and attenuates oxidative stress in streptozotocin?induced diabetic rats. Phyther Res. 2013;27(1):112–17. https://doi.org/10.1002/ptr.4699
  7. Márquez-Flores YK, Martínez-Galero E, Correa-Basurto J, Sixto-López Y, Villegas I, Rosillo MÁ, et al. Daidzein and Equol: Ex vivo and in silico approaches targeting COX-2, iNOS and the canonical inflammasome signaling pathway. Pharmaceuticals. 2024;17(5):647. https://doi.org/10.3390/ph17050647
  8. Yashaswini PS, Rao AGA, Singh SA. Inhibition of lipoxygenase by sesamol corroborates its potential anti-inflammatory activity. Int J Biol Macromol. 2017;94:781–87. https://doi.org/10.1016/j.ijbiomac.2016.06.048
  9. Huggins DJ, Sherman W, Tidor B. Rational approaches to improving selectivity in drug design. J Med Chem. 2012;55(4):1424–44. https://doi.org/10.1021/jm2010332
  10. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2010;31(2):455–61. https://doi.org/10.1002/jcc.21334
  11. Drummond AE, Findlay JK. The role of estrogen in folliculogenesis. Mol Cell Endocrinol. 1999;151(1–2):57–64. https://doi.org/10.1016/S0303-7207(99)00038-6
  12. Xu XL, Huang ZY, Yu K, Li J, Fu XW, Deng SL. Estrogen biosynthesis and signal transduction in ovarian disease. Front Endocrinol (Lausanne). 2022;13:827032. https://doi.org/10.3389/fendo.2022.827032
  13. Yu K, Huang ZY, Xu XL, Li J, Fu XW, Deng SL. Estrogen receptor function: impact on the human endometrium. Front Endocrinol (Lausanne). 2022;13:827724. https://doi.org/10.3389/fendo.2022.827724
  14. Yang H, Lee SY, Lee SR, Pyun BJ, Kim HJ, Lee YH, et al. Therapeutic effect of Ecklonia cava extract in letrozole-induced polycystic ovary syndrome rats. Front Pharmacol. 2018;9:1325. https://doi.org/10.3389/fphar.2018.01325
  15. Xu XL, Deng SL, Lian ZX, Yu K. Estrogen receptors in polycystic ovary syndrome. Cells. 2021;10(2):459. https://doi.org/10.3390/cells10020459
  16. Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25(4):1825–37. https://doi.org/10.1111/jcmm.16205
  17. Hong Y, Li H, Yuan Y, Chen S. Molecular characterization of aromatase. Ann N Y Acad Sci. 2009;1155(1):112–20. https://doi.org/10.1111/j.1749-6632.2009.03703.x
  18. Panghiyangani R, Soeharso P, Suryandari DA, Wiweko B, Kurniati M, Pujianto DA. CYP19A1 gene expression in patients with polycystic ovarian syndrome. J Hum Reprod Sci. 2020;13(2):100–03. https://doi.org/10.4103/jhrs.JHRS_
  19. _18
  20. Narayana S, Ananad C, Kumari NS, Sonkusere S, Babu SVS. Impact of Aromatase enzyme and its altered regulation on Polycystic Ovary Syndrome (PCOS): A key factor in pathogenesis of PCOS. Indian J Med Spec. 2023;14(4):206–11. https://doi.org/10.4103/injms.injms_52_23
  21. Kandasamy V, Sathish S, Madhavan T, Balasundaram U. In-silico screening of phytochemical compounds in Caesalpinia bonducella L. seeds against the gene targets of ovarian steroidogenesis pathway. J Microbiol Biotechnol food Sci. 2023;13(2):e6124–e6124. https://doi.org/10.55251/jmbfs.6124
  22. Priyanka CL, Premkumar B. Exploring the therapeutic potential of phytoconstituents in treatment of polycystic ovarian syndrome: An in-silico study. https://doi.org/10.18231/j.ijpp.2023.020
  23. Lizcano F. Roles of estrogens, estrogen-like compounds and endocrine disruptors in adipocytes. Front Endocrinol (Lausanne). 2022;13:921504. https://doi.org/10.3389/fendo.2022.921504
  24. Khorchani MJ, Zal F, Neisy A. The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat. Reprod Fertil Dev. 2020;32(3):313–21. https://doi.org/10.1071/RD19072
  25. Deligeoroglou E, Vrachnis N, Athanasopoulos N, Iliodromiti Z, Sifakis S, Iliodromiti S, et al. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol. 2012;28(12):974–78. https://doi.org/10.3109/
  26. 2012.683082
  27. Ojeda-Ojeda M, Murri M, Insenser M, F Escobar-Morreale H. Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS). Curr Pharm Des. 2013;19(32):5775–91. https://doi.org/10.2174/1381612811319
  28. Miadoková E. Isoflavonoids—An overview of their biological activities and potential health benefits. Interdiscip Toxicol. 2009;2(4):211–18. https://doi.org/10.2478/v10102-009-0021-3
  29. Chen J, Chang H. By modulating androgen receptor coactivators, daidzein may act as a phytoandrogen. Prostate. 2007;67(5):457–62. https://doi.org/10.1002/pros.20470
  30. Singh S, Grewal S, Sharma N, Behl T, Gupta S, Anwer MK, et al. Unveiling the pharmacological and nanotechnological facets of daidzein: Present state-of-the-art and future perspectives. Molecules. 2023;28(4):1765.
  31. https://doi.org/10.3390/molecules28041765
  32. Talebi A, Hayat P, Ghanbari A, Ardekanian M, Zarbakhsh S. Sesamol protects the function and structure of rat ovaries against side effects of cyclophosphamide by decreasing oxidative stress and apoptosis. J Obstet Gynaecol Res. 2022;48(7):1786–94. https://doi.org/10.1111/jog.15315
  33. Bosebabu B, Cheruku SP, Chamallamudi MR, Nampoothiri M, Shenoy RR, Nandakumar K, et al. An appraisal of current pharmacological perspectives of sesamol: A review. Mini Rev Med Chem. 2020;20(11):988–1000. https://doi.org/10.2174/1389557520666200313120419
  34. Sachdeva AK, Misra S, Kaur IP, Chopra K. Neuroprotective potential of sesamol and its loaded solid lipid nanoparticles in ICV-STZ-induced cognitive deficits: behavioral and biochemical evidence. Eur J Pharmacol. 2015;747:132–40. https://doi.org/10.1016/j.ejphar.2014.11.014
  35. Oostenbrink BC, Pitera JW, van Lipzig MMH, Meerman JHN, van Gunsteren WF. Simulations of the estrogen receptor ligand-binding domain: affinity of natural ligands and xenoestrogens. J Med Chem. 2000;43(24):4594–605. https://doi.org/10.1021/jm001045d
  36. Pianjing P, Thiantanawat A, Rangkadilok N, Watcharasit P, Mahidol C, Satayavivad J. Estrogenic activities of sesame lignans and their metabolites on human breast cancer cells. J Agric Food Chem. 2011;59(1):212–21. https://doi.org/10.1021/jf102006w
  37. Lallous N, Dalal K, Cherkasov A, Rennie PS. Targeting alternative sites on the androgen receptor to treat castration-resistant prostate cancer. Int J Mol Sci. 2013;14(6):12496–519. https://doi.org/10.3390/ijms140612496
  38. Corpas M. Folding patterns in protein sequences. The University of Manchester (United Kingdom); 2007.
  39. Yadav V, Fuentes JL, Krishnan A, Singh N, Vohora D. Guidance for the use and interpretation of assays for monitoring anti-genotoxicity. Life Sci. 2023;122341. https://doi.org/10.1016/j.lfs.2023.122341
  40. Sun C, Zhao S, Pan Z, Li J, Wang Y, Kuang H. The role played by mitochondria in polycystic ovary syndrome. DNA Cell Biol. 2024;43(4):158–74. https://doi.org/10.1089/dna.2023.0345
  41. Ahn D, Go RE, Choi KC. Oxygen consumption rate to evaluate mitochondrial dysfunction and toxicity in cardiomyocytes. Toxicol Res. 2023;39(3):333–39. https://doi.org/10.1007/s43188-023-00183-3

Downloads

Download data is not yet available.