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Effect of Parquetina nigrescens (Afzel.) Leaves on Letrozole-Induced PCOS in Rats: a Molecular Insight into Its Phytoconstituents

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Abstract

Polycystic ovarian syndrome (PCOS) is one of the common causes of female infertility in women of reproductive age. P. nigrescens is a plant used in the treatment of various diseases including menstrual disorders. This study investigated the effect of ethanolic extracts of P. nigrescens leaves on the estrous cycle, fasting blood glucose, and hormonal and lipid profile in letrozole-induced PCOS rats and also evaluated the molecular mechanism of the active constituents using computational methods. After the induction of PCOS with letrozole, rats were treated orally for 14 days with distilled water (1 mg/kg/day), clomiphene citrate (2 mg/kg/day), metformin (7.14 mg/kg/day), and ethanolic extract of P. nigrescens (50 and 100 mg). Thereafter, selected biochemical parameters were assayed to determine the extract’s effect on the estrous cycle. Molecular docking and molecular dynamics simulation (MDS) were carried out to determine the binding affinity and relative stability of the ligand-receptor complexes. Letrozole-induced PCOS rats showed irregular estrous cyclicity, elevated (p > 0.05) triglycerides, low-density lipoprotein cholesterol (LDL), total cholesterol, insulin, testosterone, and luteinizing hormone (LH) concentration, low (p > 0.05) progesterone, low follicle-stimulating hormone (FSH), high-density lipoprotein cholesterol (HDL), and high fasting blood glucose concentration compared to that of the control group. The reproductive, biochemical, and structural alterations were reversed by the administration of ethanolic extract of P. nigrescens leaves (50 mg/kg) which restored the estrous cycle after 14 days of treatment. However, the ethanolic extracts of P. nigrescens (100 mg/kg) significantly increased (p > 0.05) FSH, HDL, and progesterone concentrations but decreased the LH, progesterone, and total cholesterol. Of all 44 compounds identified in GCMS analysis of an ethanolic extract of P. nigrescens leaves, only 2-ethylbutyl heptyl ester (CID 91705405) had a higher binding affinity for hormonal receptors and enzymes responsible for hepatic gluconeogenesis compared to standard drugs used in the study. CID 91705405 was also relatively stable over 100 ns of MDS. This compound is therefore revealed to have the potential to modulate both endocrine and metabolic pathways involved in PCOS. The ethanolic extract of P. nigrescens leaves can therefore be considered in the management/treatment of the reproductive and metabolic disorders related to PCOS subject to further experimental validation.

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Data Availability

Data obtained are presented in this manuscript.

Abbreviations

EEPNL:

Ethanolic extract of P. nigrescens leaves

FSH:

Follicle stimulating hormone

HDL:

High-density lipoprotein

LDL:

Low-density lipoprotein

LH:

Luteinizing hormone

PCOS:

Polycystic ovarian syndrome

ns:

Nanosecond

P. nigrescens :

Parquetina nigrescens

References

  1. Mikhael, S., Punjala-Patel, A., & Gavrilova-Jordan, L. (2019). Hypothalamic-pituitary-ovarian axis disorders impacting female fertility. Biomedicines, 7(1), 5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Emamalipour, M., Seidi, K., Jahanban-Esfahlan, A., & Jahanban-Esfahlan, R. (2019). Implications of resistin in type 2 diabetes mellitus and coronary artery disease: Impairing insulin function and inducing pro-inflammatory cytokines. Journal of cellular physiology, 234(12), 21758–21769.

    Article  CAS  PubMed  Google Scholar 

  3. Baskind, N. E., & Balen, A. H. (2016). Hypothalamic–pituitary, ovarian and adrenal contributions to polycystic ovary syndrome. Best Practice & Research Clinical Obstetrics & Gynaecology, 37, 80–97.

    Article  Google Scholar 

  4. Rose, B. I., & Brown, S. E. (2020). A review of the physiology behind letrozole applications in infertility: Are current protocols optimal? Journal of Assisted Reproduction and Genetics, 37(9), 2093–2104.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ndeingang, E. C., Defo Deeh, P. B., Watcho, P., & Kamanyi, A. (2019). Phyllanthus muellerianus (Euphorbiaceae) restores ovarian functions in letrozole-induced polycystic ovarian syndrome in rats. Evidence-Based Complementary and Alternative Medicine, 2019, 2965821.

  6. Auta, T., & Hassan, A. T. (2016). Alteration in oestrus cycle and implantation in Mus musculus administered aqueous wood ash extract of Azadirachta indica (neem). Asian Pacific Journal of Reproduction, 5(3), 188–192. https://doi.org/10.1016/j.apjr.2016.03.003

    Article  Google Scholar 

  7. Lim, S. S., Hutchison, S. K., Van Ryswyk, E., Norman, R. J., Teede, H. J., & Moran, L. J. (2019). Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, 3, CD007506J.

  8. Dasari, P., & Pranahita, G. K. (2009). The efficacy of metformin and clomiphene citrate combination compared with clomiphene citrate alone for ovulation induction in infertile patients with PCOS. Journal of Human Reproductive Sciences, 2(1), 18.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ajdary, M., Keyhanfar, F., Aflatoonian, R., Amani, A., Amjadi, F., Zandieh, Z., & Mehdizadeh, M. (2020). Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium. DARU Journal of Pharmaceutical Sciences, 28(2), 423–432.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Li, S., Odedina, S., Agwai, I., Ojengbede, O., Huo, D., & Olopade, O. I. (2020). Traditional medicine usage among adult women in Ibadan, Nigeria: A cross-sectional study. BMC Complementary Medicine and Therapies, 20(1), 1–7.

    Article  Google Scholar 

  11. Adeyomoye, O. I., & Adewoye, E. O. (2018). Preliminary assessments and renoprotective effects of methanol extract of Parquetina nigrescens (African Parquetina) in diabetic Wistar rats. Asian Journal of Research in Medical and Pharmaceutical Sciences, 3(4), 1–10.

    Article  Google Scholar 

  12. Kola-Mustapha, A. T., Ghazali, Y. O., Ayotunde, H. T., Atunwa, S. A., & Usman, S. O. (2019). Evaluation of the antidiarrheal activity of the leaf extract of Parquetina nigrescens and formulation into oral suspensions. Journal of Experimental Pharmacology, 11, 65.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Aborisade, A. B., Adetutu, A., & Owoade, A. O. (2017). Phytochemical and proximate analysis of some medicinal leaves. Clinical Medicine Research, 6(6), 209–214.

    Article  Google Scholar 

  14. Airaodion, A. I., Olatoyinbo, P. O., Ogbuagu, U., Ogbuagu, E. O., Akinmolayan, J. D., Adekale, O. A., … Obajimi, O. O. (2019). Comparative assessment of phytochemical content and antioxidant potential of Azadirachta indica and Parquetina nigrescens leaves. Asian Plant Research Journal, 2(3), 1–14.

  15. Femi-olabisi, F. J., Faokunla, O., Agboola, A. O., & Olorunyolemi, I. M. (2020). Biochemical and toxicological evaluations of aqueous extract of Parquetina nigrescens (Afzel.) leaves on mifepristone-induced polycystic ovarian syndrome in rats. Journal of Drug Delivery and Therapeutics, 10(2-s), 94–101.

  16. Alwan, S. H., & Al-Saeed, M. H. (2021). Biosynthesized silver nanoparticles (using Cinnamomum zeylanicum bark extract) improve the fertility status of rats with polycystic ovarian syndrome. Biocatalysis and Agricultural Biotechnology, 38, 102217.

    Article  CAS  Google Scholar 

  17. Tietz, N. W. (1995). Clinical guide to laboratory tests (3rd edn, vol. 3, pp. 1096-1096). Philadelphia: WB Saunders.

  18. O’Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An Open chemical toolbox. Journal of Cheminformatics, 3(10), 33. https://doi.org/10.1186/1758-2946-3-33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lindahl, Abraham, Hess, & Spoel, van der. (2021). GROMACS 2020.5 Source code, 1(6). https://doi.org/10.5281/ZENODO.4420785

  21. Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeerschd, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4(1), 1–17. https://doi.org/10.1186/1758-2946-4-17

    Article  CAS  Google Scholar 

  22. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., … Mackerell Jr, A. D. (2009). CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry, 31(4), 671–690.

  23. Kumari, R., Kumar, R., Consortium, O. S. D. D., & Lynn, A. (2014). g _ mmpbsa - A GROMACS tool for MM-PBSA and its optimization for high-throughput binding energy calculations. J. Chem. Inf. Model., 54(7), 1951–1962. https://doi.org/10.1021/ci500020m

  24. Hamza, A. H., AlBishri, W. M., & Alfaris, M. H. (2019). Effect of Vitex agnus-castus plant extract on polycystic ovary syndrome complications in experimental rat model. Asian Pacific Journal of Reproduction, 8(2), 63.

    Article  CAS  Google Scholar 

  25. Ajayi, A. F., & Akhigbe, R. E. (2020). Staging of the estrous cycle and induction of estrus in experimental rodents: An update. Fertility research and practice, 6(1), 1–15.

    Article  Google Scholar 

  26. Nallathambi, A., & Bhargavan, R. (2019). Regulation of estrous cycle by Cynodon dactylon in letrozole induced polycystic ovarian syndrome in Wistars albino rats. Anatomy & Cell Biology, 52(4), 511–517.

    Article  Google Scholar 

  27. Kumar, T. R., Wang, Y., Lu, N., & Matzuk, M. M. (1997). Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nature genetics, 15(2), 201–204.

    Article  CAS  PubMed  Google Scholar 

  28. Pasquali, R. (2006). Obesity and androgens: Facts and perspectives. Fertility and sterility, 85(5), 1319–1340.

    Article  CAS  PubMed  Google Scholar 

  29. Nabiuni, M., Nasri, S., Poyanmanesh, F., Karimzadeh, L., & Nazari, Z. (2012). Honey bee venom modulates hyperglycemia in response to hyperandrogenism in polycystic ovarian syndrome-induced Wistar rats. In International Conference on Applied Life Sciences. IntechOpen. https://doi.org/10.5772/intechopen.84084

  30. Moghetti, P. (2006). Use of antiandrogens as therapy for women with polycystic ovary syndrome. Fertility and sterility, 86, S30–S31.

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez Paris, V., & Bertoldo, M. J. (2019). The mechanism of androgen actions in PCOS etiology. Medical sciences, 7(9), 89.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Harwood, K., Vuguin, P., & DiMartino-Nardi, J. (2007). Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Hormone Research in Paediatrics, 68(5), 209–217.

    Article  CAS  Google Scholar 

  33. Escobar-Morreale, H. F. (2018). Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nature Reviews Endocrinology, 14(5), 270–284.

    Article  PubMed  Google Scholar 

  34. Conway, G., Dewailly, D., Diamanti-Kandarakis, E., Escobar-Morreale, H. F., Franks, S., Gambineri, A., … Pasquali, R. (2014). The polycystic ovary syndrome: A position statement from the European Society of Endocrinology. European journal of endocrinology, 171(4), P1–P29.

  35. Xu, X.-L., Deng, S.-L., Lian, Z.-X., & Yu, K. (2021). Estrogen receptors in polycystic ovary syndrome. Cells, 10(2), 459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nilsson, S., & Koehler, K. F. (2005). Oestrogen receptors and selective oestrogen receptor modulators: Molecular and cellular pharmacology. Basic & clinical pharmacology & toxicology, 96(1), 15–25.

    Article  CAS  Google Scholar 

  37. Wallach, E. E., & Adashi, E. Y. (1984). Clomiphene citrate: mechanism (s) and site (s) of action—a hypothesis revisited. Fertility and sterility, 42(3), 331–344.

  38. Lashen, H. (2010). Role of metformin in the management of polycystic ovary syndrome. Therapeutic advances in endocrinology and metabolism, 1(3), 117–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Duleba, A. J. (2012). Medical management of metabolic dysfunction in PCOS. Steroids, 77(4), 306–311.

    Article  CAS  PubMed  Google Scholar 

  40. Femi-Olabisi, F. J., Ishola, A. A., Faokunla, O., Agboola, A. O., & Babalola, B. A. (2021). Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: An in silico study. Journal of Genetic Engineering and Biotechnology, 19(1), 1–9.

    Article  Google Scholar 

  41. Mvondo, M. A., MzemdemTsoplfack, F. I., Awounfack, C. F., & Njamen, D. (2020). The leaf aqueous extract of Myrianthus arboreus P. Beauv.(Cecropiaceae) improved letrozole-induced polycystic ovarian syndrome associated conditions and infertility in female Wistar rats. BMC Complementary Medicine and Therapies, 20(1), 1–13.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, College of Basic & Applied Sciences, Mountain Top University, Makogi Oba, Ogun State, Nigeria

    Joy Fehintoluwa Femi-Olabisi & Folakemi Omolara Olujimi

  2. Central Research Laboratory, 132B, University Road, Tanke, Ilorin, Kwara State, Nigeria

    Ahmed Adebayo Ishola

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  1. Joy Fehintoluwa Femi-Olabisi
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Femi-Olabisi, J.F., Ishola, A.A. & Olujimi, F.O. Effect of Parquetina nigrescens (Afzel.) Leaves on Letrozole-Induced PCOS in Rats: a Molecular Insight into Its Phytoconstituents. Appl Biochem Biotechnol 195, 4744–4774 (2023). https://doi.org/10.1007/s12010-023-04537-3

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