Home Albizia ferruginea (Guill. & Perr.) Benth. leaf abates deregulation of P53, IRS, HsD17β2, FTO, and CYP11a genes in polycystic ovarian syndrome rat
Article
Licensed
Unlicensed Requires Authentication

Albizia ferruginea (Guill. & Perr.) Benth. leaf abates deregulation of P53, IRS, HsD17β2, FTO, and CYP11a genes in polycystic ovarian syndrome rat

  • Akingbolabo Daniel Ogunlakin EMAIL logo , Meek Oyinlola Meruwoma , Princewill Obinna Ihiasota , Oluwafemi Adeleke Ojo ORCID logo , Adeyemi Abdullahi Adegoke , Idayat Adeola Akinwumi , Owoola Azeezat Ambali , Oyindamola Esther Awosola and Mubo Adeola Sonibare
Published/Copyright: November 29, 2024

Abstract

Objectives

This study investigated the potential ameliorative effects of Albizia ferruginea leaves on letrozole-induced polycystic ovarian syndrome (PCOS) in Wistar rats.

Methods

PCOS was induced in 25 female Wistar rats by administering letrozole (1 mg/kg), followed by treatment with 100 and 250 mg/kg body weight A. ferruginea leaf methanolic extract, as well as 1 mg/kg body weight of clomiphene citrate as standard.

Results

An acute toxicity study revealed a toxic dosage of 2,000 mg/kg for the plant extract. The A. ferruginea extract exhibited potent hydroxyl radical scavenging ability. Treatment with A. ferruginea leaf extract improved the irregular estrus cycle and hormonal imbalance. Additionally, the extract administration led to decreased testosterone and increased estradiol levels when compared to the untreated PCOS rat. Furthermore, methanol extract normalizes the levels of insulin receptor substrate (IRS), type 2 17-HSD (HsD17β2), P53, 11a-hydroxylase/17,20-desmolase (CYP11a), and fat mass and obesity-associated (FTO), genes in the cervix of PCOS rats.

Conclusions

Overall, A. ferruginea demonstrated beneficial properties on polycystic ovary circumstances in rats, presenting its potential as a promising treatment for PCOS.


Corresponding author: Akingbolabo Daniel Ogunlakin, Good Health and Wellbeing Research Cluster, Bowen University, Iwo 232101, Nigeria; and Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo 232101, Nigeria, E-mail:

Acknowledgments

We appreciate Bowen University for supporting this research.

  1. Research ethics: Every relevant institutional, governmental, and/or international law pertaining to the use and care of animals was adhered to. The research was also approved by the University of Ibadan Animal Care and Use Research Ethics Committee (UI-ACUREC/19/0051).

  2. Informed consent: Not applicable.

  3. Author contributions: Conceptualization: ADO; formal Analysis: all author; software: ADO, MOM and POI; funding acquisition: ADO, OAO, AAA and OEA; writing (original draft): ADO, MOM and POI; writing (review & editing): ADO; supervision: ADO.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Data will be made available on request.

References

1. Louwers, YV, Laven, JS. Characteristics of polycystic ovary syndrome throughout life. Ther Adv Reprod Health 2020;14:2633494120911038. https://doi.org/10.1177/2633494120911038.Search in Google Scholar PubMed PubMed Central

2. Ramya, S, Poornima, P, Jananisri, A, Geofferina, IP, Bavyataa, V, Divya, M, et al.. Role of hormones and the potential impact of multiple stresses on infertility. Stresses 2023;3:454–74. https://doi.org/10.3390/stresses3020033.Search in Google Scholar

3. Nicolaides, NC, Matheou, A, Vlachou, F, Neocleous, V, Skordis, N. Polycystic ovarian syndrome in adolescents: from diagnostic criteria to therapeutic management. Acta Biomed: Atenei Parmensis 2020;91:e2020085. https://doi.org/10.23750/abm.v91i3.10162.Search in Google Scholar PubMed PubMed Central

4. Omagbemi, A, Ezinne, C, Ofeoritse, A. Current knowledge and perceptions of women about polycystic ovarian syndrome in Nigeria. Int J Sci Res 2020;5.Search in Google Scholar

5. Ugwu, GO, Iyoke, CA, Onah, HE, Mba, SG. Prevalence, presentation and management of polycystic ovary syndrome in Enugu, south east Nigeria. Niger J Med 2013;22:313–6.Search in Google Scholar

6. Ogunlakin, AD, Ojo, OA, Gyebi, GA, Adebodun, GO, Elbasyouni, A, Adebodun, SA, et al.. Effect of Triclisia subcordata Oliv.(Menispermaceae) leaves on hormonal imbalance and genes expression in the ovaries of letrozole-induced polycystic rats via in vivo and computational approaches. J Mol Struct 2024;1318:139275. https://doi.org/10.1016/j.molstruc.2024.139275.Search in Google Scholar

7. Sayutti, N, Abu, MA, Ahmad, MF. PCOS and role of cumulus gene expression in assessing oocytes quality. Front Endocrinol 2022;13:843867. https://doi.org/10.3389/fendo.2022.843867.Search in Google Scholar PubMed PubMed Central

8. Vaou, N, Stavropoulou, E, Voidarou, C, Tsakris, Z, Rozos, G, Tsigalou, C, et al.. Interactions between medical plant-derived bioactive compounds: focus on antimicrobial combination effects. Antibiotics 2022;11:1014. https://doi.org/10.3390/antibiotics11081014.Search in Google Scholar PubMed PubMed Central

9. de Lima Pereira, MC, Mariano, MR, de Souza Maciel, N. Use of medicinal plants in care of women with gynecological diseases: integrative review. Int J Dev Res 2019;9:26373–80.Search in Google Scholar

10. De Boer, HJ, Cotingting, C. Medicinal plants for women’s healthcare in southeast Asia: a meta-analysis of their traditional use, chemical constituents, and pharmacology. J Ethnopharmacol 2014;151:747–67. https://doi.org/10.1016/j.jep.2013.11.030.Search in Google Scholar PubMed

11. Ashkar, F, Rezaei, S, Salahshoornezhad, S, Vahid, F, Gholamalizadeh, M, Dahka, SM, et al.. The Role of medicinal herbs in treatment of insulin resistance in patients with Polycystic Ovary Syndrome: a literature review. Biomol Concepts 2020;11:57–75. https://doi.org/10.1515/bmc-2020-0005.Search in Google Scholar PubMed

12. Ukpabi, SE, Offor, CE, Udeozor, PA, Obiudu, IK. Effects of ethanol leaf-extract of Albizia ferruginea on selected haematological indices in wistar albino rats. Int Sci Res Organ J 2018;3:74–81.Search in Google Scholar

13. Tagoe, M, Boakye, YD, Agana, TA, Boamah, VE, Agyare, C. In vitro anthelmintic activity of ethanol stem bark extract of Albizia ferruginea (Guill. & Perr.) Benth. J Parasitol Res 2021;2021:6690869. https://doi.org/10.1155/2021/6690869.Search in Google Scholar PubMed PubMed Central

14. Yusuf, AL, Abdullahi, B, Abdulaziz, I. Phytochemical screening and evaluation of antimicrobial activity of Albizia ferruginea (Fabaceae) leaves extract. Bayero J Pure Appl Sci 2021;14:189–92. https://doi.org/10.4314/bajopas.v14i1.22.Search in Google Scholar

15. Madaki, F, Kabiru, A, Mann, A, Abdulkadir, A, Agadi, J, Akinyode, AO. Phytochemical analysis and In-vitro antitrypanosomal activity of selected medicinal plants in Niger State: Nigeria.Search in Google Scholar

16. Ditchou, YN, Kombo, CA, Opono, MM, Nyasse, B. Antioxidant activity of the chemical constituents isolated from the roots of Albizia ferruginea (guill. & perr.) benth.(fabaceae). J Adv Chem Sci 2019;21:646–51.10.30799/jacs.212.19050301Search in Google Scholar

17. Brand-Williams, W, Cuvelier, ME, Berset, CL. Use of a free radical method to evaluate antioxidant activity. LWT--Food Sci Technol 1995;28:25–30. https://doi.org/10.1016/s0023-6438(95)80008-5.Search in Google Scholar

18. Halvorsen, BL, Holte, K, Myhrstad, MC, Barikmo, I, Hvattum, E, Remberg, SF, et al.. A systematic screening of total antioxidants in dietary plants. J Nutr 2002;132:461–71. https://doi.org/10.1093/jn/132.3.461.Search in Google Scholar PubMed

19. Özyürek, M, Bektaşoğlu, B, Güçlü, K, Apak, R. Hydroxyl radical scavenging assay of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method using catalase for hydrogen peroxide degradation. Anal Chim Acta 2008;616:196–206. https://doi.org/10.1016/j.aca.2008.04.033.Search in Google Scholar PubMed

20. Dinis, TC, Madeira, VM, Almeida, LM. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 1994;315:161–9. https://doi.org/10.1006/abbi.1994.1485.Search in Google Scholar PubMed

21. Ozioko, EN, Ajibade, GA, Vantsawa, PA, Appah, J, Solomon, A. Effect of letrozole and toxicity profile of five medicinal plants used in controlling parameters of polycystic ovarian syndrome in female Wistar albino rat. Int J Curr Res Med Sci. 2022;8:52–61.Search in Google Scholar

22. Ogunlakin, AD, Sonibare, MA. Antioxidant and ameliorative effects of basella alba L. On letrozole-induced polycystic ovarian syndrome in rats. Trop J Nat Prod Res 2023;7.10.26538/tjnpr/v7i4.25Search in Google Scholar

23. Ogunlakin, AD, Sonibare, MA, Jabeen, A, Shaheen, F, Shah, SF. Antiproliferative and ameliorative effects of Tetracera potatoria and its constituent. Adv Tradit Med 2021;21:815–24. https://doi.org/10.1007/s13596-020-00511-0.Search in Google Scholar

24. Elekofehinti, OO, Lawal, AO, Ejelonu, OC, Molehin, OR, Famusiwa, CD. Involvement of fat mass and obesity gene (FTO) in the anti-obesity action of Annona muricata Annonaceae: in silico and in vivo studies. J Diabetes Metab Disord 2020;19:197–204. https://doi.org/10.1007/s40200-020-00491-7.Search in Google Scholar PubMed PubMed Central

25. Olumegbon, LT, Lawal, AO, Oluyede, DM, Adebimpe, MO, Elekofehinti, OO, Umar, H. Hesperetin protects against diesel exhaust particles-induced cardiovascular oxidative stress and inflammation in Wistar rats. Environ Sci Pollut Control Ser 2022;29:52574–89. https://doi.org/10.1007/s11356-022-19494-3.Search in Google Scholar PubMed

26. Rudnicka, E, Duszewska, AM, Kucharski, M, Tyczyński, P, Smolarczyk, R. Oxidative stress and reproductive function: oxidative stress in polycystic ovary syndrome. Reproduction 2022;164:F145–54. https://doi.org/10.1530/rep-22-0152.Search in Google Scholar PubMed

27. Baliyan, S, Mukherjee, R, Priyadarshini, A, Vibhuti, A, Gupta, A, Pandey, RP, et al.. Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules 2022;27:1326. https://doi.org/10.3390/molecules27041326.Search in Google Scholar PubMed PubMed Central

28. Hayyan, M, Hashim, MA, AlNashef, IM. Superoxide ion: generation and chemical implications. Chem Rev 2016;116:3029–85. https://doi.org/10.1021/acs.chemrev.5b00407.Search in Google Scholar PubMed

29. Escobar-Morreale, HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018;14:270–84. https://doi.org/10.1038/nrendo.2018.24.Search in Google Scholar PubMed

30. Witchel, SF, Oberfield, SE, Peña, AS. Polycystic ovary syndrome: pathophysiology, presentation, and treatment with emphasis on adolescent girls. J Endocr Soc 2019;3:1545–73. https://doi.org/10.1210/js.2019-00078.Search in Google Scholar PubMed PubMed Central

31. Mvondo, MA, Mzemdem Tsoplfack, FI, Awounfack, CF, Njamen, D. 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 complement med ther 2020;20:1–3. https://doi.org/10.1186/s12906-020-03070-8.Search in Google Scholar PubMed PubMed Central

32. Mitrašinović-Brulić, M, Buljan, M, Suljević, D. Association of LH/FSH ratio with menstrual cycle regularity and clinical features of patients with polycystic ovary syndrome. Middle East Fertil Soc J 2021;26:1–9. https://doi.org/10.1186/s43043-021-00085-0.Search in Google Scholar

33. Oyebanji, OG, Asaolu, MF, Amonimo, EO. Hormonal imbalance in polycystic ovarian syndrome (PCOS) in teaching hospitals in Ekiti State, Nigeria. Open J Obstet Gynecol 2018;8:1456–64. https://doi.org/10.4236/ojog.2018.813147.Search in Google Scholar

34. Sampurna, K, Reddy, BV, Vijayaraghavan, R, Rajesh, P. Role of steroid hormones in polycystic ovarian syndrome (PCOS) in south Indian women. Int J Res Ayurveda Pharm 2017;8:234–7. https://doi.org/10.7897/2277-4343.082118.Search in Google Scholar

35. Kaur, S, Archer, KJ, Devi, MG, Kriplani, A, Strauss, IIIJF, Singh, R. Differential gene expression in granulosa cells from polycystic ovary syndrome patients with and without insulin resistance: identification of susceptibility gene sets through network analysis. J Clin Endocrinol Metabol 2012;97:E2016–21. https://doi.org/10.1210/jc.2011-3441.Search in Google Scholar PubMed PubMed Central

36. Barrett, T, Wilhite, SE, Ledoux, P, Evangelista, C, Kim, IF, Tomashevsky, M, et al.. NCBI geo: archive for functional genomics data sets—update. Nucleic Acids Res 2012;41:D991–5. https://doi.org/10.1093/nar/gks1193.Search in Google Scholar PubMed PubMed Central

37. Weizman, NF, Wyse, BA, Gat, I, Balakier, H, Sangaralingam, M, Caballero, J, et al.. Triggering method in assisted reproduction alters the cumulus cell transcriptome. Reprod Biomed Online 2019;39:211–24. https://doi.org/10.1016/j.rbmo.2019.03.213.Search in Google Scholar PubMed

38. Gharani, N, Waterworth, DM, Batty, S, White, D, Gilling-Smith, C, Conway, GS, et al.. Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Hum Mol Genet 1997;6:397–402. https://doi.org/10.1093/hmg/6.3.397.Search in Google Scholar PubMed

39. Urbanek, M, Legro, RS, Driscoll, DA, Azziz, R, Ehrmann, DA, Norman, RJ, et al.. Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA 1999, 96:8573–8. https://doi.org/10.1073/pnas.96.15.8573.Search in Google Scholar PubMed PubMed Central

40. Zanjirband, M, Rahgozar, S. Targeting p53-MDM2 interaction using small molecule inhibitors and the challenges needed to be addressed. Curr Drug Targets 2019;20:1091–111. https://doi.org/10.2174/1389450120666190402120701.Search in Google Scholar PubMed

41. Charni-Natan, M, Aloni-Grinstein, R, Osher, E, Rotter, V. Liver and steroid hormones—can a touch of p53 make a difference? Front Endocrinol 2019;10:374. https://doi.org/10.3389/fendo.2019.00374.Search in Google Scholar PubMed PubMed Central

42. Kung, CP, Murphy, ME. The role of the p53 tumor suppressor in metabolism and diabetes. J Endocrinol 2016;231:R61. https://doi.org/10.1530/joe-16-0324.Search in Google Scholar

43. Shafiee, MN, Malik, DA, Yunos, RI, Atiomo, W, Omar, MH, Ghani, NA, et al.. The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome–a proof-of-concept study. Gynecol Endocrinol 2015;31:286–90. https://doi.org/10.3109/09513590.2014.989982.Search in Google Scholar PubMed

44. Gadducci, A, Biglia, N, Tana, R, Cosio, S, Gallo, M. Metformin use and gynecological cancers: a novel treatment option emerging from drug repositioning. Crit Rev Oncol-Hematol 2016;105:73–83. https://doi.org/10.1016/j.critrevonc.2016.06.006.Search in Google Scholar PubMed

45. Ogunlakin, AD, Sonibare, MA, Yeye, OE, Gyebi, GA, Ayokunle, DI, Arigbede, OE, et al.. Isolation and characterization of novel hydroxyflavone from Kigelia africana (Lam.) Benth. fruit ethyl acetate fraction against CHO 1 and HeLa cancer cell lines: in vitro and in silico studies. J Mol Struct 2023;1282:135180. https://doi.org/10.1016/j.molstruc.2023.135180.Search in Google Scholar

46. Fawcett, KA, Barroso, I. The genetics of obesity: FTO leads the way. Trends Genet 2010;26:266–74. https://doi.org/10.1016/j.tig.2010.02.006.Search in Google Scholar PubMed PubMed Central

47. Tan, S, Scherag, A, Janssen, OE, Hahn, S, Lahner, H, Dietz, T, et al.. Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS). BMC Med Genet 2010;11:1–9. https://doi.org/10.1186/1471-2350-11-12.Search in Google Scholar PubMed PubMed Central

48. Attaoua, R, Ait El Mkadem, S, Radian, S, Fica, S, Hanzu, F, Albu, A, et al.. FTO gene associates to metabolic syndrome in women with polycystic ovary syndrome. Biochem Biophys Res Commun 2008;373:230–4. https://doi.org/10.1016/j.bbrc.2008.06.039.Search in Google Scholar PubMed

49. Kowalska, I, Malecki, MT, Straczkowski, M, Skupien, J, Karczewska-Kupczewska, M, Nikolajuk, A, et al.. The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes. Diabetes Metabol 2009;35:328–31. https://doi.org/10.1016/j.diabet.2009.03.004.Search in Google Scholar PubMed

50. Barber, TM, Bennett, AJ, Groves, CJ, Sovio, U, Ruokonen, A, Martikainen, H, et al.. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 2008;51:1153–8. https://doi.org/10.1007/s00125-008-1028-6.Search in Google Scholar PubMed

51. Yan, Q, Hong, J, Gu, W, Zhang, Y, Liu, Q, Su, Y, et al.. Association of the common rs9939609 variant of FTO gene with polycystic ovary syndrome in Chinese women. Endocrine 2009;36:377–82. https://doi.org/10.1007/s12020-009-9257-0.Search in Google Scholar PubMed

52. Hay, JB, Hodgins, MB. Distribution of androgen metabolizing enzymes in isolated tissues of human forehead and axillary skin. J Endocrinol 1978;79:29–39. https://doi.org/10.1677/joe.0.0790029.Search in Google Scholar PubMed

53. Oliveira, IO, Lhullier, C, Brum, IS, Spritzer, PM. Gene expression of type 2 17β hydroxysteroid dehydrogenase in scalp hairs of hirsute women. Steroids 2003;68:641–9. https://doi.org/10.1016/s0039-128x(03)00093-x.Search in Google Scholar PubMed

54. Ruan, Y, Ma, J, Xie, X. Association of IRS-1 and IRS-2 genes polymorphisms with polycystic ovary syndrome: a meta-analysis. Endocr J 2012;59:601–9. https://doi.org/10.1507/endocrj.ej11-0387.Search in Google Scholar PubMed

55. El Mkadem, SA, Lautier, C, Macari, F, Molinari, N, Lefebvre, P, Renard, E, et al.. Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes 2001;50:2164–8. https://doi.org/10.2337/diabetes.50.9.2164.Search in Google Scholar PubMed

56. Villuendas, G, Botella-Carretero, JI, Roldán, B, Sancho, J, Escobar-Morreale, HF, Millán, JL. Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. Hum Reprod 2005;20:3184–91. https://doi.org/10.1093/humrep/dei205.Search in Google Scholar PubMed


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jcim-2024-0287).


Received: 2024-08-27
Accepted: 2024-11-07
Published Online: 2024-11-29

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Terpene-based novel invasomes: pioneering cancer treatment strategies in traditional medicine
  4. Mind-body practices for people living with dementia and their family carers: a systematic review
  5. Methodological advances in formulation and assay of herbal resources-based topical drug delivery systems
  6. Research Articles
  7. A potential therapeutic role of resveratrol in mitigating hepatotoxicity induced by paracetamol and alcohol
  8. A preclinical study on effect of betanin on sodium fluoride induced hepatorenal toxicity in Wistar rats
  9. Phytochemical characterization and evaluation of the biological activity spectrum of ethanolic fruit extract of Garcinia indica: a less explored plant of Ayurveda
  10. Scientific investigation on antibacterial, antioxidant, cytotoxic effects and TLC bioautography of Terminalia schimperiania stem bark extracts
  11. Albizia ferruginea (Guill. & Perr.) Benth. leaf abates deregulation of P53, IRS, HsD17β2, FTO, and CYP11a genes in polycystic ovarian syndrome rat
  12. Vernonia amygdalina aqueous leaf extract modulates metformin pharmacokinetics, inhibits CYP3A4 and CYP2C9 enzymes in streptozotocin-induced diabetic rats
  13. Quantitative determination of the antibacterial activity of licorice (Glycyrrhiza glabra) and tetracycline gel against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) – a microbiological in vitro study
  14. In-silico screening of bioactive compounds of Moringa oleifera as potential inhibitors targeting HIF-1α/VEGF/GLUT-1 pathway against breast cancer
  15. Isolation, structural characterization, and molecular docking studies on the bioactive compound from n-Hexane extract of Emilia sonchifolia (L.) DC against the pancreatic cancer target Aurora 2 Kinase
  16. The impact of Omega-3 supplementation on arrhythmia reduction in acute coronary syndrome patients: a randomized clinical trial
  17. Evaluation of gastric tolerability for long-term use of diclofenac and celecoxib in male albino rats and potential gastroprotective benefits of royal jelly: a randomized controlled trial
  18. The efficacy of thread embedding acupuncture on pain score, neck disability index, and pressure pain threshold for myofascial pain therapy in the upper trapezius muscle
  19. Correction of hypoxic effects on target organs in pneumonia with phytotherapy
Downloaded on 14.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jcim-2024-0287/html
Scroll to top button