Evaluating the estrogenic activity and toxicity of Tectona grandis leaf extract on the reproductive and endocrine system of female wistar rats

Authors

  • Adela Ngwewondo Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon https://orcid.org/0000-0001-9469-3618
  • Ferdinand Lanvin Edoun Ebouel Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Théodora Kopa Kowa Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Lauve Rachel Tchokouaha Yamthe Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Stephanie Guetchueng Tamdem Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Armelle Tchamgoue Deutou Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Protus Arrey Tarkang Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon
  • Bruno Lenta Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P.O. Box 47, Yaoundé, Cameroon
  • Gabriel Agbor Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Abstract

Female reproductive complications continue to be a major health challenge worldwide. Medicinal plants richer in secondary metabolites such as phytoestrogens have been used over decades for the treatment of reproductive health problems like infertility, with limited knowledge on their toxicities. The present study was designed to evaluate the estrogenic potential and safety of Tectona grandis leaves extract on female wistar rats.

Following acclimatization and pre-evaluation of the estrous cycle, female wistar rats, 6 weeks old were placed in groups of 3 animals each and T. grandis extracts administered daily in graded doses of 500, 1000, 2000mg/Kg body weight against controls for 28 days (Sub-acute toxicity). A dose dependent increase in 17-Beta estradiol was observed in the serum and ovary homogenates versus an increase in cholesterol when compared to the control groups. Results from the three animals per group showed an increase in the weights of the animals and a non-significant increase in alanine aminotransferase (ALT), white blood cells, haemoglobin and haematocrit at the dose of 2000 mg/kg. Also, there was no significant difference in the organ weights and histopathological examinations of necropsied animals showed no abnormalities in the various organs. T. grandis leave extract contains phytochemicals such as lignans that can be converted by microflora to phytoestrogens, which can compete with endogenous estrogen for the estrogen receptor potentiating similar activities like estrogens. This indicates that T. grandis could be explored as hormonal replacement therapies in infertility, menopausal and/or breast cancer related problems.

Keywords: 17-β-estradiol, Tectona grandis, lignans, phytoestrogens, toxicity, hormonal replacement therapy

Keywords:

Tectona grandis, 17-β-estradiol, lignans, phytoestrogens, toxicity, hormonal replacement therapy

DOI

https://doi.org/10.22270/jddt.v14i12.6920

Author Biographies

Adela Ngwewondo, Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Ferdinand Lanvin Edoun Ebouel , Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Théodora Kopa Kowa , Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Lauve Rachel Tchokouaha Yamthe, Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Stephanie Guetchueng Tamdem , Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Armelle Tchamgoue Deutou , Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Protus Arrey Tarkang , Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Bruno Lenta , Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P.O. Box 47, Yaoundé, Cameroon

Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P.O. Box 47, Yaoundé, Cameroon

Gabriel Agbor, Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

Institute of Medical Research and Medicinal Plants Studies, P.O Box 13033, Yaoundé, Cameroon

References

1. Telefo PB, Moundipa PF, Tchana AF, Tchouanguep DC, Mbiapo FT. Effects of aqueous extract of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus, and Justicia insularis on some biochemical and physiological parameters of reproduction in immature female rat. J Ethnopharmacol. 1998;63:193-200. https://doi.org/10.1016/S0378-8741(98)00062-2 PMid:10030723

2. Telefo PB, Moundipa PF, Tchouanguep FM. Inductive effects of the leaf mixture extract of Aloe buettneri, Justicia insularis, Dicliptera verticillata and Hibicus macranthus on in vitro production of oestradiol. J Ethnopharmacol. 2004; 90:225-30. https://doi.org/10.1016/j.jep.2003.12.024 PMid:15120443

3. Leal L, Nobre JHV, Cunha GMA, Moraes MO, Pessoa C, Oliveira RA, et al. Amburoside A, a glucoside from Amburana cearensis, protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity. Neurosci Lett. 2005;388:86-90. https://doi.org/10.1016/j.neulet.2005.06.034 PMid:16039060

4. Jha U, Asad M, Asdaq BMS, Das KA, Satya PSV. Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats. J Ethnopharmacol. 2010;127:561-4. https://doi.org/10.1016/j.jep.2009.10.021 PMid:19857563

5. Moundipa FP, Kamtchouing P, Koueta N, Mbiapo F, Tantchou J. Effects of aqueous extract of Hibiscus macranthus and Basela alba Linn. Immature rat testis function. Andrology in the nineties. In: International symposium on male infertility and assisted reproduction. 1993. p. 21-4.

6. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr. 1997;17:353-81. https://doi.org/10.1146/annurev.nutr.17.1.353 PMid:9240932

7. Louppe D, Oteng-Amoako AA, Brink M. 2008. Plant resources of Tropical Africa 7 (1). Timbers 1. Wageningen (Netherlands): PROTA Foundation.

8. Kopa TK, Tchinda AT, Tala MF, Zofou D, Jumbam R, Wabo HK, Titanji VPK, Frédérich M, Hua TN, Pierre T. 2014. Antiplasmodial anthraquinones and hemisynthetic derivatives from the leaves of Tectona grandis (Verbenaceae). Phytochem Lett. 8:41-45. https://doi.org/10.1016/j.phytol.2014.01.010

9. Gupta KP, Singh P. 2004. A naphthoquinone derivative from Tectona grandis Linn. J Asian Nat Prod Res. 6:237-240. https://doi.org/10.1080/10286020310001653192 PMid:15224424

10. Macias FA, Lacret R, Varela RM, Nogueiras C, Molinillo JMG. 2008. Bioactive apocarotenoids from Tectona grandis. Phytochemistry. 69:2708-2715. https://doi.org/10.1016/j.phytochem.2008.08.018 PMid:18834604

11. Lacret R, Varela RM, Molinillo JMG, Nogueiras C, Macias FA. 2012. Tectonoelins, new norlignans from a bioactive extract of Tectona grandis. Phytochem Lett. 5:382-386 https://doi.org/10.1016/j.phytol.2012.03.008

12. Ciocca DR, Roig LM. Estrogen receptors in human nontarget tissues: biological and clinical implications. Endocr Rev. 1995 Feb;16(1):35-62. doi: 10.1210/edrv-16-1-35. https://doi.org/10.1210/edrv-16-1-35 PMid:7758432

13. Davis, S.R., Baber, R.J. Treating menopause - MHT and beyond. Nat Rev Endocrinol 18, 490-502 (2022). https://doi.org/10.1038/s41574-022-00685-4 PMid:35624141

14. Purushotham KG, Arun P, Jayarani JJ, Vasnthakumari R, Sankar L, Bijjam RR. 2010. Synergistic in vitro antibacterial activity of Tectona grandis leaves with tetracycline. Int J Pharm Tech Res. 2(1):519-523.

15. OECD, Test No. 421: Reproduction/Developmental Toxicity Screening Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264264380-en (2016). https://doi.org/10.1787/9789264264380-en

16. OECD, "Test No. 407: repeated dose 28-day oral toxicity study in rodents," in OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects, OECD Publishing, Paris, France, (2008). https://doi.org/10.1787/9789264070684-en

17. Kamsu GT, Djamen Chuisseu DP, Fodouop Chegaing SP, Laure Feudjio HB, Ndel Famen LC, Kodjio N, Sokoudjou JB, Gatsing D. Toxicological Profile of the Aqueous Extract of Tectona grandis L.F. (Verbenaceae) Leaves: A Medicinal Plant Used in the Treatment of Typhoid Fever in Traditional Cameroonian Medicine. J Toxicol. 2021 Apr 5;2021:6646771. https://doi.org/10.1155/2021/6646771PMid:33880119 PMCid:PMC8046569

18. Auta T, Hassan AT. Alteration in oestrus cycle and implantation in Mus musculus administered aqueous wood ash extract of Azadirachta indica (neem). Asian Pacific J Reproduction. 2016;5(3):188-92. https://doi.org/10.1016/j.apjr.2016.03.003

19. Champlin AK, Dorr DL, Gates AH. Determining the stage of the estrous cycle in the mouse by the appearance of the vagina. Biol Reprod. 1973; 8(4):491-4. https://doi.org/10.1093/biolreprod/8.4.491 PMid:4736343

20. Pluskal, T., Castillo, S., Villar-Briones, A. & Oresic, M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profle data. BMC Bioinformatics. 2010 ; 11, 395 https://doi.org/10.1186/1471-2105-11-395 PMid:20650010 PMCid:PMC2918584

21. Erdtman et al. 1979 phytochemistry 1979, 18, 1945-1500 https://doi.org/10.1016/S0031-9422(00)98482-6

22. Ronald et al. 1989 phytochemistry 1989, 10, 2799-2801

23. Harill et al. 2024 Toxicological sciences 202, 103-122 https://doi.org/10.1093/toxsci/kfae108 PMid:39177380

24. Cora MC, Kooistra L, Travlos G. Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears. Toxicol Pathol. 2015;43:776-93. https://doi.org/10.1177/0192623315570339 PMid:25739587 PMCid:PMC11504324

25. Byers SL, Wiles MV, Dunn SL, Taft RA. Mouse estrous cycle identification tool and images. PLoS One. 2012;7(4):e35538. https://doi.org/10.1371/journal.pone.0035538 PMid:22514749 PMCid:PMC3325956

26. Vyas P., Yadav D.K., Khandelwal P. Tectona grandis (teak) - A review on its phytochemical and therapeutic potential. Nat Prod Res. 33(2019):2338-2354. https://doi.org/10.1080/14786419.2018.1440217 PMid:29506390

27. Asdaq S.M.B., Nayeem N., Abida, M.T. Alam, S.I. Alaqel, M. Imran, E.E. Hassan, S.I. Rabbani. Tectona grandis L.f: A comprehensive review on its patents, chemical constituents, and biological activities. Saudi J Biol Sci 2022 (29):1456-1464. https://doi.org/10.1016/j.sjbs.2021.11.026 PMid:35280534 PMCid:PMC8913375

28. Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F. Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids. 2014; 90:13-29. https://doi.org/10.1016/j.steroids.2014.06.012 PMid:24971815 PMCid:PMC4192010

29. Rietjens IM, Sotoca AM, Vervoort J, Louisse J. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks. Molecular nutrition & food research. 2013; 57(1):100-13. https://doi.org/10.1002/mnfr.201200439 PMid:23175102

30. Poluzzi E, Piccinni C, Raschi E, Rampa A, Recanatini M, De Ponti F. Phytoestrogens in postmenopause: the state of the art from a chemical, pharmacological and regulatory perspective. Current medicinal chemistry. 2014; 21(4):417-36. https://doi.org/10.2174/09298673113206660297 PMid:24164197 PMCid:PMC3963458

31. Adlercreutz H. 2002. Phyto-oestrogens and cancer. Lancet Oncol. 3:364-73). https://doi.org/10.1016/S1470-2045(02)00777-5 PMid:12107024

32. Domínguez-López I, Yago-Aragón M, Salas-Huetos A, Tresserra-Rimbau A, Hurtado-Barroso S. Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review. Nutrients. 2020 Aug 15;12(8):2456. https://doi.org/10.3390/nu12082456 PMid:32824177 PMCid:PMC7468963

33. BM Cavanaugh. Nurse's Manual of Laboratory and Diagnostics Tests. 4th Ed. F. A. Davis Company, Philadelphia. 2003; 688pp.

Published

15-12-2024
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How to Cite

1.
Ngwewondo A, Ebouel FLE, Kowa TK, Yamthe LRT, Tamdem SG, Deutou AT, et al. Evaluating the estrogenic activity and toxicity of Tectona grandis leaf extract on the reproductive and endocrine system of female wistar rats. J. Drug Delivery Ther. [Internet]. 2024 Dec. 15 [cited 2025 May 16];14(12):73-84. Available from: https://www.jddtonline.info/index.php/jddt/article/view/6920

Issue

Vol. 14 No. 12 (2024): Volume 14, Issue 12, December 2024

Section

Research

Copyright (c) 2024 Adela Ngwewondo, Ferdinand Lanvin Edoun Ebouel , Théodora Kopa Kowa , Lauve Rachel Tchokouaha Yamthe, Stephanie Guetchueng Tamdem , Armelle Tchamgoue Deutou , Protus Arrey Tarkang , Bruno Lenta , Gabriel Agbor

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How to Cite

1.
Ngwewondo A, Ebouel FLE, Kowa TK, Yamthe LRT, Tamdem SG, Deutou AT, et al. Evaluating the estrogenic activity and toxicity of Tectona grandis leaf extract on the reproductive and endocrine system of female wistar rats. J. Drug Delivery Ther. [Internet]. 2024 Dec. 15 [cited 2025 May 16];14(12):73-84. Available from: https://www.jddtonline.info/index.php/jddt/article/view/6920
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