Effect of Annona muricata leaf ethanol extract on testosterone-induced benign prostatic hyperplasia in Wistar rats
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Abstract
Benign prostatic hyperplasia (BPH) has become the most common urological disease among aging men. This study investigated the inhibitory effect of Annona muricata leaf ethanol extract on a BPH animal model. Thirty male Wistar rats with weight range from 80-100g were divided into six groups: normal control (NC), testosterone-induced negative control (TC), Finasteride treatment control (FT), and the A. muricata low, medium, and high dose treatment groups: AML (100 mg/kg), AMM (200 mg/kg) and AMH (400 mg/kg) b.w respectively. BPH was induced by subcutaneous injection of testosterone propionate (5.0 mg/kg/b.w) for 28 consecutive days. Plant extract in vitro antioxidant activities were determined. After 14 days post-treatment, a 40% increase in prostate weight in the TC reflected a significant increase (p<0.05) in prostate index. The AMM and AMH groups showed significant reductions (p<0.05) in the prostate index, at approximately 50%. Prostate inhibition percentage of the FT at 45.26% and the AML, AMM and AMH at 43.4%, 42.1% and 44.4% were non-significant (p>0.05). In vitro antioxidant capacities were exhibited at 94.4% DPPH and 60% FRAP inhibition. This study therefore suggests that A. muricata is a potential candidate for the treatment of BPH.
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Ezirim, A. U., Ezekwesili-Ofili , J. O., & Igwilo, I. O. (2024). Effect of Annona muricata leaf ethanol extract on testosterone-induced benign prostatic hyperplasia in Wistar rats. The Bioscientist Journal, 12(1), 12-23. https://doi.org/10.54117/the_bioscientist.v12i1.162
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References
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Afzaal, M., Saeed, F., Asghar, A., Shah, Y. A., Ikram, A., Ateeq, H., Hussain, M., Ofoedu, C. E. and Chacha, J. S. (2022). Nutritional and therapeutic potential of soursop. Journal of Food Quality, Article ID 8828358.
Ajonuma, L. C., Ng, E. N. Y., Chang, L. N., Chow, P. H., Kung, L. S., Chang, A. N. Y., Ho, L. S., Briton-Jones, C., Lok, I. H., Haines, C.J, and Chan, H. C. (2005). Ultrastructural characterization of whole hydrosalpinx from infertile Chinese women. Cell Biology International, 29: 849–856.
Alamoudi, A. J., Alessi, S. A., Rizg, W. Y., Jali, A. M., Safhi, A. Y.; Sabei, F.Y., Alshehri, S., Hosny, K. M. and Abdel-Naim, A. B. (2022). Cordycepin attenuates testosterone-induced benign prostatic hyperplasia in rats via modulation of AMPK and AKT Activation. Pharmaceutics, 14 (8):1652.
Baskar, R., Rajeswari, V. and Kumar, T. S. (2007). In-vitro antioxidant studies in leaves of Annona species. Indian Journal of Experimental Biology, 45 (5): 480 – 485.
Cai, T., Santi, R., Tamanini, I., Galli, I. C., Perletti, G., Bjerklund-Johansen, T. E. and Nesi G. (2019). Current knowledge of the potential links between inflammation and prostate cancer. International Journal of Molecular Sciences, 20 (15): 3833.
Campolina-Silva, G. H., Werneck-Gomes, H., Maria, B. T., Barata, M. C., Torres, M. J., Contreras, H. R., Mahecha, G. A. B., Oliveira, C. A. (2020). Targeting Wistar rat as a model for studying benign, premalignant and malignant lesions of the prostate. Life Sciences, 242: 117149.
Choi, Y. J., Lee, J. I., Fan, M., Tang, Y., Yoon, E. J., Ryu, Y. B. and Kim, E. K. (2020). Metabolomic analysis of Morus cultivar root extracts and their ameliorative effect on testosterone-induced prostate enlargement in Sprague Dawley rats. International Journal of Molecular Sciences, 21 (4): 1435.
Clayden, E. C. (1967). Practical section cutting and staining, 4th edn. J and E ChurchHill Ltd, UK.
da Rocha, A. B., Lopes, R. M. and Schwartsmann, G. (2001). Natural products in anticancer therapy. Current Opinion in Pharmacology, 4 (1): 364-369.
de Sousa O.V., Vieira G. D., Pinho J. J. R., Yamamoto, C.H., and Alves, M.S. (2010). Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. International Journal of Molecular Sciences, 11 (5): 2067-2078.
Devlin, C. M., Simms, M. S. and Maitland, N. J. (2021). Benign prostatic hyperplasia–what do we know? British Journal of Urology International, 127 (4): 389-399.
Dorman, H. J., Kosar, M., Kahlos, K., Holm, Y., and Hiltunen, R. (2003). Antioxidant properties and composition of aqueous extracts from Mentha species, hybrids, varieties, and cultivars. Journal of Agricultural and Food Chemistry, 51: 4563-4569.
Ejike, C.E.C. and Ezeanyika, L.U.S. (2011). Management of experimental benign prostatic hyperplasia in rats using a feedbased therapy containing Telfairia occidentalis seeds. African Journal of Traditional, Complementary, and Alternative Medicine. 8 (4): 398–404.
Ekeyi, Y., Uchendu, N. O., Anaduaka, E. G. and Ezeanyika, L.U.S (2021). Ethanol extract of Cassia sieberiana leaves ameliorates deviances associated with benign prostatic hyperplasia in rats. All Life, 14 (1): 473-483.
Ezirim, A. U., Okochi, V. I., James, A. B., Adebeshi, O. A., Ogunnowo S. and Odeghe, O. B. (2013). Induction of apoptosis in myelogenous leukemic K562 cells by ethanolic leaf extract of Annona muricata. Global Journal of Research on Medicinal Plants & Indigenous Medicine, 2 (3): 142-151.
Fibbi, B., Penna, G., Morelli, A., Adorini, L., and Maggi, M. (2010). Chronic inflammation in the pathogenesis of benign prostatic hyperplasia. International Journal of Andrology, 33 (3): 475-488.
Gavamukulya, Y., Abou-Elella, F., Wamunyokoli, F., and El-Shemy, H. A. (2015). GC-MS analysis of bioactive phytochemicals present in ethanolic extracts of leaves of Annona muricata: A further evidence for its medicinal diversity. Pharmacognosy Journal, 7 (5): 300-304.
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite and 15N in biological fluids. Analytical Biochemistry, 126: 131–136.
John, D. B. and Alan, S. (1977) Theory and practice of histological techniques. Churchill Livingstone, Edinburgh.
Kapoor, A. (2012). Benign prostatic hyperplasia (BPH) management in the primary care setting. Canadian Journal of Urology, 19 (1): 10-17.
Leon-Fernandez, A. E., Sayago-Ayerdi, S. G., Velazquez-Estrada, R. M., Zepeda-Vallejo, L. G., Yahia, E. and Montalvo-Gonzalez E. (2017). In-vitro antioxidant capacity of crude extracts and acetogenin fraction of soursop fruit pulp. Pharmaceutica Analytica Acta, 8 (6): 550 – 556.
Liu, N., Yang, H. L., Wang, P., Lu, Y. C., Yang, Y. J. and Wang, L. (2016). Functional proteomic analysis reveals that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. Journal of Ethnopharmacology, 189: 210–217.
Lorke, D. (1983). A new approach to practical acute toxicity testing. Archives of Toxicology, 54: 275–87.
Madersbacher, S., Sampson, N. and Culig, Z. (2019). Pathophysiology of benign prostatic hyperplasia and benign prostatic enlargement: A Mini-Review. Gerontology, 65:458-464.
Maghsoudi, H., Hallajzadeh, J., and Rezaeipour, M. (2018). Evaluation of the effect of polyphenol of escin compared with ibuprofen and dexamethasone in synoviocyte model for osteoarthritis: an in vitro study. Clinical Rheumatology, 37 (9): 2471-2478.
Mahapokai, W., Van Sluijs, F. J., and Schalken, J. A. (2000). Models for studying benign prostatic hyperplasia. Prostate Cancer and Prostatic Diseases, 3 (1): 28-33.
Mallick, C. P. and Singh, M. B. (1980). Plant enzymology and plant histoenzymology. Kalaya Publishing, New Delhi.
Mbaka, G., Anunobi, C., Ogunsina, S. and Osiagwu, D. (2017). Histomorphological changes in induced benign prostatic hyperplasia with exogenous testosterone and estradiol in adult male rats treated with aqueous ethanol extract of Secamone afzelii. Egyptian Journal of Basic and Applied Sciences, 4: 15–21.
Mensor, L. L., Menezes, F. S., Leitão, G. G., Reis, A. S., Santos, T. C. D., Coube, C. S., and Leitão, S. G. (2001). Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytotherapy Research, 15 (2): 127-130.
Nwaehujor, I., Olatunji, G., Oluwatoyin, F. and Samuel, A. (2020). Antioxidant and anti-inflammatory potential, and chemical composition of fractions of ethanol extract of Annona muricata leaf. Ruhuna Journal of Science. 11, 131.
Orak, H. H., Bahrisefit, I. S. and Sabudak, T. (2019). Antioxidant activity of the extracts of soursop (Annona muricata L.) leaves, fruits pulps, peels and seeds. Polish Journal of Food and Nutrition Sciences, 69 (4): 359 – 366.
Phua, T. J. (2021). The etiology and pathophysiology genesis of benign prostatic hyperplasia and prostate cancer: A New Perspective. Medicines, 8 (6):30.
Pulido, R., Bravo, L., and Saura-Calixto, F. (2000). Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. Journal of Agricultural and Food Chemistry, 48: 3396–3402.
Raafat, M., Kamel, A. A., Shehata, A.H., Ahmed, A. S. F., Bayoumi, A. M. A., Moussa, R. A., Abourehab, M.A.S. and El-Daly, M. (2022). Aescin protects against experimental benign prostatic hyperplasia and preserves prostate histomorphology in rats via suppression of inflammatory cytokines and COX-2. Pharmaceuticals, 15, 130.
Shabani, E., Kalantari, H., Kalantar, M., Goudarzi, M., Mansouri, E. and Kalantar, H. (2021). Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats. BMC Complementary Medicine and Therapies, 21(1): 1-10.
Singh, R. (2015). Medicinal plants: A review. Journal of Plant Sciences, 3 (1):50–55.
Sun, S., Liu, J., Zhou, N., Zhu, W., Dou, Q. P., and Zhou, K. (2016). Isolation of three new annonaceous acetogenins from graviola fruit (Annona muricata) and their anti-proliferation on human prostate cancer cell PC-3. Bioorganic & Medicinal Chemistry Letters, 26: 4382–4385.
Untergasser G., Madersbacher S., and Berger P. (2005). Benign prostatic hyperplasia: age-related tissue-remodeling, Experimental Gerontology, 40 (3): 121-128.
Wahab, S. M., Jantan, I., Haque, M. A. and Arshad, L. (2018). Exploring the Leaves of Annona muricata L. as a source of potential anti-inflammatory and anticancer agents. Frontiers in Pharmacology, 9: 661.
Wang, C. T., Wang, Y. Y., Liu, W. S., Cheng, C. M., Chiu, K. H., Liu, L. L., Liu, X. Z., Wen, Z. H., Chen, Y. H., and Chen, T. M. (2018). Rhodobacter sphaeroides extract Lycogen™ attenuates testosterone-induced benign prostate hyperplasia in rats. International Journal of Molecular Sciences, 19 (4): 1137.
Yang, C., Gundala, S. R., Mukkavilli, R., Vangala, S., Reid, M. D., and Aneja, R. (2015). Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis, 36: 656–665.
Afzaal, M., Saeed, F., Asghar, A., Shah, Y. A., Ikram, A., Ateeq, H., Hussain, M., Ofoedu, C. E. and Chacha, J. S. (2022). Nutritional and therapeutic potential of soursop. Journal of Food Quality, Article ID 8828358.
Ajonuma, L. C., Ng, E. N. Y., Chang, L. N., Chow, P. H., Kung, L. S., Chang, A. N. Y., Ho, L. S., Briton-Jones, C., Lok, I. H., Haines, C.J, and Chan, H. C. (2005). Ultrastructural characterization of whole hydrosalpinx from infertile Chinese women. Cell Biology International, 29: 849–856.
Alamoudi, A. J., Alessi, S. A., Rizg, W. Y., Jali, A. M., Safhi, A. Y.; Sabei, F.Y., Alshehri, S., Hosny, K. M. and Abdel-Naim, A. B. (2022). Cordycepin attenuates testosterone-induced benign prostatic hyperplasia in rats via modulation of AMPK and AKT Activation. Pharmaceutics, 14 (8):1652.
Baskar, R., Rajeswari, V. and Kumar, T. S. (2007). In-vitro antioxidant studies in leaves of Annona species. Indian Journal of Experimental Biology, 45 (5): 480 – 485.
Cai, T., Santi, R., Tamanini, I., Galli, I. C., Perletti, G., Bjerklund-Johansen, T. E. and Nesi G. (2019). Current knowledge of the potential links between inflammation and prostate cancer. International Journal of Molecular Sciences, 20 (15): 3833.
Campolina-Silva, G. H., Werneck-Gomes, H., Maria, B. T., Barata, M. C., Torres, M. J., Contreras, H. R., Mahecha, G. A. B., Oliveira, C. A. (2020). Targeting Wistar rat as a model for studying benign, premalignant and malignant lesions of the prostate. Life Sciences, 242: 117149.
Choi, Y. J., Lee, J. I., Fan, M., Tang, Y., Yoon, E. J., Ryu, Y. B. and Kim, E. K. (2020). Metabolomic analysis of Morus cultivar root extracts and their ameliorative effect on testosterone-induced prostate enlargement in Sprague Dawley rats. International Journal of Molecular Sciences, 21 (4): 1435.
Clayden, E. C. (1967). Practical section cutting and staining, 4th edn. J and E ChurchHill Ltd, UK.
da Rocha, A. B., Lopes, R. M. and Schwartsmann, G. (2001). Natural products in anticancer therapy. Current Opinion in Pharmacology, 4 (1): 364-369.
de Sousa O.V., Vieira G. D., Pinho J. J. R., Yamamoto, C.H., and Alves, M.S. (2010). Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. International Journal of Molecular Sciences, 11 (5): 2067-2078.
Devlin, C. M., Simms, M. S. and Maitland, N. J. (2021). Benign prostatic hyperplasia–what do we know? British Journal of Urology International, 127 (4): 389-399.
Dorman, H. J., Kosar, M., Kahlos, K., Holm, Y., and Hiltunen, R. (2003). Antioxidant properties and composition of aqueous extracts from Mentha species, hybrids, varieties, and cultivars. Journal of Agricultural and Food Chemistry, 51: 4563-4569.
Ejike, C.E.C. and Ezeanyika, L.U.S. (2011). Management of experimental benign prostatic hyperplasia in rats using a feedbased therapy containing Telfairia occidentalis seeds. African Journal of Traditional, Complementary, and Alternative Medicine. 8 (4): 398–404.
Ekeyi, Y., Uchendu, N. O., Anaduaka, E. G. and Ezeanyika, L.U.S (2021). Ethanol extract of Cassia sieberiana leaves ameliorates deviances associated with benign prostatic hyperplasia in rats. All Life, 14 (1): 473-483.
Ezirim, A. U., Okochi, V. I., James, A. B., Adebeshi, O. A., Ogunnowo S. and Odeghe, O. B. (2013). Induction of apoptosis in myelogenous leukemic K562 cells by ethanolic leaf extract of Annona muricata. Global Journal of Research on Medicinal Plants & Indigenous Medicine, 2 (3): 142-151.
Fibbi, B., Penna, G., Morelli, A., Adorini, L., and Maggi, M. (2010). Chronic inflammation in the pathogenesis of benign prostatic hyperplasia. International Journal of Andrology, 33 (3): 475-488.
Gavamukulya, Y., Abou-Elella, F., Wamunyokoli, F., and El-Shemy, H. A. (2015). GC-MS analysis of bioactive phytochemicals present in ethanolic extracts of leaves of Annona muricata: A further evidence for its medicinal diversity. Pharmacognosy Journal, 7 (5): 300-304.
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite and 15N in biological fluids. Analytical Biochemistry, 126: 131–136.
John, D. B. and Alan, S. (1977) Theory and practice of histological techniques. Churchill Livingstone, Edinburgh.
Kapoor, A. (2012). Benign prostatic hyperplasia (BPH) management in the primary care setting. Canadian Journal of Urology, 19 (1): 10-17.
Leon-Fernandez, A. E., Sayago-Ayerdi, S. G., Velazquez-Estrada, R. M., Zepeda-Vallejo, L. G., Yahia, E. and Montalvo-Gonzalez E. (2017). In-vitro antioxidant capacity of crude extracts and acetogenin fraction of soursop fruit pulp. Pharmaceutica Analytica Acta, 8 (6): 550 – 556.
Liu, N., Yang, H. L., Wang, P., Lu, Y. C., Yang, Y. J. and Wang, L. (2016). Functional proteomic analysis reveals that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. Journal of Ethnopharmacology, 189: 210–217.
Lorke, D. (1983). A new approach to practical acute toxicity testing. Archives of Toxicology, 54: 275–87.
Madersbacher, S., Sampson, N. and Culig, Z. (2019). Pathophysiology of benign prostatic hyperplasia and benign prostatic enlargement: A Mini-Review. Gerontology, 65:458-464.
Maghsoudi, H., Hallajzadeh, J., and Rezaeipour, M. (2018). Evaluation of the effect of polyphenol of escin compared with ibuprofen and dexamethasone in synoviocyte model for osteoarthritis: an in vitro study. Clinical Rheumatology, 37 (9): 2471-2478.
Mahapokai, W., Van Sluijs, F. J., and Schalken, J. A. (2000). Models for studying benign prostatic hyperplasia. Prostate Cancer and Prostatic Diseases, 3 (1): 28-33.
Mallick, C. P. and Singh, M. B. (1980). Plant enzymology and plant histoenzymology. Kalaya Publishing, New Delhi.
Mbaka, G., Anunobi, C., Ogunsina, S. and Osiagwu, D. (2017). Histomorphological changes in induced benign prostatic hyperplasia with exogenous testosterone and estradiol in adult male rats treated with aqueous ethanol extract of Secamone afzelii. Egyptian Journal of Basic and Applied Sciences, 4: 15–21.
Mensor, L. L., Menezes, F. S., Leitão, G. G., Reis, A. S., Santos, T. C. D., Coube, C. S., and Leitão, S. G. (2001). Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytotherapy Research, 15 (2): 127-130.
Nwaehujor, I., Olatunji, G., Oluwatoyin, F. and Samuel, A. (2020). Antioxidant and anti-inflammatory potential, and chemical composition of fractions of ethanol extract of Annona muricata leaf. Ruhuna Journal of Science. 11, 131.
Orak, H. H., Bahrisefit, I. S. and Sabudak, T. (2019). Antioxidant activity of the extracts of soursop (Annona muricata L.) leaves, fruits pulps, peels and seeds. Polish Journal of Food and Nutrition Sciences, 69 (4): 359 – 366.
Phua, T. J. (2021). The etiology and pathophysiology genesis of benign prostatic hyperplasia and prostate cancer: A New Perspective. Medicines, 8 (6):30.
Pulido, R., Bravo, L., and Saura-Calixto, F. (2000). Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. Journal of Agricultural and Food Chemistry, 48: 3396–3402.
Raafat, M., Kamel, A. A., Shehata, A.H., Ahmed, A. S. F., Bayoumi, A. M. A., Moussa, R. A., Abourehab, M.A.S. and El-Daly, M. (2022). Aescin protects against experimental benign prostatic hyperplasia and preserves prostate histomorphology in rats via suppression of inflammatory cytokines and COX-2. Pharmaceuticals, 15, 130.
Shabani, E., Kalantari, H., Kalantar, M., Goudarzi, M., Mansouri, E. and Kalantar, H. (2021). Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats. BMC Complementary Medicine and Therapies, 21(1): 1-10.
Singh, R. (2015). Medicinal plants: A review. Journal of Plant Sciences, 3 (1):50–55.
Sun, S., Liu, J., Zhou, N., Zhu, W., Dou, Q. P., and Zhou, K. (2016). Isolation of three new annonaceous acetogenins from graviola fruit (Annona muricata) and their anti-proliferation on human prostate cancer cell PC-3. Bioorganic & Medicinal Chemistry Letters, 26: 4382–4385.
Untergasser G., Madersbacher S., and Berger P. (2005). Benign prostatic hyperplasia: age-related tissue-remodeling, Experimental Gerontology, 40 (3): 121-128.
Wahab, S. M., Jantan, I., Haque, M. A. and Arshad, L. (2018). Exploring the Leaves of Annona muricata L. as a source of potential anti-inflammatory and anticancer agents. Frontiers in Pharmacology, 9: 661.
Wang, C. T., Wang, Y. Y., Liu, W. S., Cheng, C. M., Chiu, K. H., Liu, L. L., Liu, X. Z., Wen, Z. H., Chen, Y. H., and Chen, T. M. (2018). Rhodobacter sphaeroides extract Lycogen™ attenuates testosterone-induced benign prostate hyperplasia in rats. International Journal of Molecular Sciences, 19 (4): 1137.
Yang, C., Gundala, S. R., Mukkavilli, R., Vangala, S., Reid, M. D., and Aneja, R. (2015). Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis, 36: 656–665.