Effect of Methanol Stem Bark Extract of Annona senegalensis on Haematological Profile in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats
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394-418
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Sep 9, 2025
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10.58578/ajcmpr.v2i3.7364
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Authors:
Isaac John Umaru1, Panah Philemon2, Ingwu Joseph Akem3, Mosugu Ovayoza Omolara4, Ogar Fonne Okang5, Akafa Andes Tansaba6, Shadrach Philip7, Otashu Kenneth Frank8 
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Abstract
Liver cancer, particularly hepatocellular carcinoma (HCC), is a leading cause of mortality worldwide and is frequently associated with hematological complications such as anemia and impaired blood clotting. This study evaluated the hematoprotective effects of methanol stem-bark extract of Annona senegalensis in rats with diethylnitrosamine (DEN)-induced HCC. Fifty-four male rats were allocated into six groups: a normal control group, a DEN-induced group without treatment, a positive control group treated with silymarin, and three treatment groups administered varying doses of A. senegalensis extract. Hematological parameters assessed included red blood cells (RBC), hemoglobin (HGB), white blood cells (WBC), hematocrit (HCT), and platelets (PLT). DEN induction significantly reduced RBC, HGB, and PLT levels, indicating anemia and coagulation impairment. Treatment with A. senegalensis, particularly at 400 mg/kg, markedly improved these hematological indices, suggesting a restorative effect on blood parameters. The protective role of the extract may be attributed to its bioactive constituents, such as flavonoids, alkaloids, and tannins, known for their antioxidant and anti-inflammatory activities. These findings suggest that A. senegalensis possesses promising hematoprotective potential in the management of blood-related complications associated with liver cancer. Further research, including mechanistic studies and clinical trials, is warranted to validate its safety and therapeutic efficacy in humans.
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Methanol; Stem Bark Extract; Annona senegalensis; Hematological Parameters; Diethylnitrosamine; Hepatocellular Carcinoma; Wistar Rats
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Umaru, I. J., Philemon, P., Akem, I. J., Omolara, M. O., Okang, O. F., Tansaba, A. A., Philip, S., & Frank, O. K. (2025). Effect of Methanol Stem Bark Extract of Annona senegalensis on Haematological Profile in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats. African Journal of Clinical Medicine and Pharmacy Research, 2(3), 394-418. https://doi.org/10.58578/ajcmpr.v2i3.7364
References
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Okwu, D. E. (2004). Phytochemicals and vitamin content of indigenous spices of South Eastern Nigeria. Journal of Sustainable Agriculture and Environment, 6(1), 30–37.
Okwu, D. E., and Emenike, I. N. (2006). Evaluation of the phytonutrients and vitamin contents of citrus fruits. Journal of Medicinal and Aromatic Plant Sciences, 28(3), 44–49.
Okwu, D. E., and Morah, F. N. (2007). Phytochemical analysis and antimicrobial activity of Annona senegalensis extracts. African Journal of Biotechnology, 6(2), 124–129.
Okwu, D. E., and Omodamiro, O. D. (2005). Comparative analysis of the bioactive compounds in traditional medicinal plants. Nigerian Journal of Natural Products and Medicine, 9(3), 105–110.
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Yi, L., Ma, S., and Ren, D. (2017). Phytochemistry and bioactivity of Citrus flavonoids: a focus on antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Phytochemistry Reviews, 16, 479-511.
Acharya, S. K. (2014). Epidemiology of hepatocellular carcinoma in India. Journal of clinical and experimental hepatology, 4, S27-S33.
Adebayo, A. H., Aliyu, R., Gatsing, D., and Garba, I. H. (2011). The effects of ethanolic extract of Annona senegalensis on lipid profile and hematological parameters in albino rats. African Journal of Traditional, Complementary and Alternative Medicines, 8(1), 34–39.
Akaneme, F. I. (2008). Genetic diversity of Annona senegalensis using RAPD markers. International Journal of Botany, 4(3), 336–340.
Alrumaihi, F., Almatroodi, S. A., Alharbi, H. O. A., Alwanian, W. M., Alharbi, F. A., Almatroudi, A., and Rahmani, A. H. (2024). Pharmacological potential of kaempferol, a flavonoid in the management of pathogenesis via modulation of inflammation and other biological activities. Molecules, 29(9), 2007-2056.
Amadi, E. N., Agomuo, E. N., and Ibegbulem, C. O. (2000). Nutritional composition of Annona senegalensis leaves and seeds. West African Journal of Pharmacology and Drug Research, 16(2), 89–95.
Amuzat, A. O., Sulaiman, R. S., Yusuf, A. A., Mohammed, H., Ndatsu, Y., Adamu, M., and Idris, F. Z. (2020). METHANOL EXTRACT OF Vitex doniana (black plum) stem bark modulates hematological parameters, lipid profile and renal indices in castor-oil induced diarrhoeal wistar rat. Lapai Journal of Science and Technology, 6(1), 146-166.
Asare, G. A., Addo, P., Mensah, P., and Otu-Nyarko, L. (2015). Phytochemical and pharmacological activities of Annona senegalensis: A review. Pharmacognosy Research, 7(4), 312–319.
Attanayake, P., Rupasinghe, D., Gamage, A., Madhujith, T., and Merah, O. (2024). Chemopreventive Potential of Oils Extracted from Seeds of Three Annona Species. Seeds, 3(1), 105-122.
Burits, M., and Bucar, F. (2002). Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research, 16(5), 323–328.
Chen, H., and Luo, D. (2023). Application of haematology parameters for health management in fish farms. Reviews in Aquaculture, 15(2), 704-737.
Choumessi, E. T., Kuete, V., Danel, M., and Tchaleu, B. (2012). Anticancer properties of Annona senegalensis extracts. Journal of Ethnopharmacology, 140(2), 331–336.
Dede, E. B., Uwakwe, A. A., and Ekundayo, O. (2002). Antimicrobial and anti-inflammatory properties of Annona senegalensis. African Journal of Biochemistry Research, 5(1), 19–27.
Diallo, D., Dramé, A., Niang, L., Badock, E. A., Diallo, I., Sow, S., and Ayessou, N. C. (2024). Phytochemical Screening and Antioxidant Activity of Annona Senegalensis Extracts (Leaves and Stem Bark) Collected from Three Regions of Senegal. Advances in Biochemistry, 12(3), 105-111.
Guo, H., Ahn, S., and Zhang, L. (2021). Benzene-associated immunosuppression and chronic inflammation in humans: a systematic review. Occupational and environmental medicine, 78(5), 377-384.
Idowu, O. A., Soniran, O. T., Ajana, O., and Aworinde, D. O. (2003). Ethnobotanical survey of anti-malarial plants used in Ogun State, Nigeria. Journal of Ethnobotany and Medicinal Plants, 12(4), 67–73.
Idowu, O. A., Soniran, O. T., Ajana, O., and Aworinde, D. O. (2006). Phytochemical screening and antimicrobial activity of Annona senegalensis leaf extracts. African Journal of Biochemistry and Molecular Biology, 8(2), 54–60.
Johnson, S. B., Park, H. S., Gross, C. P., and James, B. Y. (2018). Complementary medicine, refusal of conventional cancer therapy, and survival among patients with curable cancers. JAMA oncology, 4(10), 1375-1381.
Khan, F., Khan, T. J., Kalamegam, G., Pushparaj, P. N., Chaudhary, A., Abuzenadah, A.,. and Al-Qahtani, M. (2017). Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. BMC complementary and alternative medicine, 17, 1-10
Li, Y., and Hecht, S. S. (2022). Metabolic activation and DNA interactions of carcinogenic N-nitrosamines to which humans are commonly exposed. International journal of molecular sciences, 23(9), 4559.
Lurje, I., Czigany, Z., Bednarsch, J., Roderburg, C., Isfort, P., Neumann, U. P., and Lurje, G. (2019). Treatment strategies for hepatocellular carcinoma—a multidisciplinary approach. International journal of molecular sciences, 20(6), 1465.
Mahmoud, A. D., Al-Rawi, S. S., and Hama, H. A. (2025). Traditional uses, bioactive compounds and pharmacological uses of Vitex doniana Sweet: A Review. Ethnobotany Research and Applications, 30, 1-130.
Malabadi, R. B., Sadiya, M. R., Kolkar, K. P., Mammadova, S. S., Chalannavar, R. K., Baijnath, H.,. and Munhoz, A. N. R. (2024). Triple Negative Breast Cancer (TNBC): Signalling pathways-Role of plant-based inhibitors. Open Access Research Journal of Biology and Pharmacy, 10(2), 028-071.
Mansour, A., Eisa, M., Abdelghany, T., and Salama, S. (2022). Silymarin ameliorates diethylnitrosamine-induced liver fibrosis in Wistar rats. Al-Azhar Journal of Pharmaceutical Sciences, 66(2), 246-266.
Mustapha, A., Ismail, A., Abdullahi, S. U., Hassan, O. N., Ugwunnaji, P. I., and Berinyuy, E. B. (2022). Cancer chemotherapy: a review update of the mechanisms of actions, prospects and associated problems. J Biomed, 1(01), 001-16.
Okoye, T. C., Akah, P. A., Ezike, A. C., Okoye, M. O., Onyeto, C. A., Ndukwu, F., and Ikele, L. (2012). Evaluation of the acute and sub acute toxicity of Annona senegalensis root bark extracts. Asian Pacific Journal of Tropical Medicine, 5(4), 277-282.
Okwu, D. E. (2004). Phytochemicals and vitamin content of indigenous spices of South Eastern Nigeria. Journal of Sustainable Agriculture and Environment, 6(1), 30–37.
Okwu, D. E., and Emenike, I. N. (2006). Evaluation of the phytonutrients and vitamin contents of citrus fruits. Journal of Medicinal and Aromatic Plant Sciences, 28(3), 44–49.
Okwu, D. E., and Morah, F. N. (2007). Phytochemical analysis and antimicrobial activity of Annona senegalensis extracts. African Journal of Biotechnology, 6(2), 124–129.
Okwu, D. E., and Omodamiro, O. D. (2005). Comparative analysis of the bioactive compounds in traditional medicinal plants. Nigerian Journal of Natural Products and Medicine, 9(3), 105–110.
Olorunnisola, O. S., Afolayan, A. J., and Eloff, J. N. (2008). Antioxidant properties and phytochemical screening of Annona senegalensis. Journal of Pharmacognosy and Phytotherapy, 2(6), 98–105.
Onwurah, F. B., and Eze, C. N. (2000). Biochemical and pharmacological properties of Annona senegalensis. West African Journal of Pharmacology and Drug Research, 17(1), 74–82.
Ordinioha, B., and Brisibe, S. (2013). Health benefits and pharmacological activities of Annona senegalensis. Journal of Public Health and Epidemiology, 5(9), 212–220.
Patrick-Iwuanyanwu, K. C., Wegwu, M. O., and Ayalogu, E. O. (2011). Hepatoprotective effects of Annona senegalensis extract in rats. African Journal of Biochemistry Research, 7(3), 49–56.
Ruhnke, M., Cornely, O. A., Schmidt‐Hieber, M., Alakel, N., Boell, B., Buchheidt, D.,. and Schwartz, S. (2020). Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Mycoses, 63(7), 653-682.
Sankar, V., and Villa, A. (2021). Hematologic diseases. Burket 's Oral Medicine, 627-664.
Schulien, I., and Hasselblatt, P. (2021). Diethylnitrosamine-induced liver tumorigenesis in mice. Methods in Cell Biology, 163, 137-152.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30
Tukur, A., Musa, N. M., Bello, H. A., and Sani, N. A. (2020). Determination of the phytochemical constituents and antifungal properties of Annona senegalensis leaves (African custard apple). ChemSearch Journal, 11(1), 16-24.
Udodeme, O. H., I Nwafor, F., P Omeke, C., and O Ezugwu, C. (2019). Antioxidant and hepatoprotective properties from the extract and fractions of Annona senegalensis Pers (Annonaceae) stem bark grown in Nigeria. European Journal of Medicinal Plants, 28(4), 1-13.
Ukana, D. A., Uwakwe, A. A., and Okokon, J. E. (2012). Phytochemical and nutritional analysis of Annona senegalensis. Journal of Medicinal Plants Studies, 10(1), 123–130.
Vicidomini, C., Palumbo, R., Moccia, M., and Roviello, G. N. (2024). Oxidative Processes and Xenobiotic Metabolism in Plants: Mechanisms of Defense and Potential Therapeutic Implications. Journal of Xenobiotics, 14(4), 1541-1569.
Wang, S. Y., Chen, P. F., and Wang, C. Y. (2011). Antioxidant properties and phytochemical composition of Annona senegalensis. Journal of Natural Products, 74(2), 202–208.
Xing, W., Chen, D. T., Pan, J. H., Chen, Y. H., Yan, Y., Li, Q.,. and Zeng, W. A. (2017). Lidocaine induces apoptosis and suppresses tumor growth in human hepatocellular carcinoma cells in vitro and in a xenograft model in vivo. Anesthesiology, 126(5), 868-881.
Yi, L., Ma, S., and Ren, D. (2017). Phytochemistry and bioactivity of Citrus flavonoids: a focus on antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Phytochemistry Reviews, 16, 479-511.