Effect of Methanol Stem Bark Extract of Annona senegalensis as an Antibacterial Agent and on Liver Enzyme Markers in Diethyl Nitrosamine-Induced Hepatocellular Carcinoma in Rats
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523-542
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Sep 9, 2025
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10.58578/ajmsphr.v2i3.7361
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Authors:Isaac John Umaru1, Emmanuel Efongwa2, Mosugu Ovayoza Omolara3, Ogar Fonne Okang4, Ingwu Joseph Akem5, Akafa Andes Tansaba6, Shadrach Philip7, Otashu Kenneth Frank8
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Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, frequently linked to exposure to chemical carcinogens such as diethylnitrosamine (DEN). Medicinal plants have emerged as promising sources of bioactive compounds with potential anticancer and antimicrobial properties. This study evaluated the therapeutic potential of methanol stem-bark extract of Annona senegalensis against DEN-induced hepatocellular carcinoma and selected bacterial pathogens. Fifty-four male albino rats were allocated into six groups, with hepatocarcinogenesis induced by DEN, followed by a 14-day treatment with varying doses of the extract. Hepatoprotective effects were assessed using liver enzyme markers and serum protein levels, while antibacterial activity was determined via disc diffusion assays against Staphylococcus aureus and Escherichia coli. Results demonstrated that the extract significantly reduced liver enzyme levels (ALT, AST, ALP) and improved serum proteins (total protein and albumin) at higher doses (400 and 600 mg/kg), indicating hepatoprotective potential. Bilirubin levels also improved, suggesting reduced liver stress. Antibacterial evaluation revealed dose-dependent activity, with strong inhibition against S. aureus comparable to tetracycline at 200 µg/mL, and moderate efficacy against E. coli. These findings highlight the dual therapeutic potential of A. senegalensis stem-bark extract as both a hepatoprotective and antibacterial agent. Future studies are recommended to isolate and characterize the bioactive compounds responsible for these effects and to expand antibacterial evaluation to a wider spectrum of pathogens.
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Stem-Bark Extract; Annona senegalensis; Antibacterial Activity; Liver Enzyme Markers; Diethylnitrosamine; Hepatocellular Carcinoma; Wistar Rats
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Umaru, I. J., Efongwa, E., Omolara, M. O., Okang, O. F., Akem, I. J., Tansaba, A. A., Philip, S., & Frank, O. K. (2025). Effect of Methanol Stem Bark Extract of Annona senegalensis as an Antibacterial Agent and on Liver Enzyme Markers in Diethyl Nitrosamine-Induced Hepatocellular Carcinoma in Rats. African Journal of Medicine, Surgery and Public Health Research, 2(3), 523-542. https://doi.org/10.58578/ajmsphr.v2i3.7361
References
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Al Kazman, B. S., Harnett, J. E. and Hanrahan, J. R. (2022). Traditional uses, phytochemistry and pharmacological activities of annonacae. Molecules, 27(11), 3462.
Alamgir, A. N. M. (2017). Therapeutic use of medicinal plants and their extracts: volume 1. Springer International Publishing AG.
Ballester, P., Cerdá, B., Arcusa, R., Marhuenda, J., Yamedjeu, K. and Zafrilla, P. (2022). Effect of ginger on inflammatory diseases. Molecules, 27(21), 7223.
Bhardwaj, R., Pareek, S., Sagar, N. A. and Vyas, N. (2020). Bioactive compounds of Annona. Bioactive compounds in underutilized fruits and nuts, 37-62.
Bolajoko, E. B., Attah, A. F., Akinosun, O. M., Onyeaghala, A. A., Moody, J. O. and Khine, A. A. (2019). Metal contents and acute toxicity of combined Vernonia amygdalina leaves and Garcinia kola seeds-VAGK, a herbal and nutritional formulation in male wistar rats. African Journal of Biomedical Research, 22(2), 187-194.
Connor, F., Rayner, T. F., Aitken, S. J., Feig, C., Lukk, M., Santoyo-Lopez, J. and Odom, D. T. (2018). Mutational landscape of a chemically-induced mouse model of liver cancer. Journal of hepatology, 69(4), 840-850.
Djoza, R. D., Ashande, C. M. and Mpiana, P. T. (2017). A mini-review on the pharmacognosy and phytochemistry of a tropical medicinal plant: Annona senegalese Pers.(Annonaceae). Tropical plant research, 4, 168-175.
Emmanuel, A., Ebinbin, A. and Amlabu, W. (2014). Detoxification of Echis ocellatus venom-induced toxicity by Annona senegalese Pers. Journal of Complementary and Integrative Medicine, 11(2), 93-97.
Emmanuel, N. and Mamoudou, S. (2015). Some Investigations on the Traditional Pharmacopoeia about Venomous Bites and Stings from Scorpions, Snakes and Spiders; in the Hina Subdivision, Far-North, Cameroon. British Journal of Pharmaceutical Research, 5(5), 344-358.
Hou, Y., Hu, S., Li, X., He, W. and Wu, G. (2020). Amino acid metabolism in the liver: nutritional and physiological significance. Amino Acids in Nutrition and Health: Amino acids in systems function and health, 21-37.
Irfan, M., Kwak, Y. S., Han, C. K., Hyun, S. H. and Rhee, M. H. (2020). Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions. Journal of Ginseng Research, 44(4), 538-543.
Izah, S. C., Ogidi, O. I., Ogwu, M. C., Salimon, S. S., Yusuf, Z. M., Akram, M. and Iyingiala, A. A. (2024). Historical perspectives and overview of the value of herbal medicine. In Herbal Medicine Phytochemistry: Applications and Trends (pp. 3-35). Cham: Springer International Publishing.
Jada, M. S., Usman, W. A. and Olabisi, A. O. (2014). Crude flavonoids isolated from the stem bark of Annona senegalese have antimicrobial activity. Journal of Advances in Biology & Biotechnology, 2(1), 24-29.
Jaiswal, Y., Liang, Z. and Zhao, Z. (2016). Botanical drugs in Ayurveda and traditional Chinese medicine. Journal of ethnopharmacology, 194, 245-259.
Jamshidi-Kia, F., Lorigooini, Z. and Amini-Khoei, H. (2017). Medicinal plants: Past history and future perspective. Journal of herbmed pharmacology, 7(1), 1-7.
Jamshidi-Kia, F., Lorigooini, Z. and Amini-Khoei, H. (2017). Medicinal plants: Past history and future perspective. Journal of herbmed pharmacology, 7(1), 1-7.
Johnson, M., Olufunmilayo, L. A., Anthony, D. O. and Olusoji, E. O. (2015). Hepatoprotective effect of ethanolic leaf extract of Vernonia amygdalina and Azadirachta indica against acetaminophen-induced hepatotoxicity in Sprague-Dawley male albino rats. American Journal of Pharmacological Sciences, 3(3), 79-86.
Johnson, T. O., Olatunde, A. and Nwachukwu, L. (2017). Phytochemical composition of Annona senegalese leaf and its antioxidant activity during Trypanosoma brucei brucei induced oxidative stress in mice. Journal of Pharmacy & Bioresources, 14(2), 219-227.
Maan, A. A., Nazir, A., Khan, M. K. I., Ahmad, T., Zia, R., Murid, M. and Abrar, M. (2018). The therapeutic properties and applications of Aloe vera: A review. Journal of Herbal Medicine, 12, 1-10.
Malesh and Satish, 2008
Mansour, D. F., Abdallah, H. M., Ibrahim, B. M., Hegazy, R. R., Esmail, R. S. and Abdel-Salam, L. O. (2019). The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver, stomach and colon: protective effect of ginger extract. Asian Pacific journal of cancer prevention: APJCP, 20(8), 2551.
Mansour, D. F., Abdallah, H. M., Ibrahim, B. M., Hegazy, R. R., Esmail, R. S. and Abdel-Salam, L. O. (2019). The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver, stomach and colon: protective effect of ginger extract. Asian Pacific journal of cancer prevention: APJCP, 20(8), 2551.
Memon A, Pyao Y, Jung Y, Lee JI, Lee WK. A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma. Int J Mol Sci. 2020 Jul 30;21(15):5461. doi: 10.3390/ijms21155461. PMID: 32751728; PMCID: PMC7432842
Musa, D. D., Anakaa, T. M. and Bashir, K. A. (2017). Phytochemical analysis of crude extracts from Annona senegalese (L) and its anti-snake venom potential on albino rats. Fudma journal of Sciences, 1(1), 139-142.
Okhale, S. E., Akpan, E., Fatokun, O. T., Esievo, K. B. and Kunle, O. F. (2016). Annona senegalese Persoon (Annonaceae): A review of its ethnomedicinal uses, biological activities and phytocompounds. Journal of Pharmacognosy and Phytochemistry, 5(2), 211-219.
Okhale, S. E., Akpan, E., Fatokun, O. T., Esievo, K. B. and Kunle, O. F. (2016). Annona senegalese Persoon (Annonaceae): A review of its ethnomedicinal uses, biological activities and phytocompounds. Journal of Pharmacognosy and Phytochemistry, 5(2), 211-219.
Quílez, A. M., Fernández-Arche, M. A., García-Giménez, M. D. and De la Puerta, R. (2018). Potential therapeutic applications of the genus Annona: Local and traditional uses and pharmacology. Journal of ethnopharmacology, 225, 244-270.
Romeiras, M. M., Duarte, M. C., Francisco-Ortega, J., Catarino, L. and Havik, P. (2018). Recovering plant data for guinea-bissau: implications for biodiversity knowledge of West Africa. Diversity, 10(4), 109.
Sayiner, M., Golabi, P. and Younossi, Z. M. (2019). Disease burden of hepatocellular carcinoma: a global perspective. Digestive diseases and sciences, 64, 910-917.
Sofowora, A., Ogunbodede, E. and Onayade, A. (2013). The role and place of medicinal plants in the strategies for disease prevention. African journal of traditional, complementary and alternative medicines, 10(5), 210-229.
Tolba, R., Kraus, T., Liedtke, C., Schwarz, M. and Weiskirchen, R. (2015). Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Laboratory animals, 49(1), 59-69.
Umaru, I. J., Badruddin, F. A., & Umaru, H. A. (2018). Phytochemical, antifungal and antibacterial potential of Leptadenia hastata stem-bark extract. MOJ Toxicol, 4(4), 263-268.
Unsal, V. and Belge-Kurutaş, E. (2017). Experimental hepatic carcinogenesis: oxidative stress and natural antioxidants. Open Access Macedonian Journal of Medical Sciences, 5(5), 686.
Van Wyk, B. E. and Wink, M. (2018). Medicinal plants of the world. Cabi.
Xu, X., Lei, Y., Chen, L., Zhou, H., Liu, H., Jiang, J. and Wu, B. (2021). Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target. Journal of Experimental & Clinical Cancer Research, 40(1), 253.
Yang, J. D., Hainaut, P., Gores, G. J., Amadou, A., Plymoth, A. and Roberts, L. R. (2019). A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nature reviews Gastroenterology & hepatology, 16(10), 589-604Mansour et al., 2019
You, Y., Zhu, F., Li, Z., Zhang, L., Xie, Y., Chinnathambi, A. and Lu, B. (2021). Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells. Biomedicine & Pharmacotherapy, 137, 111335.
You, Y., Zhu, F., Li, Z., Zhang, L., Xie, Y., Chinnathambi, A. and Lu, B. (2021). Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells. Biomedicine & Pharmacotherapy, 137, 111335.
Zakaria, Z. A., Kamisan, F. H., Kek, T. L. and Salleh, M. Z. (2020). Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats. Pharmaceutical Biology, 58(1), 478-489.
Akbar, R., Sun, J., Bo, Y., Khattak, W. A., Khan, A. A., Jin, C. and Du, D. (2024). Understanding the Influence of Secondary Metabolites in Plant Invasion Strategies: A Comprehensive Review. Plants, 13(22), 3162.
Al Kazman, B. S., Harnett, J. E. and Hanrahan, J. R. (2022). Traditional uses, phytochemistry and pharmacological activities of annonacae. Molecules, 27(11), 3462.
Alamgir, A. N. M. (2017). Therapeutic use of medicinal plants and their extracts: volume 1. Springer International Publishing AG.
Ballester, P., Cerdá, B., Arcusa, R., Marhuenda, J., Yamedjeu, K. and Zafrilla, P. (2022). Effect of ginger on inflammatory diseases. Molecules, 27(21), 7223.
Bhardwaj, R., Pareek, S., Sagar, N. A. and Vyas, N. (2020). Bioactive compounds of Annona. Bioactive compounds in underutilized fruits and nuts, 37-62.
Bolajoko, E. B., Attah, A. F., Akinosun, O. M., Onyeaghala, A. A., Moody, J. O. and Khine, A. A. (2019). Metal contents and acute toxicity of combined Vernonia amygdalina leaves and Garcinia kola seeds-VAGK, a herbal and nutritional formulation in male wistar rats. African Journal of Biomedical Research, 22(2), 187-194.
Connor, F., Rayner, T. F., Aitken, S. J., Feig, C., Lukk, M., Santoyo-Lopez, J. and Odom, D. T. (2018). Mutational landscape of a chemically-induced mouse model of liver cancer. Journal of hepatology, 69(4), 840-850.
Djoza, R. D., Ashande, C. M. and Mpiana, P. T. (2017). A mini-review on the pharmacognosy and phytochemistry of a tropical medicinal plant: Annona senegalese Pers.(Annonaceae). Tropical plant research, 4, 168-175.
Emmanuel, A., Ebinbin, A. and Amlabu, W. (2014). Detoxification of Echis ocellatus venom-induced toxicity by Annona senegalese Pers. Journal of Complementary and Integrative Medicine, 11(2), 93-97.
Emmanuel, N. and Mamoudou, S. (2015). Some Investigations on the Traditional Pharmacopoeia about Venomous Bites and Stings from Scorpions, Snakes and Spiders; in the Hina Subdivision, Far-North, Cameroon. British Journal of Pharmaceutical Research, 5(5), 344-358.
Hou, Y., Hu, S., Li, X., He, W. and Wu, G. (2020). Amino acid metabolism in the liver: nutritional and physiological significance. Amino Acids in Nutrition and Health: Amino acids in systems function and health, 21-37.
Irfan, M., Kwak, Y. S., Han, C. K., Hyun, S. H. and Rhee, M. H. (2020). Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions. Journal of Ginseng Research, 44(4), 538-543.
Izah, S. C., Ogidi, O. I., Ogwu, M. C., Salimon, S. S., Yusuf, Z. M., Akram, M. and Iyingiala, A. A. (2024). Historical perspectives and overview of the value of herbal medicine. In Herbal Medicine Phytochemistry: Applications and Trends (pp. 3-35). Cham: Springer International Publishing.
Jada, M. S., Usman, W. A. and Olabisi, A. O. (2014). Crude flavonoids isolated from the stem bark of Annona senegalese have antimicrobial activity. Journal of Advances in Biology & Biotechnology, 2(1), 24-29.
Jaiswal, Y., Liang, Z. and Zhao, Z. (2016). Botanical drugs in Ayurveda and traditional Chinese medicine. Journal of ethnopharmacology, 194, 245-259.
Jamshidi-Kia, F., Lorigooini, Z. and Amini-Khoei, H. (2017). Medicinal plants: Past history and future perspective. Journal of herbmed pharmacology, 7(1), 1-7.
Jamshidi-Kia, F., Lorigooini, Z. and Amini-Khoei, H. (2017). Medicinal plants: Past history and future perspective. Journal of herbmed pharmacology, 7(1), 1-7.
Johnson, M., Olufunmilayo, L. A., Anthony, D. O. and Olusoji, E. O. (2015). Hepatoprotective effect of ethanolic leaf extract of Vernonia amygdalina and Azadirachta indica against acetaminophen-induced hepatotoxicity in Sprague-Dawley male albino rats. American Journal of Pharmacological Sciences, 3(3), 79-86.
Johnson, T. O., Olatunde, A. and Nwachukwu, L. (2017). Phytochemical composition of Annona senegalese leaf and its antioxidant activity during Trypanosoma brucei brucei induced oxidative stress in mice. Journal of Pharmacy & Bioresources, 14(2), 219-227.
Maan, A. A., Nazir, A., Khan, M. K. I., Ahmad, T., Zia, R., Murid, M. and Abrar, M. (2018). The therapeutic properties and applications of Aloe vera: A review. Journal of Herbal Medicine, 12, 1-10.
Malesh and Satish, 2008
Mansour, D. F., Abdallah, H. M., Ibrahim, B. M., Hegazy, R. R., Esmail, R. S. and Abdel-Salam, L. O. (2019). The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver, stomach and colon: protective effect of ginger extract. Asian Pacific journal of cancer prevention: APJCP, 20(8), 2551.
Mansour, D. F., Abdallah, H. M., Ibrahim, B. M., Hegazy, R. R., Esmail, R. S. and Abdel-Salam, L. O. (2019). The carcinogenic agent diethylnitrosamine induces early oxidative stress, inflammation and proliferation in rat liver, stomach and colon: protective effect of ginger extract. Asian Pacific journal of cancer prevention: APJCP, 20(8), 2551.
Memon A, Pyao Y, Jung Y, Lee JI, Lee WK. A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma. Int J Mol Sci. 2020 Jul 30;21(15):5461. doi: 10.3390/ijms21155461. PMID: 32751728; PMCID: PMC7432842
Musa, D. D., Anakaa, T. M. and Bashir, K. A. (2017). Phytochemical analysis of crude extracts from Annona senegalese (L) and its anti-snake venom potential on albino rats. Fudma journal of Sciences, 1(1), 139-142.
Okhale, S. E., Akpan, E., Fatokun, O. T., Esievo, K. B. and Kunle, O. F. (2016). Annona senegalese Persoon (Annonaceae): A review of its ethnomedicinal uses, biological activities and phytocompounds. Journal of Pharmacognosy and Phytochemistry, 5(2), 211-219.
Okhale, S. E., Akpan, E., Fatokun, O. T., Esievo, K. B. and Kunle, O. F. (2016). Annona senegalese Persoon (Annonaceae): A review of its ethnomedicinal uses, biological activities and phytocompounds. Journal of Pharmacognosy and Phytochemistry, 5(2), 211-219.
Quílez, A. M., Fernández-Arche, M. A., García-Giménez, M. D. and De la Puerta, R. (2018). Potential therapeutic applications of the genus Annona: Local and traditional uses and pharmacology. Journal of ethnopharmacology, 225, 244-270.
Romeiras, M. M., Duarte, M. C., Francisco-Ortega, J., Catarino, L. and Havik, P. (2018). Recovering plant data for guinea-bissau: implications for biodiversity knowledge of West Africa. Diversity, 10(4), 109.
Sayiner, M., Golabi, P. and Younossi, Z. M. (2019). Disease burden of hepatocellular carcinoma: a global perspective. Digestive diseases and sciences, 64, 910-917.
Sofowora, A., Ogunbodede, E. and Onayade, A. (2013). The role and place of medicinal plants in the strategies for disease prevention. African journal of traditional, complementary and alternative medicines, 10(5), 210-229.
Tolba, R., Kraus, T., Liedtke, C., Schwarz, M. and Weiskirchen, R. (2015). Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Laboratory animals, 49(1), 59-69.
Umaru, I. J., Badruddin, F. A., & Umaru, H. A. (2018). Phytochemical, antifungal and antibacterial potential of Leptadenia hastata stem-bark extract. MOJ Toxicol, 4(4), 263-268.
Unsal, V. and Belge-Kurutaş, E. (2017). Experimental hepatic carcinogenesis: oxidative stress and natural antioxidants. Open Access Macedonian Journal of Medical Sciences, 5(5), 686.
Van Wyk, B. E. and Wink, M. (2018). Medicinal plants of the world. Cabi.
Xu, X., Lei, Y., Chen, L., Zhou, H., Liu, H., Jiang, J. and Wu, B. (2021). Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target. Journal of Experimental & Clinical Cancer Research, 40(1), 253.
Yang, J. D., Hainaut, P., Gores, G. J., Amadou, A., Plymoth, A. and Roberts, L. R. (2019). A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nature reviews Gastroenterology & hepatology, 16(10), 589-604Mansour et al., 2019
You, Y., Zhu, F., Li, Z., Zhang, L., Xie, Y., Chinnathambi, A. and Lu, B. (2021). Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells. Biomedicine & Pharmacotherapy, 137, 111335.
You, Y., Zhu, F., Li, Z., Zhang, L., Xie, Y., Chinnathambi, A. and Lu, B. (2021). Phyllanthin prevents diethylnitrosamine (DEN) induced liver carcinogenesis in rats and induces apoptotic cell death in HepG2 cells. Biomedicine & Pharmacotherapy, 137, 111335.
Zakaria, Z. A., Kamisan, F. H., Kek, T. L. and Salleh, M. Z. (2020). Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats. Pharmaceutical Biology, 58(1), 478-489.