Toxicity study and ameliorative effects of the aqueous leaf extract of Lecanoidiscus cupanioides Planch (ex. Benth) on the stress-induced ulcer

Ebere Ifejirika Ezeonyi; Earnest Oghenesuvwe Erhirhie; Felix Ahamefule Onyegbule

doi:10.62313/ijpbp.2024.159

Authors

Ebere Ifejirika Ezeonyi Chukwuemeka Odumegwu Ojukwu University, Faculty of PharmaceuticalSciences, Department of Pharmacognosy and Traditional Medicinal, Igbariam, Anambra State, Nigeria https://orcid.org/0000-0002-1201-9011
Earnest Oghenesuvwe Erhirhie Chukwuemeka Odumegwu Ojukwu University, Faculty of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Igbariam, Anambra State, Nigeria https://orcid.org/0000-0001-5230-9817
Felix Ahamefule Onyegbule Nnamdi Azikiwe University, Faculty of Pharmaceutical Sciences, Department of Pharmaceutical and MedicinalChemistry, Agulu, Anambra State, Nigeria https://orcid.org/0000-0003-2675-708X

DOI:

https://doi.org/10.62313/ijpbp.2024.159

Keywords:

Lecaniodiscus cupanioides, Toxicity studies, Stress induced ulcer, Water immersion

Abstract

Lecaniodiscus cupanioides Planch (ex. Benth) is effective in treating burns, fevers, and inflammatory conditions. This study investigates the toxicity effects of the aqueous leaf extract (ALE) of L. cupanioides and its effect on stress-induced ulcers in animal models. The plant was collected and a 1:30 (g/ml) plant powder/solvent ratio was extracted using an ultrasonic bath at 50 °C for 45 min. Up-and-down procedure was used for acute toxicity. During subacute toxicity testing, a total of 20 mice were divided into four groups of five animals each. While group 1 served as control, groups 2, 3, and 4 received 250, 500, and 1000 mg/kg of the extract daily for 21 days. On day 22^nd, animals were sacrificed and samples were collected for hematology, biochemical, and histological analyses. In the stress-induced ulcer activity, male albino mice were randomly separated into 5 groups of 5 animals, treated with the test drug, and then dissected after being stressed using the water immersion model. LD₅₀ was > 5000 mg/kg, and in biochemical examination, there was a significant decrease in the ALP level at medium and high doses (p value < 0.05) and non-significant alterations in the values of urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight and hematology parameters (p > 0.05). The histology results showed no evidence of liver and kidney toxicity. In conclusion, aqueous leaf extract of L. cupanioides was safe following a single dose (at 5000 mg/kg) and following repeated doses for 21 days (at 250, 500, and 1000 mg/kg). This study demonstrated that the extract had a significant effect on stress-induced ulcers at various dose levels when compared to the control (native, negative control, and omeprazole). The animals treated with 200mg/kg and 400mg/kg of the extract showed a significant increase in ulcer score, ulcer index, ulcer severity, and total acidity (p < 0.05). The ulcer protection ability of the aqueous plant extract was dose-dependent.

References

Abebaw, M., Mishra, B., & Gelayee, D. A. (2017). Evaluation of anti-ulcer activity of the leaf extract of Osyris quadripartita Decne.(Santalaceae) in rats. Journal of Experimental Pharmacology, 9, 1-11. https://doi.org/10.2147/JEP.S125383 DOI: https://doi.org/10.2147/JEP.S125383

Adami, T. B., Bjerk, T. R., dos Reis Souza, M. R., Cardoso, C. A., Krause, L. C., & Carama, E. B. (2020). Ultrasonic assisted extraction of bioactive compounds from different parts of Hancornia speciosa Gomes. Journal of Medicinal Plants Research, 14(7), 300-308. https://doi.org/10.5897/JMPR2020.6944 DOI: https://doi.org/10.5897/JMPR2020.6944

Alara, O. R., Abdurahman, N. H., & Ukaegbu, C. I. (2021). Extraction of phenolic compounds: A review. Current Research in Food Science, 4, 200-214. https://doi.org/10.1016/j.crfs.2021.03.011 DOI: https://doi.org/10.1016/j.crfs.2021.03.011

Albarri, O., Var, I., Boushihassal, A., Meral, M., Önlen, C., Mohamed, M., & Köksal, F. (2017). The potential effects of Pomegranate on Bacteria and Viruses: A review. Journal of Biotechnology Science Research, 3(6), 175-180.

Alharbi, M. H., Khormi, A. Y., Albisher, A. M., Barkoot, M. M., Alsofyani, B. A., Althabet, F. M., Almughamsi, R. A., Albalw, R. A. I., Alsari, S. M., & Aljehani, H. S. (2017). The dangerous effects of excessive use of antibiotics among community in Saudi Arabia. The Egyptian Journal of Hospital Medicine, 69(5), 2493-2496. https://doi.org/10.12816/0041700 DOI: https://doi.org/10.12816/0041700

AlMatar, M., Islam, M. R., Albarri, O., Var, I., & Koksal, F. (2018). Pomegranate as a possible treatment in reducing risk of developing wound healing, obesity, neurodegenerative disorders, and diabetes mellitus. Mini Reviews in Medicinal Chemistry, 18(6), 507-526. https://doi.org/10.2174/1389557517666170419114722 DOI: https://doi.org/10.2174/1389557517666170419114722

Arome, D., & Chinedu, E. (2013). The importance of toxicity testing. Journal of Pharmaceutical and BioSciences, 4, 146-148.

Borrelli, F., & Izzo, A. A. (2000). The plant kingdom as a source of anti‐ulcer remedies. Phytotherapy Research, 14(8), 581-591. https://doi.org/10.1002/1099-1573(200012)14:8%3C581::AID-PTR776%3E3.0.CO;2-S DOI: https://doi.org/10.1002/1099-1573(200012)14:8<581::AID-PTR776>3.0.CO;2-S

Chan, F. K., & Leung, W. (2002). Peptic-ulcer disease. The Lancet, 360(9337), 933-941. https://doi.org/10.1016/S0140-6736(02)11030-0 DOI: https://doi.org/10.1016/S0140-6736(02)11030-0

Dharmani, P., Mishra, P. K., Maurya, R., Chauhan, V. S., & Palit, G. (2005). Allophylus serratus: A plant with potential anti-ulcerogenic activity. Journal of Ethnopharmacology, 99(3), 361-366. https://doi.org/10.1016/j.jep.2005.01.011 DOI: https://doi.org/10.1016/j.jep.2005.01.011

Ebbo, A., Sani, D., Suleiman, M., Ahmad, A., & Hassan, A. (2020). Acute and sub-chronic toxicity evaluation of the crude methanolic extract of Diospyros mespiliformis hochst ex a. DC (Ebenaceae) and its fractions. Toxicology Reports, 7, 1138-1144. https://doi.org/10.1016/j.toxrep.2020.08.028 DOI: https://doi.org/10.1016/j.toxrep.2020.08.028

Ekor, M. (2014). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4, 66193. https://doi.org/10.3389/fphar.2013.00177 DOI: https://doi.org/10.3389/fphar.2013.00177

El Hilaly, J., Israili, Z. H., & Lyoussi, B. (2004). Acute and chronic toxicological studies of Ajuga iva in experimental animals. Journal of Ethnopharmacology, 91(1), 43-50. https://doi.org/10.1016/j.jep.2003.11.009 DOI: https://doi.org/10.1016/j.jep.2003.11.009

Erhirhie, E. O., Ihekwereme, C. P., & Ilodigwe, E. E. (2018). Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdisciplinary Toxicology, 11(1), 5-12. https://doi.org/10.2478/intox-2018-0001 DOI: https://doi.org/10.2478/intox-2018-0001

Erhirhie, E. O., Nneoma Okafor, J., Chinaecherem Nwafor, M., Ozioma Ajaegbo, C., & C Akunne, T. (2023). Toxicological Evaluations of a Popular Polyherbal Remedy-STC30 in Wistar Rats. Iranian Journal of Toxicology, 17(3), 1-9. http://dx.doi.org/10.61186/IJT.17.3.1 DOI: https://doi.org/10.61186/IJT.17.3.1

Farzamfar, B., Abdollahi, M., Kabinezhadian, S., Heshmat, R., Shah, H. M. H., Novitsky, Y., & Farhadi, M. (2008). Sub-chronic toxicity study of a novel herbal-based formulation (Semelil) on dogs. DARU Journal of Pharmaceutical Science, 16, 15-19.

Harborne, J. (1998). Phytochemical Methods: London Chapman and Halls.

Harris, E. H. (2005). Elevated liver function tests in type 2 diabetes. Clinical Diabetes, 23(3), 115-119. https://doi.org/10.2337/diaclin.23.3.115 DOI: https://doi.org/10.2337/diaclin.23.3.115

Hodges, R. E., & Minich, D. M. (2015). Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. Journal of Nutrition and Metabolism, 2015, 760689. https://doi.org/10.1155/2015/760689 DOI: https://doi.org/10.1155/2015/760689

Ifeoma, O., & Oluwakanyinsola, S. (2013). Screening of herbal medicines for potential toxicities. In S. Gowder (Ed.), New Insights into Toxicity and Drug Testing (Vol. 244, pp. 63-88): IntechOpen. https://doi.org/10.5772/54493 DOI: https://doi.org/10.5772/54493

Iqbal, S., Parray, S., Wadud, A., & Jahan, N. (2012). Concept of gastric ulcer (Qarhe medah) in Unani system of medicine: a review. International Journal of Industrial Pharmacy and Bio Sciences, 1, 132-143.

Jain, P. (2016). Secondary metabolites for antiulcer activity. Natural Product Research, 30(6), 640-656. https://doi.org/10.1080/14786419.2015.1036269 DOI: https://doi.org/10.1080/14786419.2015.1036269

Joshua, Z., & Timothy, A. (2011). Toxicity studies of the aqueous root extract of Lecaniodiscus cupanioides on albino rats. Science World Journal, 6(4), 27-29.

Keshavarzi, Z., Rezapour, T. M., Vatanchian, M., Hesari, M. Z., Haghighi, H. N., Izanlu, M., Sabaghian, M., & Shahveisi, K. (2014). The effects of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid-induced gastric ulcer in male rats. Avicenna Journal of Phytomedicine, 4(2), 137-143. https://doi.org/10.22038/ajp.2014.1909

Kim, D. O., Jeong, S. W., & Lee, C. Y. (2003). Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chemistry, 81(3), 321-326. https://doi.org/10.1016/S0308-8146(02)00423-5 DOI: https://doi.org/10.1016/S0308-8146(02)00423-5

Luna, L. G. (1968). Manual of histologic staining methods of the Armed Forces Institute of Pathology: McGraw-Hill.

Malfertheiner, P., Chan, F. K., & McColl, K. E. (2009). Peptic ulcer disease. The Lancet, 374(9699), 1449-1461. https://doi.org/10.1016/S0140-6736(09)60938-7 DOI: https://doi.org/10.1016/S0140-6736(09)60938-7

Moriya, M., Uehara, A., Okumura, T., Miyamoto, M., & Kohgo, Y. (2011). Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori eradication: two case reports. Journal of Medical Case Reports, 5, 252. https://doi.org/10.1186/1752-1947-5-252 DOI: https://doi.org/10.1186/1752-1947-5-252

Nafiu, M. O., Abdulsalam, T. A., & Akanji, M. A. (2013). Phytochemical analysis and antimalarial activity aqueous extract of Lecaniodiscus cupanioides root. Journal of Tropical Medicine, 2013, 605393. https://doi.org/10.1155/2013/605393 DOI: https://doi.org/10.1155/2013/605393

Nurudeen, Q., Salahudeen, T., Salimon, S., Ayinla, A., & Falana, M. (2021). Safety Evaluation of the Aqueous Extract of Lecaniodiscus cupanioides Roots in Male Wistar Rats. The Nexus (Science Edition), 1(1), 8-16.

Ojo, O., & Ndinteh, D. T. (2023). Traditional uses, biological activities, and phytochemicals of Lecaniodiscus cupanioides: a review. Physical Sciences Reviews, 8(4), 549-565. https://doi.org/10.1515/psr-2020-0207 DOI: https://doi.org/10.1515/psr-2020-0207

Olaniyan, J. M., Muhammad, H. L., Makun, H. A., Busari, M. B., & Abdullah, A. S. (2016). Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats. In M. Larramendy & S. Soloneski (Eds.), Toxicology: New Aspects to This Scientific Conundrum (Vol. 5, pp. 62-70): IntechOpen. DOI: https://doi.org/10.1016/j.joad.2015.08.006

Oloyede, A. M., Ottu, B., Ogunsanwo, A., Sobiye, S., Kehinde, B., Aromolaran, C., Ogidi, C., & Okafor, E. (2020). Subchronic Toxicity of the Ethanolic Extract of Lecaniodiscus cupanioides on Albino Wistar Mice (Mus musculus). Herbal Medicines Journal, 5(4), 145-152. https://doi.org/10.22087/hmj.v5i4.806

Parmar, N., & Desai, J. K. (1993). A review of the current methodology for the evaluation of gastric and duodenal anti-ulcer agents. Indian Journal of Pharmacology, 25(3), 120-135.

Périco, L. L., Heredia-Vieira, S. C., Beserra, F. P., de Cássia Dos Santos, R., Weiss, M. B., Resende, F. A., dos Santos Ramos, M. A., Bonifácio, B. V., Bauab, T. M., & Varanda, E. A. (2015). Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar.(Sapindaceae) in rats. Journal of Ethnopharmacology, 172, 312-324. https://doi.org/10.1016/j.jep.2015.06.025 DOI: https://doi.org/10.1016/j.jep.2015.06.025

Ramasubramaniaraja, R., & Babu, M. N. (2011). Peptic ulcer and phytochemistry: an overview. Journal of Pharmacy Research, 4(1), 156-160.

Roy, S. (2016). Clinical study of peptic ulcer disease. Asian Journal of Biomedical and Pharmaceutical Sciences, 6(53), 41-43.

Sam, S. (2019). Importance and effectiveness of herbal medicines. Journal of Pharmacognosy and Phytochemistry, 8(2), 354-357.

Sharma, R., Mandal, S., Rajani, G., Gupta, N., & Srivastava, D. (2011). Antiulcer and antiinflammatory activity of fresh leave extracts of Polyalthia longifolia in rats. International Journal of Drug Development & Research, 3(1), 351-359.

Sheen, E., & Triadafilopoulos, G. (2011). Adverse effects of long-term proton pump inhibitor therapy. Digestive Diseases and Sciences, 56, 931-950. https://doi.org/10.1007/s10620-010-1560-3 DOI: https://doi.org/10.1007/s10620-010-1560-3

Sofowora, A. (1993). Medicinal plants and traditional medicine in Africa. Ibadan: Nigeria: Spectrum Books Ltd.

Sonnenberg, A. (2013). Historic changes of Helicobacter pylori‐associated diseases. Alimentary Pharmacology & Therapeutics, 38(4), 329-342. https://doi.org/10.1111/apt.12380 DOI: https://doi.org/10.1111/apt.12380

Sumbul, S., Ahmad, M. A., Mohd, A., & Mohd, A. (2011). Role of phenolic compounds in peptic ulcer: An overview. Journal of Pharmacy and Bioallied Sciences, 3(3), 361-367. https://doi.org/10.4103/0975-7406.84437 DOI: https://doi.org/10.4103/0975-7406.84437

Thomas, S., Femeesh, M., Nafia, K., Siyad, M., & Shrikumar, S. (2005). Pharmacological review of anti ulcer screening. World Journal of Pharmaceutical Sciences, 6(5), 1369-1387. DOI: https://doi.org/10.20959/wjpps201705-9104

Trease, G. E. (2002). Pharmacognosy, 16th Edition, Brailliar Tiridel Can: Macmillian Publishers.

Udoudoh, P., Uti, D., Edet, E., Etukudoh, S., Ukwak, B., Obeten, U., & Umoru, G. (2020). Synergistic Antidiabetic Activity of Gongronema latifolium and Telfairia occidentalis Leaves Extracts on Hepatic Function and Hematological Indices in Wistar Rats. Sciences, 13(1), 42-52. DOI: https://doi.org/10.3923/ajbs.2020.42.52

Ugwah, M. O., Etuk, E. U., Bello, S. O., Aliero, A. A., & Ugwah-Oguejiofor, C. J. (2013). Comparative studies of anti-ulcerogenic activities of three Nigerian medicinal plants: a preliminary evaluation. Journal of Medicinal Plants Research, 7(9), 490-495. https://doi.org/10.5897/JMPR012.1018