Acute oral toxicity and safety assessment of Morus alba L. (Moraceae) methanol fruit extract in mice
Main Article Content
Keywords
acute oral toxicity, biochemical parameters, histopathology, Morus alba, methanol extract
Abstract
Mulberry or Morus alba fruits, belonging to the Moraceae family, are well recognized for their distinct taste and high nutritional content. Nevertheless, studies revealing the toxic effects of fruits are scanty. This study aimed to examine the adverse effects of methanolic fruit extract (MFME) derived from M. alba on mice following OECD 425 guidelines. The female Swiss albino mice were divided into two distinct categories. One group was designated as the control group (administered vehicle), while the other was assigned as the test group (administered 2000 mg/kg MFME orally). Subsequently, behavioral changes were monitored daily, and body weights, relative organ weights, and biochemical and hematological parameters were measured. Additionally, liver, kidney, heart, brain, and ovary assessments were conducted on the 14th day to detect any signs of toxicity. A histopathological investigation was conducted on the anesthetized animals’ vital organs (heart, liver, kidney, brain, and ovary). The study’s findings indicate that the oral administration of MFME did not result in any mortality. Additionally, no significant changes were seen in behavior, food and water intake, biochemical parameters, hematological investigations, and organ weights. Furthermore, the histological analysis revealed no notable pathological alterations in the separated essential organs of mice treated with MFME. The results of this study indicate that the oral administration of MFME is deemed safe up to the maximum test dosage of 2000 mg/kg.
References
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Guergour, H., Allouni, R., Mahdeb, N., Bouzidi, A. (2017) Acute and subacute toxicity evaluation of alkaloids of Peganum harmala L. in experimental mice. International Journal of Pharmacognosy and Phytochemical Research, 9:1182–1189. 10.25258/phyto.v9i09.10304
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Muthuraman, A., Singh, N. (2012) Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents. Asian Pacific Journal of Tropical Biomedicine, 2:S1017–S1023. 10.1016/S2221-1691(12)60354-2
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Organisation for Economic Co-operation and Development (OECD). (2008) Test No. 425: acute oral toxicity: up-and-down procedure. OECD publishing.
Polumackanycz, M., Sledzinski, T., Goyke, E., Wesolowski, M., Viapiana, A. (2019) A comparative study on the phenolic composition and biological activities of Morus alba L. commercial samples. Molecules, 24:3082. 10.3390/molecules24173082
Puri, V., Sharma, A., Kumar, P., Dua, K., Huanbutta, K., Singh, I., et al. (2022) Assessment of acute oral toxicity of thiolated gum ghatti in rats. Polymers, 14(18):3836. 10.3390/polym14183836
Saleem, U., Amin, S., Ahmad, B., Azeem, H., Anwar, F., Mary, S. (2017) Acute oral toxicity evaluation of aqueous ethanolic extract of Saccharum munja Roxb. roots in albino mice as per OECD 425 TG. Toxicology Reports, 4:580–585. 10.1016/j.toxrep.2017.10.005
Singh, V., Mujwar, S., Singh, M., Singh, T., Ahmad, S.F. (2023) Computational Studies to understand the neuroprotective mechanism of action basil compounds. Molecules, 28:7005. 10.3390/molecules28207005
Singh, V., Shri, R., Krishan, P., Singh, I.P., Shah, P. (2020) Isolation and characterization of components responsible for neuroprotective effects of Allium cepa outer scale extract against ischemia reperfusion induced cerebral injury in mice. Journal of Food Science, 85:4009–4017. 10.1111/1750-3841.15474
Singh, V., Krishan, P., Shri, R. (2018) Improvement of memory and neurological deficit with Ocimum basilicum L. extract after ischemia reperfusion induced cerebral injury in mice. Metabolic Brain Disease, 33:1111–1120. 10.1007/s11011-018-0215-5
Sood, P., Singh, V., Shri, R. (2023) Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment. Metabolic Brain Disease, 38:1657–1669. 10.1007/s11011-023-01199-2
Sood, P., Singh, V., Shri, R. (2024) Morus Alba Fruit Extract and its Fractions Ameliorate Streptozotocin Induced Cognitive Deficit in Mice via Modulating Oxidative and Cholinergic Systems. Neurochemical Research. 49:52–65. 10.1007/s11064-023-04009-4
Srivastava, S., Kapoor, R., Thathola, A., Srivastava, R.P. (2006) Nutritional quality of leaves of some genotypes of mulberry (Morus alba). International Journal of Food Sciences and Nutrition, 57:305–313. 10.1080/09637480600801837
Tabasum, S., Khare, S., Jain, K. (2016) Acute oral toxicity study of hydro-methanolic extract of Abrus precatorius l. seeds in wistar rats. International Journal of Pharmaceutical Sciences Review and Research, 38:155–158.
Vaghasiya, Y.K., Shukla, V.J., Chanda, S.V. (2011) Acute oral toxicity study of Pluchea arguta Boiss extract in mice. Journal of Pharmacology and Toxicology, 6:113–123. 10.3923/jpt.2011.113.123
Wattanathorn, J., Thukummee, W., Thipkaew, C., Wannanond, P., Tong-Un, T., Muchimapura, S., et al. (2012) Acute and subchronic toxicity of mulberry fruits. American Journal of Agricultural and Biological Sciences, 7:378–383. 10.3844/ajabssp.2012.378.383
Zainal, Z., Ong, A., Yuen May, C., Chang, S.K., Abdul Rahim, A., Khaza’ai, H. (2020) Acute and subchronic oral toxicity of oil palm puree in Sprague–Dawley rats. International Journal of Environmental Research and Public Health, 17(10):3404. 10.3390/ijerph17103404
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Zhang, H., Ma, Z.F., Luo, X., Li, X. (2018) Effects of mulberry fruit (Morus alba L.) consumption on health outcomes: a mini-review. Antioxidants, 7:69. 10.3390/antiox7050069
Zhang, J., Onakpoya, I.J., Posadzki, P., Eddouks, M. (2015). The safety of herbal medicine: from prejudice to evidence. Evidence-Based Complementary and Alternative Medicine, 2015, 316706. 10.1155/2015/316706
Bassan, A., Alves, V.M., Amberg, A., Anger, L.T., Beilke, L., Bender, A., et al. (2021) In silico approaches in organ toxicity hazard assessment: Current status and future needs for predicting heart, kidney and lung toxicities. Computational Toxicology, 20:100188. 10.1016/j.comtox.2021.100187
Bose, S., Datta, R., and Kirlin, W.G. (2021) Toxicity studies related to medicinal plants; in Mandal, S.C., Chakraborty, R., Sen, S. (eds.), Evidence based validation of traditional medicines, Singapore: Springer, pp. 621–647. 10.1007/978-981-15-8127-4_30
Daswani, G.P., Brijesh, S., Birdi, J.T. (2006) Preclinical testing of medicinal plants: advantages and approaches; in Workshop proceedings on approaches towards evaluation of medicinal plants prior to clinical trial. pp. 60–77.
Dhiman, S., Kumar, V., Mehta, C.M., Gat, Y., Kaur, S. (2020) Bioactive compounds, health benefits and utilisation of Morus spp.–a comprehensive review. The Journal of Horticultural Science and Biotechnology, 95(1):8–18. 10.1080/14620316.2019.1644969
Dybing, E., Doe, J., Groten, J., Kleiner, J., O’brien, J., Renwick, A.G., et al. (2020) Hazard characterisation of chemicals in food and diet: dose response, mechanisms and extrapolation issues. Food and Chemical Toxicology, 40(2–3):237–282. 10.1016/S0278-6915(01)00115-6
Ekor, M. (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4:177. 10.3389/fphar.2013.00177
Ercisli, S., Orhan, E. (2007) Chemical composition of white (Morus alba) red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chemistry, 103:1380–1384. 10.1016/j.foodchem.2006.10.054
Evans, W.C. (2009) Trease and Evans Pharmacognosy, 16th edn. Saunders: Elsevier; pp. 135–415. 10.1016/B978-0-7020-2933-2.00017-4
Gavanji, S. (2023) Cardiotoxicity effects of herbal medicine, a review article. Biology Medicine and Natural Product Chemistry, 12(1):89–96. 10.14421/biomedich.2023.121.89-96
Gong, S.X., Zhu, J.P. (2008) Mulberry relieving nutritional anemi. Journal of Traditional and Complementary Medicine, 32:350–352.
Guergour, H., Allouni, R., Mahdeb, N., Bouzidi, A. (2017) Acute and subacute toxicity evaluation of alkaloids of Peganum harmala L. in experimental mice. International Journal of Pharmacognosy and Phytochemical Research, 9:1182–1189. 10.25258/phyto.v9i09.10304
Hazarika, I., Geetha, K.M., Sundari, P.S., Madhu, D. (2019) Acute oral toxicity evaluation of extracts of Hydrocotyle sibthorpioides in wister albino rats as per OECD 425 TG. Toxicology Reports, 6:321–328. 10.1016/j.toxrep.2019.04.001
Kaur, A., Randhawa, K., Singh, V., Shri, R. (2019) Bioactivity guided isolation of acetylcholinesterase inhibitor from Ganoderma mediosinense (Agaricomycetes). International Journal of Medicinal Mushroom, 21:755–763. 10.1615/IntJMedMushrooms.2019031508
Kiliś-Pstrusińska, K., Wiela-Hojeńska, A. (2021) Nephrotoxicity of herbal Ppoducts in Europe—A review of an underestimated problem of nephrotoxicity of herbal products. International Journal of Molecular Sciences, 22:4132. 10.3390/ijms22084132
Ma, Z.T., Shi, Z., Xiao, X.H., Wang, J.B. (2023) New Insights into Herb-Induced Liver Injury. Antioxidants and Redox Signaling, 38:16–18. 10.1089/ars.2022.0134
Mansouri, A., Huusom, A.J., Hjortshøj, C. (2023) Neurotoxicity in a child after ingestion of star anise. Ugeskrift for Laeger 185:V06220370.
Moreira, D.D., Teixeira, S.S., Monteiro, M.H., De-Oliveira, A.C., Paumgartten, F.J. (2014) Traditional use and safety of herbal medicines. Revista Brasileira de Farmacognosia. 24(2):248–257. 10.1016/j.bjp.2014.03.006
Muthuraman, A., Singh, N. (2012) Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents. Asian Pacific Journal of Tropical Biomedicine, 2:S1017–S1023. 10.1016/S2221-1691(12)60354-2
Nasim, N., Sandeep, I.S., Mohanty, S. (2022) Plant-derived natural products for drug discovery: current approaches and prospects. Nucleus (Calcutta), 65(3):399–411. 10.1007/s13237-022-00405-3
Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., et al. (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology, 32:56–67. 10.1006/rtph.2000.1399
Organisation for Economic Co-operation and Development (OECD). (2008) Test No. 425: acute oral toxicity: up-and-down procedure. OECD publishing.
Polumackanycz, M., Sledzinski, T., Goyke, E., Wesolowski, M., Viapiana, A. (2019) A comparative study on the phenolic composition and biological activities of Morus alba L. commercial samples. Molecules, 24:3082. 10.3390/molecules24173082
Puri, V., Sharma, A., Kumar, P., Dua, K., Huanbutta, K., Singh, I., et al. (2022) Assessment of acute oral toxicity of thiolated gum ghatti in rats. Polymers, 14(18):3836. 10.3390/polym14183836
Saleem, U., Amin, S., Ahmad, B., Azeem, H., Anwar, F., Mary, S. (2017) Acute oral toxicity evaluation of aqueous ethanolic extract of Saccharum munja Roxb. roots in albino mice as per OECD 425 TG. Toxicology Reports, 4:580–585. 10.1016/j.toxrep.2017.10.005
Singh, V., Mujwar, S., Singh, M., Singh, T., Ahmad, S.F. (2023) Computational Studies to understand the neuroprotective mechanism of action basil compounds. Molecules, 28:7005. 10.3390/molecules28207005
Singh, V., Shri, R., Krishan, P., Singh, I.P., Shah, P. (2020) Isolation and characterization of components responsible for neuroprotective effects of Allium cepa outer scale extract against ischemia reperfusion induced cerebral injury in mice. Journal of Food Science, 85:4009–4017. 10.1111/1750-3841.15474
Singh, V., Krishan, P., Shri, R. (2018) Improvement of memory and neurological deficit with Ocimum basilicum L. extract after ischemia reperfusion induced cerebral injury in mice. Metabolic Brain Disease, 33:1111–1120. 10.1007/s11011-018-0215-5
Sood, P., Singh, V., Shri, R. (2023) Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment. Metabolic Brain Disease, 38:1657–1669. 10.1007/s11011-023-01199-2
Sood, P., Singh, V., Shri, R. (2024) Morus Alba Fruit Extract and its Fractions Ameliorate Streptozotocin Induced Cognitive Deficit in Mice via Modulating Oxidative and Cholinergic Systems. Neurochemical Research. 49:52–65. 10.1007/s11064-023-04009-4
Srivastava, S., Kapoor, R., Thathola, A., Srivastava, R.P. (2006) Nutritional quality of leaves of some genotypes of mulberry (Morus alba). International Journal of Food Sciences and Nutrition, 57:305–313. 10.1080/09637480600801837
Tabasum, S., Khare, S., Jain, K. (2016) Acute oral toxicity study of hydro-methanolic extract of Abrus precatorius l. seeds in wistar rats. International Journal of Pharmaceutical Sciences Review and Research, 38:155–158.
Vaghasiya, Y.K., Shukla, V.J., Chanda, S.V. (2011) Acute oral toxicity study of Pluchea arguta Boiss extract in mice. Journal of Pharmacology and Toxicology, 6:113–123. 10.3923/jpt.2011.113.123
Wattanathorn, J., Thukummee, W., Thipkaew, C., Wannanond, P., Tong-Un, T., Muchimapura, S., et al. (2012) Acute and subchronic toxicity of mulberry fruits. American Journal of Agricultural and Biological Sciences, 7:378–383. 10.3844/ajabssp.2012.378.383
Zainal, Z., Ong, A., Yuen May, C., Chang, S.K., Abdul Rahim, A., Khaza’ai, H. (2020) Acute and subchronic oral toxicity of oil palm puree in Sprague–Dawley rats. International Journal of Environmental Research and Public Health, 17(10):3404. 10.3390/ijerph17103404
Zarei, M.H., Lorigooini, Z., Khoei, H.A., Bijad, E. (2023) Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG. Toxicology Reports, 1(11):111:115. 10.1016/j.toxrep.2023.07.001
Zhang, H., Ma, Z.F., Luo, X., Li, X. (2018) Effects of mulberry fruit (Morus alba L.) consumption on health outcomes: a mini-review. Antioxidants, 7:69. 10.3390/antiox7050069
Zhang, J., Onakpoya, I.J., Posadzki, P., Eddouks, M. (2015). The safety of herbal medicine: from prejudice to evidence. Evidence-Based Complementary and Alternative Medicine, 2015, 316706. 10.1155/2015/316706
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Jul 1, 2024
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Sood, P., Shri, R., Singh, V., F. Ahmad, S., & M. Attia, S. (2024). Acute oral toxicity and safety assessment of Morus alba L. (Moraceae) methanol fruit extract in mice. Italian Journal of Food Science, 36(3), 11-19. https://doi.org/10.15586/ijfs.v36i3.2578
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How to Cite
Sood, P., Shri, R., Singh, V., F. Ahmad, S., & M. Attia, S. (2024). Acute oral toxicity and safety assessment of Morus alba L. (Moraceae) methanol fruit extract in mice. Italian Journal of Food Science, 36(3), 11-19. https://doi.org/10.15586/ijfs.v36i3.2578