Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats

Authors

  • Adedoyin T. Agbabiaka Department of Medical Biochemistry, Faculty of Basic Medical Sciences
  • Adejuwon Adewale Adeneye Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja 100001, Lagos State, Nigeria.
  • Joseph A. Olagunju Department of Medical Biochemistry, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja 100001, Lagos State, Nigeria
  • Ikechukwu I. Okoye Department of Oral Pathology and Medicine, Faculty of Dentistry, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja 100001, Lagos State, Nigeria

DOI:

https://doi.org/10.22401/p5cw5g89

Keywords:

Annona muricata, Aqueous fruit extract, Oral toxicity testing, Hemato-biochemical endpoints, Histopathological endpoints, Wistar rats

Abstract

Annona muricata fruit (i.e. Soursoup or custard apple a tropical plant species known for its edible fruit) has been attributed  with numerous medicinal benefits (including antimicrobial, anti-inflammatory, anti-protozoan, antioxidant, anxiolytic, anti-stress, anti-ulcerogenic, wound healing, hepato-protective, anti-icteric, hepatoprotective, anticancer and antihyperglycemic activities) as well as some toxicological effects (neurotoxicity and neurodegeneration). Despite its ancestral use and wide applications in human health, scientific information on its oral safety remains scanty. In this study, the oral safety of 100 mg/kd/day, 200 mg/kg/day and 400 mg/kg/day of the aqueous fruit extract of Annona Muricata (AFAM) was evaluated in young adult, male and female white albino Wistar rats using standard acute and 42-days sub-chronic oral toxicity testing guidelines on anthropometric, bi°C hemical, hematological and histo-pathological endpoints. In addition, preliminary qualitative and quantitative analyses of AFAM were undertaken using standard pr°C edures. Results of the study showed that the estimated LD50 value for the acute oral toxicity study of AFAM calculated to be greater than 5 g/kg body weight/oral route although the testing was ass°C iated with transient but reversible behavioral toxicities. For its sub-chronic oral toxicity testing, AFAM treatment resulted in profound %weight gain, decreases in the serum triglycerides and very low density lipoprotein cholesterol and liver enzymes. Similarly, prolonged oral AFAM treatments caused significant decrease and increase in the differential neutrophils and platelet counts, respectively while the hist-opathological features of hepatic steatosis and renal tubule collapse in the AFAM-treated livers and kidneys, respectively suggested possible increased intrahepatic lipids biosynthesis and nephrotoxicity. The preliminary phyt°C hemical analyses of AFAM showed the presence and relative amount of flavonoids, alkaloids, tannin, glycosides, saponin, and reducing sugars while the Gas Chromatography-Mass spectroscopy showed the relative abundance of thirteen compounds. Composite analyses conducted on the extract showed the presence of carbohydrate (64.65%), protein (2.14%), moisture content (8.07%), ash value (6.73%), lipid (14.22%) and fiber (4.19%). Overall, the study suggested that the prolonged AFAM oral treatments could predispose to the development of fatty liver disease from de novo intrahepatic biosynthesis of triglycerides, nephrotoxicity and hematotoxicity. In conclusion, the results of this study showed that  prolonged consumption of AFAM should be with a great caution as it could pose serious health concerns.

References

Ekor, M. “The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety.” Front Pharmacol., 4: 177, 2013. https://doi.org/10.3389/fphar.2013.00177

Borse, S.P.; Singh, D.P.; Nivsarkar. M. “Understanding the relevance of herb-drug interaction studies with special f°C us on interplays: a prerequisite for integrative medicine.” Porto Biomed J., 4(2): e15, 2019. https://doi.org/10.1016/j.pbj.0000000000000015

Gurib-Fakim, A. “Medicinal plants: traditions of yesterday and drugs of tomorrow.” Mol Aspects Med., 27(1): 1-93, 2006. https://doi.org/10.1016/j.mam.2005.07.008

Mekonnen, A.B.; Mohammed, A.S.; Tefera, A.K. “Ethnobotanical study of traditional medicinal plants used to treat human and animal diseases in Sedie Muja District, South Gondar, Ethiopia.” Evid. Based Complement. Alternat. Med., 2022: 7328613, 2022. https://doi.org/10.1155/2022/7328613.

Schmidt, B.M. “Responsible use of medicinal plants for cosmetics.” Hortic. Sci., 47(8): 985-991, 2012. https://doi.org/10.21273/HORTSCI.47.8.985

Boukandou Mounanga, M.; Mewono, L.; Aboughe Angone, S. “Toxicity studies of medicinal plants used in sub-Saharan Africa.” J. Ethnopharmacol., 174: 618–627, 2015. https://doi.org/10.1016/j.jep.2015.06.005.

Sofowora, A.; Ogunbodode, E.; Onayade, A. “The role and place of medicinal plants in the strategies for disease prevention.” Afr. J. Complement. Altern. Med., 10(5): 210-229, 2013. https://doi.org/10.4314/ajtcam.v10i5.2.

Moreira, D.L.; Teixeira, S.S.; Monteiro, M.H.D.; De-Oliveira, A-C.A.X.; Paumgartten, F.J.R. “Traditional use and safety of herbal medicines.” Rev. Bras. Farmacogn., 24(2): 248-257, 2014. https://doi.org/10.1016/j.bjp.2014.03.006.

Asher, G.N.; Corbett, A.H.; Hawke, R.L. “Common herbal dietary supplement – drug interactions” Am Fam. Physician, 96(2): 101-107, 2017.

Izzo, A.A. “Interactions between herbs and conventional drugs: overview of the clinical data.” Med. Princ. Pract., 21: 404-428, 2012. https://doi.org/10.1159/000334488.

Rey, N.S. “ Efficacy and safety of medicinal plants.” J. Anal. Pharm. Res., 9(2): 99-100, 2018.

https://doi.org/10.1155/2022/1304839.

Adewole, S.O.; Caxton-Martins, E.A. “Morphological changes and hypoglycemic effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on pancreatic β-cells of streptozot°C in-treated diabetic rats.” Afr. J. Biomed. Res., 9: 173-187, 2006. https://doi.org/10.4314/ajbr.v9i3.48903.

Adewole, S.O.; Ojewole, J.A. “Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepat°C ytes of streptozot°C in-treated diabetic rats.” Afr. J. Trad. Complement. Altern. Med., 6(1): 30-41, 2008.

https://doi.org/10.4314/ajtcam.v6i1.57071.

Mishra, S.; Ahmad, S.; Kumar, N.; Sharma, B.K. “Annona muricata (the cancer killer): A review.” Glob. J. Pharm. Res., 2(1): 1613-1618, 2013. https://doi.org/10.3390/cancers14184539.

Moghadamtousi, S.Z.; Rouhollahi, E.; Hajrezaie, M.; Karimian, H.; Abdulla, M.A.; Kadir, H.A. “Annona muricata leaves accelerate wound healing in rats via involvement of hsp70 and antioxidant defense.” Int. J. Surg., 18: 110-117, 2015. https://doi.org/10.1016/j.ijsu.2015.03.026.

De Souza, R.; Benassi, E.; da Silva, R.R.; Afonso, S.; Scarminio, I.S. “Enhanced extraction yields and mobile phase separations by solvent mixtures for the analysis of metabolites in Annona muricata L. leaves.” J. Sep. Sci., 32: 4176-4185, 2009. https://doi.org/10.1002/jssc.200900375.

Olakunle, S.; Onyechi, O.; James, O. “Toxicity, anti-lipid peroxidation, in vitro and in vivo evaluation of antioxidant activity of Annona muricata ethanol stem bark extract.” Am. J. Life Sci., 2: 271-277, 2014. https://doi.org/10.11648/j.ajls.20140205.14.

Coria-Téllez, A.V.; Montalvo-Gónzalez, E.; Yahia, E.M.; Obledo-Vázquez, E.N. “Annona muricata: A comprehensive review on its traditional medicinal uses, phyt°C hemicals, pharmacological activities, mechanisms of action and toxicity.” Arab. J. Chem., 11(5): 662-691, 2018. https://doi.org/10.1016/j.arabjc.2016.01.004.

Aiyeloja, A.A.; Bello, O.A. “Ethnobotanical potentials of common herbs in Nigeria: A case study of Enugu.” Educ. Res. Rev., 1(1): 16-22, 2006.

Orwa, C.; Mutua, A.; Kindt, R.; Jamnadass, R.; Anthony, S. “Agroforestree Database: A tree reference and selection guide”. Version 4.0., 2009. http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp

Anaya Esparza, L.M.; Montalvo-González, E. “Bioactive compounds of Soursop (Annona muricata L.) fruit.” In Bioactive compounds in under-utilized fruits and nuts. Reference series in Phyt°C hemistry; Murthy, H. and Bapat, V., Eds; Springer: Cham., 2020. https://doi.org/10.1007/978-3-030-06120-3_8-1.

Patil, H.V.; Dhankani, M.A.; Dhankani, A.R. “A review on Marvel fruit: Annona muricata.” Med. Sci. Forum, 21: 26, 2023. https://doi.org/10.3390/ECB2023-14355.

Moghadamtousi, S.Z.; Fadaeinasab, M.; Nikzad, S.; Mohan, G.; Ali, H.M.; Kadir, H.A. “Annona muricata (Annonaceae): A review of its traditional uses, isolated acetogenins and biological activities.” Int. J. Mol. Sci., 16(7): 15625-15658, 2015. https://doi.org/10.3390/ijms160715625.

Adeyemi, D.O.; Komolafe, O.A.; Adewole, O.S.; Obuotor, E.M.; Adenowo, T.K. “Anti-hyperglycemic activities of Annona muricata (Linn).” Afr. J. Trad. Complement. Altern. Med., 6: 62-69, 2009. PMID: 20162043.

Agbai, E.O.; Mounmbegna, P.; Njoku, C.; Nwanegwo, C.; Awemu, G.; Iwuji, S. “Effect of Annona muricata seed extract on blood glucose, total and differential white cell count after repeated exposure to clozapine.” Res. Neurosci., 4(1): 10-15, 2015. https://doi.org/10.5923/j.neuroscience.20150401.02.

Ahalya, B.; Shankar, K.R.; Kiranmayi, G. “Exploration of anti-hyperglycemic and hypolipidemic activities of ethanolic extract of Annona muricata bark in alloxan induced diabetic rats.” Int. J. Pharm. Sci. Rev. Res., 25:21-27, 2014. https://api.semanticscholar.org/CorpusID:21824328.

Usunobun, U.; Okolie, P.N. “Effect of Annona muricata pre-treatment on liver synthetic ability, kidney function and hematological parameters in dimethylnitrosamine (DMN)-administered rats.” Int. J. Med., 4(1): 1-5, 2016. https://doi.org/10.14419/IJM.V4I1.5709.

Okoye, J.O.; Nwachukwu, D.; Natuanya, I.; Nwakulite, A.; Alozie, I.; Obi, P. “Anticholestasis and anti-sinusoidal congestion properties of aqueous extract of Annona muricata stem bark following acetaminophen induced toxicity.” Eur. J. Exp. Biol., 6: 1-8, 2016.

Padma, P.; Chansouria, J.; Khosa, R. “Effect of alcohol extract of Annona muricata on cold immobilization stress induced tissue lipid peroxidation.” Phytother. Res., 11: 326-327, 1997. https://doi.org/10.1002/(SICI)1099-1573(199706)11:4<326::AID-PTR94>3.0.CO;2-B

Nawwar, M.; Ayoub, N.; Hussein, S.; Hashim, A.; El-Sharawy, R.; Wende, K.; Harms, M.; Lindequist, U. “Flavonol triglycoside and investigation of the antioxidant and cell stimulating activities of Annona muricata.” Arch. Pharm. Res., 35(5): 761-767, 2012. https://doi.org/10.1007/s12272-012-0501-4.

Balderrama-Carmona, A.P.; Silva-Beltrán, N.P.; Gálvez-Ruiz, J.C.; Ruíz-Cruz, S.; Chaidez-Quiroz, C.; Morán-Palacio, E.F. “Antiviral, antioxidant, and antihemolytic effect of Annona muricata L. leaves extracts.” Plants (Basel), 9(12): 1650, 2020. https://doi.org/10.3390/plants9121650.

Vijayameena, C.; Subhashini, G.; Loganayagi, M.; Ramesh, B. “Phyt°C hemical screening and assessment of antibacterial activity for the bioactive compounds in Annona muricata.” Int. J. Curr. Microbiol. Appl. Sci., 2: 1-8, 2013.

Iyanda-Joel, W.O.; Ajetunmobi, O.B.; Chinedu, S.N.; Iweala, E.E.J.; Adegbite, O.S. “Phyt°C hemical, antioxidant and mit°C hondrial permeability transition studies on fruit-skin ethanol extract of Annona muricata.” J. Toxicol. 2019: 7607031, 2019. https://doi.org/10.1155/2019/7607031.

George, V.C.; Kumar, D.N.; Suresh, P.; Kumar, R.A. “Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts.” J. Food Sci. Technol., 52: 2328-2335, 2015. https://doi.org/10.1007/s13197-014-1289-7.

Jaramillo, M.; Arango, G.; Gonzalez, M.; Robledo, S.; Velez, I.D. “Cytotoxicity and antileishmanial activity of Annona muricata pericarp.” Fitoterapia, 271: 183-186, 2000.

https://doi.org/10.1016/s0367-326x(99)00138-0.

Ezirim, A.; Okachi, V.; James, A.; Adebeshi, O.; Ogunnowo, S.; Odeghe, O. “Induction of apoptosis in myelogenous leukemic k562 cells by ethanolic leaf extract of Annona muricata.” Indian J. Drug Discov., 2: 142-151, 2013.

Nwok°C ha, C.R.; Owu, D.U.; Gordon, A.; Thaxter, K.; McCalla, G.; Ozolua, R.I.; Young, L. “Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats.” Pharm. Biol., 50: 1436-1441, 2012. https://doi.org/10.3109/13880209.2012.684690.

Yaminy, R.T.; Gunasekaran, R.; Prithika, V.S.; Sreenikitha, K.; Bindhu, J. “Bio-fabrication and efficiency analysis of Annona muricata extract coated on bamboo fiber for wound healing application” J. Nat. Fibers, 20(2): 2245142, 2023. https://doi.org/10.1080/15440478.2023.2245142.

Somsak, V.; Polwiang, N.; Chachiyo, S. “In vivo antimalarial activity of Annona muricata leaf extract in mice infected with Plasmodium berghei.” J. Pathog., 2016: 3264070, 2016.

https://doi.org/10.1155/2016/3264070.

Nwonuma, C.O.; Balogun, E.A.; Gyebi, G.A. “Evaluation of antimalarial activity of ethanolic extract of Annona muricata L.: An in vivo and an in silico approach.” J. Evid. Based Complementary Altern. Med.., 2023: 28, 2023. https://doi.org/10.1177/2515690X231165104.

Mutakin, M.; Fauziati, R.; Fadhilah, F.N.; Zuhrotun, A.; Amalia, R.; Hadisaputri, Y.E. “Pharmacological activities of Soursop (Annona muricata Lin.).” Molecules, 27: 1201, 2022.

https://doi.org/10.3390/molecules27041201.

Ferreira, L.E.; Castro, P.M.N.; Chagas, A.C.S.; França, S.C.; Beleboni, R.O. “In vitro antihelmintic activity of aqueous leaf extract of Annona muricata L. (Annonaceae) against Haemonchus contortus from sheep.” Exp. Parasitol., 134(3): 327-332, 2013. https://doi.org/10.1016/j.exppara.2013.03.032.

Rady, I.; Bl°C h, M.B.; Chamcheu, R-C.N.; Mbeumi, S.B.; Anwar, M.R.; Mohamed, H.; Babatunde, A.S.; Kuiate, J-R.; Noubissi, F.K.; El Sayed, K.A.; Whitfield, G.K.; Chamcheu, J.C.. “Anticancer properties of Graviola (Annona muricata): A comprehensive mechanistic review.” Oxid. Med. Cell. Longev., 2018: 1826170, 2018. https://doi.org/10.1155/2018/1826170.

Prabhakaran, K.; Ramasamy, G.; Doraisamy, U.; Mannu, J.; Jayadeepa, R.K.; Murugesan, J.R.. “Polyketide natural products, acetogenins from graviola (Annona muricata L), its bi°C hemical, cytotoxic activity and various analyses through computational and bio-programming methods.” Curr. Pharm. Des., 22(34): 5204-5210, 2016. https://doi.org/10.2174/1381612822666160531163144.

Hamid, R.A.; Fong, C.P.; Ahmad, Z.; Hussain, M.K. “Antin°C iceptive and antiulcerogenic activities of the ethanolic extract of Annona muricata leaf.” Rev. Bras. Farmacogn., 22: 630-641, 2012.

https://doi.org/10.1590/S0102-695X2012005000001.

Yap, S. “Colon cancer reversed by phyto-nutritional therapy: a case study.” Int. J. Biotechnol. Wellness Ind., 2(3): 132-139, 2013.

Abdul Wahab, S.M.; Jatan, I.; Haque, M.A.; Arshad, L. “Exploring the leaves of Annona muricata L. as a source of potential anti-inflammatory and anticancer agents.” Front Pharmacol., 9: 661, 2018.

https://doi.org/10.3389/fphar.2018.00661.

Mutakin, M.; Fauziati, R.; Fadhilah, F.N.; Zuhrotun, A.; Amalia, R.; Hadisaputri, Y.E. “Pharmacological activities of Soursop (Annona muricata Lin.).” Molecules, 27(4): 1201, 2022.

https://doi.org/10.3390/molecules27041201.

Chang, F.R.; Wu, Y.C. “Novel cytotoxic Annonaceous acetogenins from Annona muricata.” J. Nat. Prod., 64: 925-931, 2001. https://doi.org/10.1021/np010035s.

Champy, P.; Melot, A.; Guérineau, V.; Gleye, C.; Fall, D.; Höglinger, G.; H°C qemiller, R. “Quantification of acetogenins in Annona muricata linked to atypical Parkinsonism in Guadeloupe.” Mov. Disord., 20: 1629-1633, 2005. https://doi.org/10.1002/mds.20632.

Champy, P.; Guérineau, V.; O. Laprévote, O. “MALDI-TOF MS Profiling of Annonaceous Acetogenins in Annona muricata products for human consumption.” Molecules, 14: 5235-5246, 2009. https://doi.org/10.3390/molecules14125235.

Escobar-Khondiker, M.; Hôllerhage, M.; Muriel, M.P.; Champy, P.; Bach, A.; Depienne, C.; Hôglinger, G. “Annonacin, a natural mit°C hondrial complex I inhibitor, causes Tau pathology in cultured neurons.” J. Neurosci., 27: 7827-7837, 2007. https://doi.org/10.1523/JNEUROSCI.1644-07.2007.

Hôllerhage, M.; Mstusch, A.; Champy, P.; Lombès, R.M.; Oertel, W.H.; Hôglinger, G.U. “Natural liphophilic inhibitors of mit°C hondrial complex I are candidate toxins for sporadic neurodegenerative taupathologies.” Exp. Neurol., 220: 133-142. 2009. https://doi.org/10.1016/j.expneurol.2009.08.004.

Coria-Téllez, A.V.; Montalvo-Gónzalez, E.; Yahia, E.M.; Obledo-Vázquez, E.N. “Annona muricata: A comprehensive review on its traditional medicinal uses, phyt°C hemicals, pharmacological activities, mechanisms of action and toxicity.” Arab. J. Chem., 11(5): 662-691, 2018. https://doi.org/10.1016/j.arabjc.2016.01.004.

Jamshidi-Kia, F.; Lorigooini, Z.; Amini-Khoei, H. “Medicinal plants: Past history and future perspective.” J. Herbmed. Pharmacol. 7(1): 1-7, 2018. https://doi.org/10.15171/jhp.2018.01.

Adeneye, A.A.; Adeyemi, O.O.; Agbaje, E.O.; Banjo, A.A.F. “Evaluation of the toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. in rodents.” Afr. J. Trad. Complement. Altern. Med., 7(4): 350-369, 2010. https://doi.org/10.4314/ajtcam.v7i4.56704.

Adeneye, A.A.; Ajagbonna, O.P.; Adeleke, T.I.; Bello, S.O. “Preliminary toxicity and phyt°C hemical studies of the stem bark aqueous extract of Musanga cecropioides in rats.” J. Ethnopharmacol., 105: 374-379, 2006. https://doi.org/10.1016/j.jep.2005.11.027.

Esfandiar, Z.; Hosseini-Esfahani, F.; Mirmiran, P.; Azizi, F. “Diet quality indices and the risk of type 2 diabetes in the Tehran Lipid and Glucose Study.” BMJ Open Diabetes Res. Care,10(5): e002818, 2022. https://doi.org/10.1136/bmjdrc-2022-002818.

Pękal, A.; Pyrzynska, K. “Evaluation of Aluminium complexation reaction for flavonoid content assay.” Food Anal. Methods, 2014; 7: 1776-1782, 2014. https://doi.org/10.1007/s12161-014-9814-x.

Kavitha-Chandran, C.I.; Indira, G. “Quantitative estimation of total phenolic, flavonoids, tannin and chlorophyll content of leaves of Strobilanthes kunthiana (Neelakurinji).” J. Med. Plants Stud., 4(4): 282-286, 2016.

Kurkin, V.A.; Shmygareva, A.A.; Ryazanova, T.K.; San’kov, A.N. “Quantitative determination of total anthraquinone glycosides in Cassia syrup preparation.” Pharm. Chem. J., 50: 691-694, 2017.

https://doi.org/10.1007/s111094-017-1513-7.

Mursaliyeva, V.K.; Sarsenbek, B.T.; Dzhakibaeva, G.T.; Mukhanov, T.M.; Mammadov, R. “Total content of saponins, phenols and flavonoids and antioxidant and antimicrobial activity of in vitro culture of All°C hrusa gypsophiloides (Regel) Schischk compared to wild plants. Plants (Basel), 12(20): 3521, 2023. https://doi.org/10.3390/plants12203521.

Harman-Ware, A.E.; Skyes, R.; Peter, G.F.; Davis, M. “Determination of terpenoid content in pine by organic solvent extraction and fast-GC analysis.” Front. Energy Res., 4(2016): 2, 2016.

https://www.frontiersin.org/article/10.3389/fenrg.2016.00002.

Rubiano-Buitrago, P.; Pradhan, S.; Paetz, C.; Rowland, H.M. “New structures, spectrometric quantification, and inhibitory properties of cardenolides from Asclepias curassavica seeds.” Molecule, 28(1): 105, 2023. https://doi.org/10.3390/molecules28010105.

Onimawo, I.A. “Proximate composition and selected physic°C hemical properties of the seed, pulp and oil of soursop (Annona muricata).” Plant Foods Hum. Nutr., 57(2): 165-171, 2002.

https://doi.org/10.1023/a:1015228231512.

Maehre, H.K.; Dalheim, L.; Edvinsen, G.K.; Elvevoll, E.O.; Jensen, J-I. “Protein determination – method matters.” Foods, 7(1): 5, 2018. https://doi.org/10.3390/foods7010005.

Kaid, F.; Alabsi, A.M.; Alafifi, N.; Ali-Saeed, R.; Al-koshab, M.A.; Ramanathan, A.; Ali, A.M. “Histological, bi°C hemical, and hematological effects of Goniothalamin on selective internal organs of male Sprague-Dawley rats.” J. Toxicol., 2019: 6493286, 2019. https://doi.org/10.1155/2019/6493286.

Gavamukulya, Y.; Abou-Elella, F.; Wamunyokoli, F.; El-Shemy, H.A. “GC-MS analysis of bioactive phyt°C hemicals present in ethanolic extracts of leaves of Annona muricata: A further evidence for its medicinal diversity.” Pharmacogn. J., 7(5): 300-304, 2015. https://doi.org/10.5530/pj.2015.5.9.

Agu, K.C.; Okolie, P.N. “Proximate composition, phyt°C hemical analysis, and in vitro antioxidant potentials of extracts of Annona muricata (Soursop).” Food Sci. Nutr., 5(5): 1029-1036, 2017.

https://doi.org/10.1002/fsn3.498.

Hasmila, I.; Natsir, H.; Soekamto, N.H. “Phyt°C hemical analysis and antioxidant activity of soursop leaf extract (Annona muricata Linn.).” J. Phys.: Conf. Ser. 1341: 032027, 2019.

https://doi.org/10.1088/1742-6596/1341/3/032027.

Onuah, C.L.; Chukwuma, C.C.; Ohanador, R.; Chukwu, C.N.; Iruolagbe, J. “Quantitative phyt°C hemical analysis of Annona muricata and Art°C arpus heterophyllus leaves using gas chromatography-flame ionization detector.” Trends Appl. Sci. Res. 14: 113-118, 2019.

https://scialert.net/abstract/?doi=tasr.2019.113.118.

Jothy, S.L.; Zakaria, Z.; Chen, Y.; Lau, Y.L.; Latha, L.Y.; Sasidharan, S. “Acute oral toxicity of methanolic seed extract of Cassia fistula in mice.” Molecules 16:5268-5282, 2011.

https://doi.org/10.3390/molecules16065268.

Omotosho, O.E.; Iheagwam, F.N.; Noiki, I.A.; Omini, J.J. “Comparative study on chemical composition and antioxidant activity of Annona muricata plant parts cultivated in Convenant University, Ota, Ogun State, Nigeria”. Curr. Res. Nutr. Food Sci., 6(3): 23, 2018.

http://dx.doi.org/10.12944/CRNFSJ.6.3.23.

Han, S.H., Nicholls, S.J., Sakuma, I., Zhao, D., Koh, K.K. “Hypertriglyceridemia and cardiovascular diseases: revisited.” Korean Circ. J., 46(2):135-144, 2016. https://doi.org/10.4070/kcj.2016.46.2.135.

Nordestgaard, B.G. “Triglyceride-rich lipoproteins and atherosclerotic disease: New insights from epidemiology, genetics, and biology.” Circ. Res., 118(4): 547-563, 2016.

https://doi.org/10.1161/CIRCRESAHA.115.306249.

Peng, J.; Ruan, G.; Li, X. “Hypertriglyceridemia and atherosclerosis.” Lipids Health Dis., 16: 233, 2017. https://doi.org/10.1186/s12944-017-0625-0.

Diaz, G.J. “Toxicosis by plant alkaloids in humans and animals in Colombia.” Toxins (Basel), 7(12): 5408-5416, 2015. https://doi.org/10.3390/toxins7124892.

Ohno, I. “Relationship between hyperuricemia and chronic kidney disease.” Nucleosides Nucleotides Nucleic acids, 30(12):1039-1044, 2011. https://doi.org/10.1590/2175-8239-JBN-2020-U002.

Oh, T.R.; Choi, H.S.; Kim, C.S.; Bae, E.H.; Ma, S.K.; Sung, S.A.; Kim, Y.S.; Oh, K.H.; Kim, S.W. “Hyperuricemia has increased risk of progression of chronic kidney disease: propensity score matching analysis from the KNOW-CKD Study.” Sci. Rep., 9: 6681, 2019.

Roncal-Jimenez, C.; Lanaspa, M.A,; Jensen, T.; Sanchez-Lozada, L.G.; Johnson, R.J. “Mechanism by which dehydration may lead to chronic kidney disease.” Ann Nutr Metab., 66(Suppl 3): 10-13, 2015. https://doi.org/10.1159/000381239.

Barman, Z.; Hasan, M.; Miah, R.; Mou, A.D.; Hafsa, J.M.; Trisha, A.D.; Mahmud, F.; Ali, N. “Ass°C iation between hyperuricemia and chronic kidney disease: a cross-sectional study in Bangladeshi adults.” BMC End°C r. Disord., 23(1): 45, 2023. https://doi.org/10.1186/s12902-023-01304-7.

Beecher, G.R. “Overview of dietary flavonoids: nomenclature, Occurrence and intake.” J. Nutr., 133(10): 3248S-3254S, 2003. https://doi.org/10.1093/jn/133.10.3248S.

Sung, J.E.; Choi, J.Y.; Kim, J.E.; Lee, H.A.; Yun, W.B.; Park, J.J.; Kim, H.R.; Song, B.R.; Kim, D.S.; Lee, C.Y.; Lee, H.S.; Lim, Y.; Hwang, D.Y. “Hepatotoxicity and nephrotoxicity of saponin-enriched extract of Asparagus Cochinchinensis in ICR mice.” Lab. Anim. Res., 33(2): 57-67, 2017.

https://doi.org/10.5625/lar.2017.33.2.57.

Adamczyk, B.; Simon, J.; Kitunen, V.; Adamczyk, S.; Smolander, A. “Tannins and their complex interaction with different organic nitrogen compounds and enzymes: old paradigms versus recent advances.” ChemistryOpen, 6(5): 610-614, 2017. https://doi.org/10.1002/open.201700113.

Steventon, C.A.; Raidal, S.R.; Quinn, J.C.; Peters, A. “Steroidal saponin toxicity in Eastern grey Kangaroos (Macropus giganteus): A novel clinicopathologic presentation of hepatogenous photosensitization.” J. Wildl. Dis. 54(3): 491-502, 2018. https://doi.org/10.7589/2017-03-066.

Awodele, O.; Ishola, I.O.; Ikumawoyi, V.O.; Akindele, A.J.; Akintonwa, A. “Toxicological evaluation of the lyophilized fruit juice extract of Annona muricata Linn. (Annonaceae) in rodents.” J. Basic Clin. Physiol. Pharmacol., 2013: 85, 2013. https://doi.org/10.1515/jbcpp-2013-0085.

Vehreschild, J.J. “Pneumonia and lung infiltrates in neutropenic patients: many stones unturned.” Ann. Am. Thorac. S°C ., 10(5): 493-495, 2013. https://doi.org/10.1513/AnnalsATS.201308-260ED.

Evans, S.E.; Ost, D.E. “Pneumonia in the neutropenic cancer patient.” Curr Opin Pulm Med., 21(3): 260-271, 2015. https://doi.org/10.1097/MCP.0000000000000156.

Seok, H.; Ko, J.H.; Peck, K.R.; Kim, J-Y.; Lee, J.H.; Park, G.E.; Cho, S.Y.; Kang, C-I.; Lee, N.Y.; Chung, D.R. “Treatment of community-onset pneumonia in neutropenic cancer patients: β-lactam monotherapy versus combination antibiotic regimens.” Pneumonia, 11: 2, 2019.

https://doi.org/10.1186/s41479-019-0061-1.

Evtushenko, V.A.; Vusik, M.V.; Karakeshisheva, M.B.; Pleshko, R.I.; Ermolaeva, L.A. “Characteristic of inflammatory infiltrate of gastric mucosa in patients with grade II-III gastric dysplasia and of stomach cancer.” Klin. Med. (Moskva), 86(11): 48-53, 2008.

Yoshikawa, T.; Naito, Y. “The role of neutrophils and inflammation in gastric mucosal injury.” Free Radic. Res., 33(6): 785-794, 2009. https://doi.org/10.1080/10715760000301301.

Midi, A.; Çelikel, Ç.A.; Kaya, H. “Russell Body” gastritis: A case report.” Turk. J. Path., 26(2): 159-161, 2010. https://doi.org/10.1590/S1676-24442012000100008.

Hu, Q.; Zhang, Y.; Zhang, X.; Fu, K. ”Gastric mucosa-ass°C iated lymphoid tissue lymphoma and Helicobacter pylori infection: a review of current diagnosis and management.” Biomark. Res., 4:15, 2016. https://doi.org/10.1186/s40364-016-0068-1.

Olagunju, J.A.; Okeowo, T.; Ahmed, M.F.; Olowookere, J.O. “Status of trace mineral elements in iron-protein diet-induced kwashiorkor in rats.” Nig. J. Pure Appl. Sci., 12: 494-500, 1997.

Kiani, A.K.; Dhuli, K.; Donato, K.; Aquilanti, B.; Velluti, V.; Matera, G.; Iaconelli, A.; Connelly, S.T.; Bellinato, F.; Gisondi, P.; Bertelli, M. “Main nutritional deficiencies.” J. Prev. Med. Hyg. 63(2 Suppl. 3): E93-E101, 2022. https://doi,org/10.15167/2421-4248/jpmh2022.63.2S3.2752.

Olagunju, J.A.; Adewolu, A.A.; Salami, W.O. “Iron and zinc distribution in various tissues of normal and kwashiorkor rats.” Nig. J. Nutr. Sci., 15: 16-20, 1994.

Benjamin, O.; Lappin, S.L. “Kwashiorkor.” In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507876.

May, T.; de la Haye, B.; Nord, G.; Klatt, K.; Stephenson, K.; Adams, S.; Bollinger, L.; Hanchard, N.; Arning, E.; Bottiglieri, T.; Maleta, K.; Manary, M.; Jahoor, F. “One-carbon metabolism in children with marasmus and kwashiorkor.” EBioMedicine, 75: 103791, 2022. https://doi.org/10.1016/j.ebiom.2021.103791. .

Downloads

Published

2024-03-15

Issue

Section

Articles

How to Cite

[1]
“Oral Safety Evaluation of the Aqueous Fruit Extract of Annona Muricata in Wistar Rats”, ANJS, vol. 27, no. 1, pp. 86–107, Mar. 2024, doi: 10.22401/p5cw5g89.