{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:16:56Z","timestamp":1791501416320,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universiti Kebangsaan Malaysia, Geran Galakan Penyelidikan Muda","award":["GGPM-2021-049"],"award-info":[{"award-number":["GGPM-2021-049"]}]},{"name":"Universiti Kebangsaan Malaysia, Geran Galakan Penyelidikan Muda","award":["RSP2023R111"],"award-info":[{"award-number":["RSP2023R111"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["GGPM-2021-049"],"award-info":[{"award-number":["GGPM-2021-049"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP2023R111"],"award-info":[{"award-number":["RSP2023R111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Annona muricata is a common plant used in Africa and South America to manage various types of disease. However, there is insufficient toxicological information or published standard available regarding repeated dose animal toxicity data. As part of the safety assessment, we exposed Sprague Dawley rats to an acute oral toxicity of A. muricata. The intent of the current study was to use advanced proton nuclear magnetic resonance (1H NMR) in serum and urinary metabolomics evaluation techniques to provide the in vivo acute toxicological profile of A. muricata leaf ethanol extract in accordance with the Organization for Economic Co-operation and Development\u2019s (OECD) 423 guidelines. A single 2000 mg\/kg dose of A. muricata leaf ethanol extract was administered to Sprague Dawley rats over an observational period of 14 days. The toxicity evaluation (physical and behavior observation, body weight, renal function test, liver function test and 1H NMR analysis) showed no abnormal toxicity. Histopathological analysis manifested mild changes, i.e., the treated kidney manifested mild hypercellularity of mesangial cells and mild red blood cell congestion. In addition, there was mild hemorrhage into tissue with scattered inflammatory cells and mild dilated central vein with fibrosis in the liver. However, the changes were very mild and not significant which correlate with other analyses conducted in this study (biochemical test and 1H NMR metabolomic analysis). On the other hand, urinary 1H NMR analysis collected on day 15 revealed high similarity on the metabolite variations for both untreated and treated groups. Importantly, the outcomes suggest that A. muricata leaf ethanol extract can be safely consumed at a dose of 2000 mg\/kg and the LD50 must be more than 2000 mg\/kg.<\/jats:p>","DOI":"10.3390\/toxics11080688","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:52:40Z","timestamp":1691664760000},"page":"688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Assessing the Acute Toxicological Effects of Annona muricata Leaf Ethanol Extract on Rats: Biochemical, Histopathological, and Metabolomics Analyses"],"prefix":"10.3390","volume":"11","author":[{"given":"Siti Norliyana","family":"Zubaidi","sequence":"first","affiliation":[{"name":"Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Kuala Lumpur 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim S. M.","family":"Qadi","sequence":"additional","affiliation":[{"name":"Department of Food Science, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Kuala Lumpur 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syahida","family":"Maarof","sequence":"additional","affiliation":[{"name":"Science and Food Technology Research Centre, Malaysian Agricultural Research and Development Institute, MARDI, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-9543","authenticated-orcid":false,"given":"Norazlan","family":"Mohmad Misnan","sequence":"additional","affiliation":[{"name":"Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam 40170, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halimatul Saadiah","family":"Mohammad Noor","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Management and Science University, University Drive Off Persiaran Olahraga, Section 13, Shah Alam 40100, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-5000","authenticated-orcid":false,"given":"Hamizah Shahirah","family":"Hamezah","sequence":"additional","affiliation":[{"name":"Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Kuala Lumpur 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-1224","authenticated-orcid":false,"given":"Syarul Nataqain","family":"Baharum","sequence":"additional","affiliation":[{"name":"Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Kuala Lumpur 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurwahyuna","family":"Rosli","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras 56000, Wilayah Persekutuan Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-8444","authenticated-orcid":false,"given":"Faidruz Azura","family":"Jam","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Manipal University College Malaysia (MUCM), Jalan Padang Jambu, Bukit Baru 75150, Melaka, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-9848","authenticated-orcid":false,"given":"Ebtesam","family":"Al-Olayan","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-115X","authenticated-orcid":false,"given":"Chuanyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Environmental Science and Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaoula","family":"Hellal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Mu\u011fla University, Mu\u011fla 48121, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-5507","authenticated-orcid":false,"given":"Nawal","family":"Buzgaia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Benghazi, Qar Yunis, Benghazi 5341, Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-1995","authenticated-orcid":false,"given":"Ahmed","family":"Mediani","sequence":"additional","affiliation":[{"name":"Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Kuala Lumpur 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","first-page":"115","article-title":"Evaluation of Acute and Subchronic Toxicity of Annona muricata (Linn.) 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