{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:12:06Z","timestamp":1784347926308,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal University of Par\u00e1 (PROPESP, UFPA, Brazil)","award":["EDITAL 01\/2023\u2013PROPESP"],"award-info":[{"award-number":["EDITAL 01\/2023\u2013PROPESP"]}]},{"name":"Federal University of Par\u00e1 (PROPESP, UFPA, Brazil)","award":["PRO463-2017"],"award-info":[{"award-number":["PRO463-2017"]}]},{"DOI":"10.13039\/501100007382","name":"Funda\u00e7\u00e3o Amaz\u00f4nia de Amparo a Estudos e Pesquisas","doi-asserted-by":"publisher","award":["EDITAL 01\/2023\u2013PROPESP"],"award-info":[{"award-number":["EDITAL 01\/2023\u2013PROPESP"]}],"id":[{"id":"10.13039\/501100007382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007382","name":"Funda\u00e7\u00e3o Amaz\u00f4nia de Amparo a Estudos e Pesquisas","doi-asserted-by":"publisher","award":["PRO463-2017"],"award-info":[{"award-number":["PRO463-2017"]}],"id":[{"id":"10.13039\/501100007382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf\u2019s ethanolic extract is determined by ultra-performance liquid chromatography\u2013high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg\/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals\u2019 consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.<\/jats:p>","DOI":"10.3390\/ph16050689","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T01:36:38Z","timestamp":1683077798000},"page":"689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Margaritaria nobilis L.f. (Phyllanthaceae) Ethanolic Extract: Low Acute Oral Toxicity and Antinociceptive Activity"],"prefix":"10.3390","volume":"16","author":[{"given":"Fabiana Menezes S.","family":"Camara","sequence":"first","affiliation":[{"name":"Laboratory of Inflammation and Behavioral Pharmacology (Lafico), Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Costa","family":"da Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Behavioral Pharmacology (Lafico), Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise Karoline S.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Behavioral Pharmacology (Lafico), Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan Carlos C.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Laboratory of Liquid Chromatography (Labcrol), Exact and Natural Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto B.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Laboratory of Liquid Chromatography (Labcrol), Exact and Natural Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-8124","authenticated-orcid":false,"given":"Washington L.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Animal Pathology Laboratory, Amazon Federal Rural University, Bel\u00e9m 66077830, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-5650","authenticated-orcid":false,"given":"Marta C.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo Y.","family":"Yoshioka e Silva","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Laboratory of Liquid Chromatography (Labcrol), Exact and Natural Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-4058","authenticated-orcid":false,"given":"Milton Nascimento","family":"da Silva","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Laboratory of Liquid Chromatography (Labcrol), Exact and Natural Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4493-7375","authenticated-orcid":false,"given":"Cristiane F.","family":"Maia","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Behavioral Pharmacology (Lafico), Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-9581","authenticated-orcid":false,"given":"Eneas A.","family":"Fontes-Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation and Behavioral Pharmacology (Lafico), Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, Brazil"},{"name":"Pharmaceutical Sciences Post-Graduation Program, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075110, PA, 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