{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:30:49Z","timestamp":1779345049826,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,11]],"date-time":"2017-11-11T00:00:00Z","timestamp":1510358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Scorpions of the genus Tityus are responsible for the majority of envenomation in Brazil, the Tityus serrulatus species being the most common and dangerous in South America. In this approach, we have investigated the ability of the aqueous extract from the leaves of Aspidosperma pyrifolium in reducing carrageenan-induced inflammation and the inflammation induced by T. serrulatus envenomation in mice. We also evaluated the cytotoxic effects of this extract, using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl-2H-tetrazolium (MTT) assay and the results revealed that the extract is safe. Analysis by High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD) and Liquid Chromatography Coupled with Mass Spectrometry with Diode Array Detection (LC-DAD-MS) showed one major chemical component, the flavonoid rutin and phenolics compounds. For in vivo studies in carrageenan-induced peritonitis model, mice received extracts, dexamethasone, rutin or saline, before administration of carrageenan. For venom-induced inflammation model, animals received T. serrulatus venom and were, simultaneously, treated with extracts, antivenom, rutin or saline. The extract and rutin showed a reduction in the cell migration into the peritoneal cavity, and in the same way the envenomated animals also showed reduction of edema, inflammatory cell infiltration and vasodilation in lungs. This is an original study revealing the potential action of A. pyrifolium against inflammation caused by Tityus serrulatus venom and carrageenan, revealing that this extract and its bioactive molecules, specifically rutin, may present potential anti-inflammatory application.<\/jats:p>","DOI":"10.3390\/ijms18112248","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T11:12:36Z","timestamp":1510571556000},"page":"2248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Aspidosperma pyrifolium Has Anti-Inflammatory Properties: An Experimental Study in Mice with Peritonitis Induced by Tityus serrulatus Venom or Carrageenan"],"prefix":"10.3390","volume":"18","author":[{"given":"Ma\u00edra","family":"Souza Lima","sequence":"first","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Oliveira Bitencourt","sequence":"additional","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allanny","family":"Furtado","sequence":"additional","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-1533","authenticated-orcid":false,"given":"Manoela","family":"Torres-R\u00eago","sequence":"additional","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emerson","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy (PNBio), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Natural Biopolymers, Department of Biochemistry, Bioscience Center, Campus Universit\u00e1rio, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova 59072-970, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-1221","authenticated-orcid":false,"given":"Hugo","family":"Oliveira Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Natural Biopolymers, Department of Biochemistry, Bioscience Center, Campus Universit\u00e1rio, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova 59072-970, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyla","family":"Ferreira Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Departament of Pathology, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7516-1787","authenticated-orcid":false,"given":"Arn\u00f3bio","family":"Silva-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2768-0793","authenticated-orcid":false,"given":"Silvana","family":"Zucolotto","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy (PNBio), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus","family":"Fernandes-Pedrosa","sequence":"additional","affiliation":[{"name":"Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S\/N, Petr\u00f3polis 59012-570, Natal, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0041-0101(02)00145-9","article-title":"Sympathetic nervous system activation, antivenin administration and cardiovascular manifestations of scorpion envenomation","volume":"40","author":"Donis","year":"2002","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0041-0101(02)00208-8","article-title":"Increased plasma levels of IL-1 \u03b2, IL-6, IL-8, IL-10 and TNF-\u03b1 in patients moderately or severely envenomed by Tityus serrulatus scorpion sting","volume":"41","author":"Fukuhara","year":"2003","journal-title":"Toxicon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1590\/S0021-75572008000700007","article-title":"An\u00e1lise de vari\u00e1veis relacionadas \u00e0 evolu\u00e7\u00e3o letal do escorpionismo em crian\u00e7as e adolescentes no estado de Minas Gerais no per\u00edodo de 2001 a 2005","volume":"84","author":"Guerra","year":"2008","journal-title":"J. Pediatr. (Rio. J.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.etp.2011.08.010","article-title":"Tityus serrulatus venom increases vascular permeability in selected airway tissues in a mast cell-independent way","volume":"65","author":"Zuliani","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_5","first-page":"143","article-title":"Lung oedema induced by Tityus serrulatus scorpion venom in the rat","volume":"118","author":"Matos","year":"1997","journal-title":"Comp. Biochem. Physiol. Part C Pharmacol. Toxicol. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.toxicon.2013.06.021","article-title":"Another record of significant regional variation in toxicity of Tityus serrulatus venom in Brazil: A step towards understanding the possible role of sodium channel modulators","volume":"73","author":"Oliveira","year":"2013","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1590\/S0104-79302002000100002","article-title":"On scorpion envenoming syndrome: Problems of medical ethics and accountability in medical research in India","volume":"8","author":"Murthy","year":"2002","journal-title":"J. Venom. Anim. Toxins"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"903295","DOI":"10.1155\/2010\/903295","article-title":"Scorpion venom and the inflammatory response","volume":"2010","author":"Petricevich","year":"2010","journal-title":"Mediators Inflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.toxicon.2013.02.012","article-title":"Enzymatic properties of venoms from Brazilian scorpions of Tityus genus and the neutralisation potential of therapeutical antivenoms","volume":"69","author":"Venancio","year":"2013","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jep.2004.08.006","article-title":"Insulin-like effects of Bauhinia forficata aqueous extract upon Tityus serrulatus scorpion envenoming","volume":"95","author":"Vasconcelos","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jep.2013.03.022","article-title":"Anti-snake venom activities of ethanolic extract of fruits of Piper longum L. (Piperaceae) against Russell\u2019s viper venom: Characterization of piperine as active principle","volume":"147","author":"Shenoy","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Warrell, D.A., Williams, D.J., Jensen, S., Brown, N., Calvete, J.J., and Harrison, R.A. (2013). The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: The way forward. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002162"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"F\u00e9lix-Silva, J., Souza, T., Menezes, Y.A.S., Cabral, B., C\u00e2mara, R.B.G., Silva-Junior, A.A., Rocha, H.A.O., Rebecchi, I.M.M., Zucolotto, S.M., and Fernandes-Pedrosa, M.F. (2014). Aqueous leaf extract of Jatropha gossypiifolia L. (Euphorbiaceae) inhibits enzymatic and biological actions of Bothrops jararaca snake venom. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104952"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0378-8741(97)00138-4","article-title":"A survey from the literature of plants used to treat scorpion stings","volume":"60","author":"Hutt","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.jep.2014.03.060","article-title":"Ipomoea asarifolia neutralizes inflammation induced by Tityus serrulatus scorpion venom","volume":"153","author":"Lima","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bitencourt, M.A.O., Lima, M.C.J.S., Torres-R\u00eago, M., Fernandes, J.M., Silva-J\u00fanior, A.A., Tambourgi, D.V., Zucolotto, S.M., and Fernandes-Pedrosa, M.F. (2014). Neutralizing effects of Mimosa tenuiflora extracts against inflammation caused by Tityus serrulatus scorpion venom. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/378235"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11101-006-9044-y","article-title":"Isolation and characterisation of the monoterpenoid indole alkaloids of Aspidosperma pyrifolium","volume":"6","author":"Antheaume","year":"2007","journal-title":"Phytochem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.toxicon.2009.08.004","article-title":"Poisoning in goats by Aspidosperma pyrifolium Mart.: Biological and cytotoxic effects","volume":"55","year":"2010","journal-title":"Toxicon"},{"key":"ref_19","unstructured":"Koch, I., Rapini, A., Sim\u00f5es, A.O., Kinoshita, L.S., Spina, A.P., and Castello, A.C.D. (2017, June 06). Apocynaceae in Lista de Esp\u00e9cies da Flora do Brasil, Available online: http:\/\/floradobrasil.jbrj.gov.br\/jabot\/floradobrasil\/FB15551."},{"key":"ref_20","first-page":"575","article-title":"Evaluation of Anti-inflammatory activity of Ethanol Extract of Bark of Aspidosperma quebraco-blanco","volume":"6","author":"Kaur","year":"2013","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_21","first-page":"95","article-title":"Scholars Research Library","volume":"2","author":"Singh","year":"2010","journal-title":"Der Pharma Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/218627","article-title":"The antinociceptive and anti-inflammatory activities of Aspidosperma tomentosum (Apocynaceae)","volume":"2013","author":"Aquino","year":"2013","journal-title":"Sci. World J."},{"key":"ref_23","unstructured":"Harborne, J.B., and Baxter, H. (1999). The Handbook of Natural Flavonoids, John Wiley."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0031-6997(24)01472-8","article-title":"The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer","volume":"52","author":"Middleton","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_25","first-page":"371","article-title":"Flavonoids as medicinal agents: Recent advances","volume":"557","author":"Pathak","year":"1991","journal-title":"Fitoterapia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.etp.2010.03.005","article-title":"Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells","volume":"63","author":"Marcarini","year":"2011","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s12906-016-1259-x","article-title":"Anti-inflammatory activity of aqueous extract and bioactive compounds identified from the fruits of Hancornia speciosa Gomes (Apocynaceae)","volume":"16","author":"Furtado","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jep.2016.07.048","article-title":"Aqueous extract from Ipomoea asarifolia (Convolvulaceae) leaves and its phenolic compounds have anti-inflammatory activity in murine models of edema, peritonitis and air-pouch inflammation","volume":"192","author":"Furtado","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","unstructured":"Naegele, E. (2016). Determination of Chlorogenic Acid in Coffee Products According to DIN 10767, Agilent Technologies."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1055\/s-2006-962766","article-title":"Flavonoidglycoside acids from flowers of Arnica montana und Arnica chamissonis","volume":"53","author":"Merfort","year":"1987","journal-title":"Planta Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/S0031-9422(00)84061-3","article-title":"Alkaloids of Aspidosperma pyrifolium","volume":"22","author":"Craveiro","year":"1983","journal-title":"Phytochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jep.2011.04.073","article-title":"Antitumor effect of laticifer proteins of Himatanthus drasticus (Mart.) Plumel\u2014Apocynaceae","volume":"137","author":"Mousinho","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jep.2012.04.013","article-title":"Anti-inflammatory effect of triterpene 3\u03b2, 6\u03b2, 16\u03b2-trihydroxylup-20(29)-ene obtained from Combretum leprosum Mart & Eich in mice","volume":"142","author":"Lanznaster","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/ni1275","article-title":"Immune cell migration in inflammation: Present and future therapeutic targets","volume":"6","author":"Luster","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1211\/jpp.60.4.0010","article-title":"Anti-inflammatory effects of red pepper (Capsicum baccatum) on carrageenan- and antigen-induced inflammation","volume":"60","author":"Spiller","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jep.2014.02.051","article-title":"\u03b2 Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo","volume":"153","author":"Syam","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_37","first-page":"171","article-title":"A comparative study of the cellular, exudative and histological responses to carrageenan, dextran and zymosan in the mouse","volume":"13","author":"Dawson","year":"1991","journal-title":"Int. J. Tissue React."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.jep.2014.06.048","article-title":"Biomolecular evidence of anti-inflammatory effects by Clematis mandshurica Ruprecht root extract in rodent cells","volume":"155","author":"Lee","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1995-7645(13)60182-0","article-title":"Medicinal uses, phytochemistry and pharmacology of Picralima nitida (Apocynaceae) in tropical diseases: A review","volume":"7","author":"Erharuyi","year":"2014","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.toxicon.2014.06.022","article-title":"Clinical consequences of Tityus bahiensis and Tityus serrulatus scorpion stings in the region of Campinas, southeastern Brazil","volume":"89","author":"Bucaretchi","year":"2014","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0041-0101(98)00251-7","article-title":"Serum levels of cytokines in patients envenomed by Tityus serrulatus scorpion sting","volume":"37","author":"Pereira","year":"1999","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0031-9422(00)00235-1","article-title":"Advances in flavonoids research since 1992","volume":"55","author":"Harborne","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/jat.1547","article-title":"Evaluating the possible genotoxic, mutagenic and tumor cell proliferation-inhibition effects of a non-anticoagulant, but antithrombotic algal heterofucan","volume":"30","author":"Costa","year":"2010","journal-title":"J. Appl. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1567-5769(03)00078-X","article-title":"Time course of acute-phase response induced by Tityus serrulatus venom and TsTX-I in mice","volume":"3","author":"Pessini","year":"2003","journal-title":"Int. Immunopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2248\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:49:03Z","timestamp":1760208543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,11]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["ijms18112248"],"URL":"https:\/\/doi.org\/10.3390\/ijms18112248","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,11]]}}}