{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:28:22Z","timestamp":1764048502804,"version":"3.45.0"},"reference-count":102,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004911","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Piau\u00ed","doi-asserted-by":"publisher","award":["001\/2023"],"award-info":[{"award-number":["001\/2023"]}],"id":[{"id":"10.13039\/501100004911","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.jep.2025.120728","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:18:32Z","timestamp":1760109512000},"page":"120728","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"PB","title":["An antitumoral fraction with casearin-like diterpenes exhibits potent acute anti-inflammatory effectiveness and systemic subchronic toxicity"],"prefix":"10.1016","volume":"355","author":[{"given":"Denise Barbosa","family":"Santos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9bora Caroline do Nascimento","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia Amanda Cardoso de","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane Rodrigues","family":"Amorim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurandy do Nascimento","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhonatas Cley Santos","family":"Porto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Timah Acha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonielly Campinho","family":"dos Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Zalewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7296-7505","authenticated-orcid":false,"given":"J\u00falio Gabriel Sanches de","family":"Camargo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1vio Alexandre","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco de Assis","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Marcelo de","family":"Castro e Sousa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Gonzaga dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4276-3113","authenticated-orcid":false,"given":"M\u00e1rcia dos Santos","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-6497","authenticated-orcid":false,"given":"Paulo Michel Pinheiro","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2025.120728_bib1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.jep.2013.03.049","article-title":"Anti-inflammatory and antioxidant properties of hydroalcoholic crude extract from Casearia sylvestris Sw. (Salicaceae)","volume":"147","author":"Albano","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib2","series-title":"Argentina: Corpus Editorial Y Distribuidora","article-title":"Tratado de Fitof\u00e1rmacos y Nutrac\u00e9uticos","author":"Alonso","year":"2007"},{"key":"10.1016\/j.jep.2025.120728_bib3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10753-016-0496-y","article-title":"Physio-pharmacological investigations about the anti-inflammatory and antinociceptive efficacy of (+)-limonene epoxide","volume":"40","author":"Almeida","year":"2017","journal-title":"Inflammation"},{"key":"10.1016\/j.jep.2025.120728_bib4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jep.2015.08.027","article-title":"Toxicity study about a medicinal plant Casearia sylvestris: a contribution to the Brazilian unified health system (SUS)","volume":"175","author":"Ameni","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/15287394.2021.1881672","article-title":"Anti-inflammatory mechanisms of fruits and by-products from Mauritia flexuosa, an exotic plant with functional benefits","volume":"84","author":"Amorim","year":"2021","journal-title":"J. Toxicol. Environ. Health A Curr. Issues"},{"key":"10.1016\/j.jep.2025.120728_bib6","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1590\/0001-3765201520140288","article-title":"Antileishmanial activity of some Brazilian plants, with particular reference to Casearia sylvestris","volume":"87","author":"Antinarelli","year":"2015","journal-title":"An. Acad. Bras. Cienc."},{"key":"10.1016\/j.jep.2025.120728_bib7","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jep.2017.01.006","article-title":"Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors","volume":"198","author":"Ara\u00fajo","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib8","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1590\/0001-3765201520150149","article-title":"Counteracting effects on free radicals and histological alterations induced by a fraction with casearins","volume":"87","author":"Ara\u00fajo","year":"2015","journal-title":"An. Acad. Bras. Cienc."},{"key":"10.1016\/j.jep.2025.120728_bib9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0003-3472(73)80065-X","article-title":"Tests for emotionality in rats and mice: a review","volume":"21","author":"Archer","year":"1973","journal-title":"Anim. Behav."},{"key":"10.1016\/j.jep.2025.120728_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118393","article-title":"Casearia sylvestris var. lingua (C\u00e0mbess.) Eichler leaves aqueous extract improves colon inflammation through mucogenic, antioxidant and anti-inflammatory actions in TNBS- induced IBD rats","volume":"332","author":"Arunachalam","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jep.2025.120728_bib12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0378-8741(90)90007-G","article-title":"Pharmacological assay of Casearia sylvestris. I: preventive anti-ulcer activity and toxicity of the leaf crude extract","volume":"30","author":"Basile","year":"1990","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib13","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1590\/S0103-84782012000600020","article-title":"Plant poisonings in ruminants and horses in Southern Cear\u00e1, Northeastern Brazil","volume":"42","author":"Bezerra","year":"2012","journal-title":"Ci\u00eancia Rural."},{"key":"10.1016\/j.jep.2025.120728_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2020.114147","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective","volume":"180","author":"Bindu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0305-0491(00)00237-6","article-title":"Effects of aqueous extract of Casearia sylvestris (Flacourtiaceae) on actions of snake and bee venoms and on activity of phospholipases A2","volume":"127","author":"Borges","year":"2000","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"10.1016\/j.jep.2025.120728_bib16","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/S0041-0101(01)00169-6","article-title":"Neutralization of proteases from Bothrops snake venoms by the aqueous extract from Casearia sylvestris (Flacourtiaceae)","volume":"39","author":"Borges","year":"2001","journal-title":"Toxicon"},{"key":"10.1016\/j.jep.2025.120728_bib17","doi-asserted-by":"crossref","first-page":"9477","DOI":"10.3390\/molecules18089477","article-title":"Chemical composition and cytotoxicity evaluation of essential oil from leaves of Casearia sylvestris, its main compound \u03b1-zingiberene and derivatives","volume":"18","author":"Bou","year":"2013","journal-title":"Molecules"},{"key":"10.1016\/j.jep.2025.120728_bib18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jep.2014.04.019","article-title":"Cardiovascular protective effects of Casearia sylvestris Swartz in Swiss and C57BL\/6 LDLr-null mice undergoing high fat diet","volume":"154","author":"Brant","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib20","first-page":"123","article-title":"Presidency of the republic general secretary. Sub-office for legal affairs","volume":"13","year":"2015","journal-title":"Law n\u00b0"},{"key":"10.1016\/j.jep.2025.120728_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e39488","article-title":"Seasonal and circadian rhythms of clerodane diterpenes and glycosylated flavonoids in two varieties of Casearia sylvestris Sw. (Salicaceae)","volume":"10","author":"Bueno","year":"2024","journal-title":"Heliyon"},{"key":"10.1016\/j.jep.2025.120728_bib22","article-title":"Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders","volume":"14","author":"Caldito","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jep.2025.120728_bib24","article-title":"Medicina popular: aspectos metodol\u00f3gicos para pesquisa, garrafada, objeto de pesquisa, componentes medicinais de origem vegetal, animal e mineral","author":"Camargo","year":"1985","journal-title":"S\u00e3o Paulo: ALMED"},{"key":"10.1016\/j.jep.2025.120728_bib25","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s13104-015-1251-4","article-title":"Healing activity of Casearia sylvestris Sw. in second-degree scald burns in rodents","volume":"8","author":"Campos","year":"2015","journal-title":"BMC Res. Notes"},{"key":"10.1016\/j.jep.2025.120728_bib26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bjp.2017.10.007","article-title":"Natural membranes of Hevea brasiliensis latex as delivery system for Casearia sylvestris leaf components","volume":"28","author":"Carvalho","year":"2018","journal-title":"Rev Bras Farmacogn"},{"key":"10.1016\/j.jep.2025.120728_bib27","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jep.2007.04.002","article-title":"Neutralization of snake venom phospholipase A2 toxins by aqueous extract of Casearia sylvestris (Flacourtiaceae) in mouse neuromuscular preparation","volume":"112","author":"Cavalcante","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib28","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.3390\/cells13221906","article-title":"Inflammation: the cause of all diseases","volume":"13","author":"Chavda","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.jep.2025.120728_bib29","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.jep.2025.120728_bib30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1590\/S0085-56262009000300020","article-title":"Effect of Cerrado plant extracts on Dipetalogaster maxima (Uhler) (Hemiptera, Reduviidae)","volume":"53","author":"Coelho","year":"2009","journal-title":"Rev. Bras. Entomol."},{"issue":"142","key":"10.1016\/j.jep.2025.120728_bib31","doi-asserted-by":"crossref","first-page":"13590","DOI":"10.4414\/smw.2012.13590","article-title":"Interleukin-1, inflammasomes, autoinflammation and the skin","volume":"31","author":"Contassot","year":"2012","journal-title":"Swiss Med. Wkly."},{"key":"10.1016\/j.jep.2025.120728_bib32","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1476-5381.1990.tb12724.x","article-title":"Kinins and peritoneal exudates induced by carrageenin and zymosan in rats","volume":"101","author":"Damas","year":"1990","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib33","doi-asserted-by":"crossref","first-page":"69","DOI":"10.70151\/zgz15155","article-title":"Data of medicinal plants commonly used in the city of S\u00e3o Jo\u00e3o do Pol\u00easine, RS, Brazil. Relationship between illness and use of species","volume":"4","author":"Dorigoni","year":"2001","journal-title":"Rev. Bras. Plantas Med."},{"key":"10.1016\/j.jep.2025.120728_bib34","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.intimp.2018.06.031","article-title":"Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide","volume":"62","author":"Dornelas-Filho","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.ocarto.2024.100438","article-title":"Does sex affect the efficacy of systemic pharmacological treatments of pain in knee osteoarthritis? A systematic review","volume":"6","author":"Espinosa-Salas","year":"2024","journal-title":"Osteoarthr Cartil Open"},{"key":"10.1016\/j.jep.2025.120728_bib36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1590\/1983-084X\/13_074","article-title":"Ethanolic extract of Casearia sylvestris Sw exhibits In vitro antioxidant and antimicrobial activities and in vivo hypolipidemic effect in rats","volume":"17","author":"Espinosa","year":"2015","journal-title":"Rev. Bras. Plantas Med."},{"key":"10.1016\/j.jep.2025.120728_bib37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jep.2005.04.020","article-title":"Gastric antiulcer and anti-inflammatory activities of the essential oil from Casearia sylvestris Sw","volume":"101","author":"Esteves","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib38","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1016\/j.jep.2014.07.040","article-title":"Inhibition of tumor proliferation associated with cell cycle arrest caused by extract and fraction from Casearia sylvestris (Salicaceae)","volume":"155","author":"Felipe","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib39","doi-asserted-by":"crossref","DOI":"10.1172\/JCI180076","article-title":"Mechanisms underlying sex differences in autoimmunity","volume":"134","author":"Fairweather","year":"2024","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.jep.2025.120728_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.fitote.2023.105624","article-title":"Cordia oncocalyx and oncocalyxones: from the phytochemistry to the anticancer action and therapeutic benefits against chronic diseases","volume":"169","author":"Ferreira","year":"2023","journal-title":"Fitoterapia"},{"key":"10.1016\/j.jep.2025.120728_bib41","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jep.2016.04.011","article-title":"Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations","volume":"186","author":"Ferreira","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cbi.2014.10.015","article-title":"Morphological and biochemical alterations activated by antitumor clerodane diterpenes","volume":"222","author":"Ferreira","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.jep.2025.120728_bib43","doi-asserted-by":"crossref","DOI":"10.1590\/s2175-97902017000216076","article-title":"Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: new evidences and old challenges","volume":"53","author":"Ferreira","year":"2017","journal-title":"Braz J Pharm Sci"},{"key":"10.1016\/j.jep.2025.120728_bib44","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cbi.2010.08.008","article-title":"Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis","volume":"188","author":"Ferreira","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.jep.2025.120728_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2019.112004","article-title":"Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian unified health system (SUS)","volume":"241","author":"Ferreira","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib46","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1590\/S0103-84782010000200013","article-title":"Casearia sylvestris on gastric permeability to sucrose in horses submitted to gastric ulcer induction protocol","volume":"40","author":"Fialho","year":"2010","journal-title":"Ci\u00eancia Rural."},{"key":"10.1016\/j.jep.2025.120728_bib47","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1590\/S0102-695X2009000500018","article-title":"Protease inhibition activity of extracts from Salicaceae species from Brazilian Cerrado and Atlantic Rain Forest and of an enriched fraction of clerodane diterpenes (casearins)","volume":"19","author":"Flausino","year":"2009","journal-title":"Rev Bras Farmacogn"},{"key":"10.1016\/j.jep.2025.120728_bib48","first-page":"1103","article-title":"Participation of TNF-alpha and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis","volume":"28","author":"Gomes","year":"1995","journal-title":"Braz. J. Med. Biol. Res."},{"key":"10.1016\/j.jep.2025.120728_bib49","doi-asserted-by":"crossref","first-page":"8383","DOI":"10.1007\/s00210-024-03205-5","article-title":"Inflammation as a shared mechanism of chronic stress related disorders with potential novel therapeutic targets","volume":"397","author":"Gupta","year":"2024","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"},{"key":"10.1016\/j.jep.2025.120728_bib50","first-page":"821","article-title":"Adverse effects of nonsteroidal anti-inflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications","volume":"16","author":"Harirforoosh","year":"2014","journal-title":"J. Pharm. Pharmaceut. Sci."},{"key":"10.1016\/j.jep.2025.120728_bib51","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0027-5107(73)90035-3","article-title":"A rapid in vivo test for chromosomal damage","volume":"18","author":"Heddle","year":"1973","journal-title":"Mutat. Res."},{"key":"10.1016\/j.jep.2025.120728_bib52","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113139","article-title":"Macroscopic, biochemical and hystological evaluation of topical anti-inflammatory activity of Casearia sylvestris (Flacourtiaceae) in mice","volume":"264","author":"Heymanns","year":"2021","journal-title":"J. Ethnopharmacol."},{"year":"1939","series-title":"Plantas E Subst\u00e2ncias Vegetais T\u00f3xicas E Medicinais","author":"Hoehne","key":"10.1016\/j.jep.2025.120728_bib53"},{"key":"10.1016\/j.jep.2025.120728_bib54","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ymeth.2007.01.003","article-title":"The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity","volume":"42","author":"Houghton","year":"2007","journal-title":"Methods"},{"key":"10.1016\/j.jep.2025.120728_bib55","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.3390\/ijms20236008","article-title":"Cytokines in inflammatory disease","volume":"20","author":"Kany","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jep.2025.120728_bib56","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10565-006-0078-0","article-title":"Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation","volume":"23","author":"Korkmaz","year":"2007","journal-title":"Cell Biol. Toxicol."},{"key":"10.1016\/j.jep.2025.120728_bib57","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1177\/0192623310364025","article-title":"Early toxicology signal generation in the mouse","volume":"38","author":"Kramer","year":"2010","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.jep.2025.120728_bib58","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jep.2012.10.019","article-title":"Subchronic oral toxicity studies of the traditional herbal formula Bangpungtongseong-san in Crl: CD (SD) rats","volume":"144","author":"Lee","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib59","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.2147\/JIR.S509931","article-title":"Mast cells promote inflammatory th17 cells and impair treg cells through an IL-1\u03b2 and PGE2 axis","volume":"18","author":"Leveque","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"10.1016\/j.jep.2025.120728_bib60","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and aging: signaling pathways and intervention therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.jep.2025.120728_bib61","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1089\/neu.2005.22.885","article-title":"Effect of interleukin-1 on traumatic brain injury\u2013induced damage to hippocampal neurons","volume":"22","author":"Lu","year":"2005","journal-title":"J. Neurotrauma"},{"key":"10.1016\/j.jep.2025.120728_bib62","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00280-010-1392-z","article-title":"Cyclooxygenase-2 contributes to functional changes seen on experimental hemorrhagic cystitis induced by ifosfamide in rat urinary bladder","volume":"67","author":"Macedo","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib63","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-65821-8","article-title":"Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients","volume":"14","author":"Malik","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2025.120728_bib64","first-page":"551","article-title":"Casearia sylvestris improved cutaneous burn repair in diabetic rats","volume":"6","author":"Martelli","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib65","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.fitote.2004.01.014","article-title":"In vitro antioxidant activity of species collected in Paran\u00e1","volume":"75","author":"Menezes","year":"2004","journal-title":"Fitoterapia"},{"key":"10.1016\/j.jep.2025.120728_bib66","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1007\/s00204-019-02589-1","article-title":"Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: chloroacetaldehyde's contribution to urothelial dysfunction In vitro","volume":"93","author":"Mills","year":"2019","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.jep.2025.120728_bib67","first-page":"115","article-title":"Carrageenan-induced paw edema in the rat and mouse","volume":"225","author":"Morris","year":"2003","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.jep.2025.120728_bib68","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1056\/NEJMoa1611593","article-title":"Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis","volume":"375","author":"Nissen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jep.2025.120728_bib69","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1590\/0101-60830000000153","article-title":"Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics \u2013 a review","volume":"45","author":"Nunes","year":"2018","journal-title":"Arc Clin Psychiatr"},{"key":"10.1016\/j.jep.2025.120728_bib70","doi-asserted-by":"crossref","DOI":"10.1016\/j.fitote.2019.104197","article-title":"Acidic and hepatic derivatives of bioactive clerodane diterpenes casearins J and O","volume":"137","author":"Oda","year":"2019","journal-title":"Fitoterapia"},{"key":"10.1016\/j.jep.2025.120728_bib71","series-title":"OECD","first-page":"1","article-title":"Guidelines for testing of chemical, guideline 407","year":"2008"},{"key":"10.1016\/j.jep.2025.120728_bib72","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.107879","article-title":"Resolution of inflammation: an organizing principle in biology and medicine","volume":"227","author":"Panigrahy","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.jep.2025.120728_bib73","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1590\/0001-3765201720170339","article-title":"Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw","volume":"89","author":"Pereira","year":"2017","journal-title":"An. Acad. Bras. Cienc."},{"key":"10.1016\/j.jep.2025.120728_bib74","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bjp.2016.12.008","article-title":"Anti-inflammatory action of ethanolic extract and clerodane diterpenes from Casearia sylvestris","volume":"27","author":"Pierri","year":"2017","journal-title":"Rev Bras Farmacog"},{"key":"10.1016\/j.jep.2025.120728_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2021.115497","article-title":"\u03b1-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain","volume":"418","author":"Pinheiro-Neto","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jep.2017.03.059","article-title":"Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways","volume":"204","author":"Piovezan","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib77","first-page":"60","article-title":"Inflammatory mediators related to arthrogenic temporomandibular dysfunctions","volume":"1","author":"Poluha","year":"2018","journal-title":"Br. J. Pain"},{"key":"10.1016\/j.jep.2025.120728_bib78","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-1-4939-7113-8_14","article-title":"Detection of infiltrating mast cells using a modified toluidine blue staining","volume":"1627","author":"Puebla-Osorio","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.jep.2025.120728_bib79","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12906-019-2717-z","article-title":"Antimicrobial and antibiofilm activities of Casearia sylvestris extracts from distinct Brazilian biomes against Streptococcus mutans and Candida albicans","volume":"19","author":"Ribeiro","year":"2019","journal-title":"BMC Compl. Alternative Med."},{"key":"10.1016\/j.jep.2025.120728_bib80","doi-asserted-by":"crossref","first-page":"5403","DOI":"10.55905\/rdelosv18.n68-029","article-title":"Effect of pretreatment and extraction method to obtain bioactive compounds from Casearia sylvestris leaves","volume":"18","author":"Ricardo","year":"2025","journal-title":"Rev Delos"},{"key":"10.1016\/j.jep.2025.120728_bib81","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s10787-024-01605-w","article-title":"Repositioning anthelmintics for the treatment of inflammatory-based pathological conditions","volume":"33","author":"Rodrigues","year":"2025","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.jep.2025.120728_bib82","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1590\/S0074-02761991000600046","article-title":"Pharmacological screening of plants recommended by folk medicine as anti-snake venom: I. Analgesic and anti-inflammatory activities","volume":"86","author":"Ruppelt","year":"1991","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"10.1016\/j.jep.2025.120728_bib83","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1093\/jjco\/hyw093","article-title":"A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors","volume":"46","author":"Saito","year":"2016","journal-title":"Jpn. J. Clin. Oncol."},{"key":"10.1016\/j.jep.2025.120728_bib84","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/cbdv.200800342","article-title":"Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumor human cells","volume":"7","author":"Santos","year":"2010","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.jep.2025.120728_bib85","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1590\/S0100-40422007000500009","article-title":"Clerodane diterpenes from leaves of Casearia sylvestris Swartz","volume":"30","author":"Santos","year":"2007","journal-title":"Quim. Nova"},{"key":"10.1016\/j.jep.2025.120728_bib86","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1590\/S0102-86502004000600010","article-title":"Effect of Casearia sylvestris on bone repair with devitalized bovine bone matrix in rats","volume":"19","author":"Sassioto","year":"2004","journal-title":"Acta Cir. Bras."},{"key":"10.1016\/j.jep.2025.120728_bib87","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0165-1161(75)90058-8","article-title":"The micronucleus test","volume":"31","author":"Schmid","year":"1975","journal-title":"Mutat. Res."},{"key":"10.1016\/j.jep.2025.120728_bib88","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11010-006-9180-0","article-title":"The effect of Na+-K+ ATPase inhibition by ouabain on histamine release from human cutaneous mast cells","volume":"294","author":"Senol","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.jep.2025.120728_bib89","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1177\/002215540104900801","article-title":"Antigen retrieval techniques: current perspectives","volume":"49","author":"Shi","year":"2001","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.jep.2025.120728_bib90","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3390\/ph17050633","article-title":"Promising effects of casearins in tumor-bearing mice and antinociceptive action against oncologic pain: molecular docking and In vivo findings","volume":"17","author":"Silva","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.jep.2025.120728_bib91","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/13880200801887963","article-title":"Antimicrobial activity of ethanol extract from leaves of Casearia sylvestris","volume":"46","author":"Silva","year":"2008","journal-title":"Pharm. Biol."},{"key":"10.1016\/j.jep.2025.120728_bib92","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2174\/1874210601913010332","article-title":"The role of TNF-\u03b1 as a proinflammatory cytokine in pathological processes","volume":"13","author":"Silva","year":"2019","journal-title":"Open Dent. J."},{"key":"10.1016\/j.jep.2025.120728_bib93","article-title":"Effects of non-steroidal anti-inflammatory drugs (NSAIDS) and gastroprotective NSAIDS on the gastrointestinal tract: a narrative review","volume":"15","author":"Sohail","year":"2023","journal-title":"Cureus"},{"key":"10.1016\/j.jep.2025.120728_bib94","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxicon.2017.01.004","article-title":"Bufadienolides from amphibians: a promising source of anticancer prototypes for radical innovation, apoptosis triggering and Na+\/K+-ATPase inhibition","volume":"127","author":"Sousa","year":"2017","journal-title":"Toxicon"},{"key":"10.1016\/j.jep.2025.120728_bib95","first-page":"247","article-title":"Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis","volume":"150","author":"Souza-Filho","year":"1997","journal-title":"J. Pathol."},{"key":"10.1016\/j.jep.2025.120728_bib96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2018.12.032","article-title":"In vitro and In vivo anti-helicobacter pylori activity of Casearia sylvestris leaf derivatives","volume":"233","author":"Sp\u00f3sito","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2025.120728_bib97","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jaci.2019.01.031","article-title":"Mast cells within cellular networks","volume":"144","author":"Stassen","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.jep.2025.120728_bib98","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1590\/1983-084X\/09_116","article-title":"Ethnobotany survey of medicinal trees of the Jos\u00e9 Milanese Municipal Ecological Park, city of Crici\u00fama, state of Santa Catarina \u2013 brazil","volume":"16","author":"Tomazi","year":"2014","journal-title":"Rev. Bras. Plantas Med."},{"key":"10.1016\/j.jep.2025.120728_bib99","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/hlca.200900211","article-title":"Neolignans from the leaves of Casearia sylvestris Swartz","volume":"93","author":"Wang","year":"2010","journal-title":"Helv. Chim. Acta"},{"key":"10.1016\/j.jep.2025.120728_bib100","article-title":"Advancing herbal medicine: enhancing product quality and safety through robust quality control practices","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Pharmacol."},{"year":"1995","series-title":"Experimental and Surgical Techniques in the Rat","author":"Waynforth","key":"10.1016\/j.jep.2025.120728_bib101"},{"key":"10.1016\/j.jep.2025.120728_bib102","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenan-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.jep.2025.120728_bib103","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbspin.2023.105685","article-title":"NSAID: current limits to prescription","volume":"91","author":"Wirth","year":"2024","journal-title":"Jt. Bone Spine"},{"key":"10.1016\/j.jep.2025.120728_bib104","doi-asserted-by":"crossref","DOI":"10.1016\/j.crphar.2024.100192","article-title":"The relationship between gender and pharmacology","volume":"7","author":"Younes","year":"2024","journal-title":"Curr. Res. Pharmacol. Drug Discov."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125014205?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874125014205?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T03:35:41Z","timestamp":1764041741000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874125014205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":102,"alternative-id":["S0378874125014205"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2025.120728","relation":{},"ISSN":["0378-8741"],"issn-type":[{"type":"print","value":"0378-8741"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"An antitumoral fraction with casearin-like diterpenes exhibits potent acute anti-inflammatory effectiveness and systemic subchronic toxicity","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2025.120728","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"120728"}}