{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:29Z","timestamp":1785416489361,"version":"3.56.0"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq) from Brazil","award":["316996\/2023-8"],"award-info":[{"award-number":["316996\/2023-8"]}]},{"award":["316996\/2023-8"],"award-info":[{"award-number":["316996\/2023-8"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior Brazil","award":["001"],"award-info":[{"award-number":["001"]}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Para\u00edba State Research Foundation (FAPESQ-PB) through PRONEX program","award":["030\/2023"],"award-info":[{"award-number":["030\/2023"]}]},{"name":"CNPQ\/FAPESQ-PB through: Regional Scientific and Technological Development Program","award":["300989\/2022-9"],"award-info":[{"award-number":["300989\/2022-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Cenostigma pluviosum var. peltophoroides, known as \u201csibipiruna,\u201d is a plant rich in polyphenols used in traditional medicine for gastrointestinal disorders. The study aimed to investigate the chemical composition of the crude ethanolic extract of the stem bark (CEECP), evaluating its in vivo toxicity, genotoxicity, mutagenicity and anti-inflammatory activity. The plant material was macerated in 95% ethanol for 72 h, and the solvent was removed by rotary evaporation to obtain CEECP. Chemical characterization was performed by HPLC-ESI-MS\/MS in negative mode. In vivo approaches were performed using male\/female Swiss albino mice. Acute toxicity was assessed at a single high dose of 2000 mg\/kg. Mutagenicity was investigated by the micronucleus test and genotoxicity by the comet assay, both at a dose of 2000 mg\/kg. Anti-inflammatory activity was evaluated in carrageenan-induced paw edema and peritonitis models, at doses of 50, 100, and 200 mg\/kg. HPLC-ESI-MS\/MS analysis showed the presence of hydrolyzable tannins, phenolic acid heterosides, and biflavonoids. The safety profile of the CEECP was demonstrated for the first time, with no evidence of acute toxicity, mortality, mutagenicity, or genotoxicity at the tested doses. The extract significantly reduced paw edema in a dose-dependent manner at doses of 100 and 200 mg\/kg, with inhibition rates of 65.78% and 73.12%, respectively, and also decreased leukocyte migration in the peritonitis model by 61.81% and 72.79% at the same doses. These findings indicate the CEECP as a source of pharmacologically relevant phytocompounds and, most notably, demonstrate its pronounced anti-inflammatory activity. Furthermore, the extract exhibited a favorable safety profile in the toxicological evaluations, highlighting the extract as a promising anti-inflammatory agent.<\/jats:p>","DOI":"10.3390\/plants15101508","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:50:12Z","timestamp":1778835012000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytochemical Profile and In Vivo Assessment of Toxicity and Anti-Inflammatory Activity of Cenostigma pluviosum var. peltophoroides (Benth.) Gagnon &amp; G.P. Lewis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3062-7707","authenticated-orcid":false,"given":"Natanael Teles Ramos de","family":"Lima","sequence":"first","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Ribeiro de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, State University of Para\u00edba, Campina Grande 58429-500, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Gomes da","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-0449","authenticated-orcid":false,"given":"Geovana Ferreira Guedes","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-1075","authenticated-orcid":false,"given":"Alan Ferreira","family":"Alves","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana Maria","family":"Fechine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, State University of Para\u00edba, Campina Grande 58429-500, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-0975","authenticated-orcid":false,"given":"Maria de Fatima","family":"Agra","sequence":"additional","affiliation":[{"name":"Program of Biotechnology, Center for Biotechnology, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-150X","authenticated-orcid":false,"given":"Alisson Mac\u00e1rio de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-2605","authenticated-orcid":false,"given":"Josean Fechine","family":"Tavares","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Sobral da","family":"Silva","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-4096","authenticated-orcid":false,"given":"Jos\u00e9 Maria Barbosa","family":"Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Yoldi, M.J. (2021). Anti-Inflammatory and antioxidant properties of plant extracts. Antioxidants, 10.","DOI":"10.3390\/antiox10060921"},{"key":"ref_2","first-page":"4","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":"ref_3","doi-asserted-by":"crossref","first-page":"114436","DOI":"10.1016\/j.jep.2021.114436","article-title":"A review of the traditional use of southern African medicinal plants for the treatment of inflammation and inflammatory pain","volume":"283","author":"Khumalo","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","first-page":"5794350","article-title":"Natural products for cancer therapy: A review of their mechanism of actions and toxicity in the past decade","volume":"2022","author":"Abdalla","year":"2022","journal-title":"J. Trop. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Emerald, M. (2024). Medicinal plants: Therapeutic potential, safety, and toxicity. Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, Springer International Publishing.","DOI":"10.1007\/978-3-030-73317-9_90-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100129","DOI":"10.1016\/j.ccmp.2024.100129","article-title":"A comprehensive review on pre-clinical safety and toxicity of medicinal plants","volume":"4","author":"Mugale","year":"2024","journal-title":"Clin. Complement. Med. Pharmacol."},{"key":"ref_7","first-page":"1","article-title":"Chemical composition, biological activities and traditional uses of plants from the segregated genus Caesalpinia sensu lato","volume":"23","author":"David","year":"2024","journal-title":"Phytochem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7887","DOI":"10.3390\/molecules17077887","article-title":"The genus Caesalpinia L. (Caesalpiniaceae): Phytochemical and pharmacological characteristics","volume":"17","author":"Zanin","year":"2012","journal-title":"Molecules"},{"key":"ref_9","unstructured":"Carvalho, P.E.R. (2008). Sibipiruna: Caesalpinia pluviosa var. peltophoroides. Esp\u00e9cies Arb\u00f3reas Brasilei-Ras. Embrapa Informa\u00e7\u00e3o Tecnol\u00f3gica, Embrapa Florestas."},{"key":"ref_10","unstructured":"Gaem, P.H. (2026, February 13). Cenostigma in Flora e Funga do Brasil. Jardim Bot\u00e2nico do Rio de Janeiro, Available online: https:\/\/floradobrasil.jbrj.gov.br\/FB606077."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0378-8741(99)00158-0","article-title":"Medicinal plants uses of the Tacana, an Amazonian Bolivian ethnic group","volume":"70","author":"Bourdy","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1475-2875-10-112","article-title":"In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa","volume":"10","author":"Kayano","year":"2011","journal-title":"Malar. J."},{"key":"ref_13","first-page":"1318","article-title":"Leaves from the Tree Poincianella pluviosa as a Renewable Source of Antiplasmodial Compounds against Chloroquine-Resistant Plasmodium falciparum","volume":"29","author":"Nascimento","year":"2017","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.injury.2020.02.027","article-title":"Stem bark extract of Poincianella pluviosa incorporated in polymer film: Evaluation of wound healing and anti-staphylococcal activities","volume":"51","author":"Guidi","year":"2020","journal-title":"Injury"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Andriani, G.M., Morguette, A.E.B., Spoladori, L.F.A., Pereira, P.M.L., Cabral, W.R.C., Fernandes, B.T., Tavares, E.R., Almeida, R.S., Lancheros, C.A.C., and Nakamura, C.V. (2021). Antifungal Combination of Ethyl Acetate Extract of Poincianella pluviosa (DC.) L. P. Queiros Stem Bark With Amphotericin B in Cryptococcus neoformans. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.660645"},{"key":"ref_16","first-page":"7297","article-title":"Antiviral activity of Cenostigma pluviosum var. pel-tophoroides extract and fractions against SARS-CoV-2","volume":"41","author":"Moraes","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/chromsci\/bms138","article-title":"Chemical Profiling of the Chinese Herb Formula Xiao-Cheng-Qi Decoction Using Liquid Chromatography Coupled with Electrospray Ionization Mass Spectrometry","volume":"51","author":"Zhao","year":"2012","journal-title":"J. Chromatogr. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14821","DOI":"10.3390\/molecules171214821","article-title":"Rapid and Comprehensive Evaluation of (Poly)phenolic Compounds in Pomegranate (Punica granatum L.) Juice by UHPLC-MSn","volume":"17","author":"Mena","year":"2012","journal-title":"Molecules"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1016\/j.chroma.2009.05.038","article-title":"High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a lemon verbena extract","volume":"1216","author":"Funes","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Navarro, M., Arnaez, E., Moreira, I., Quesada, S., Azofeifa, G., Wilhelm, K., Vargas, F., and Chen, P. (2019). Polyphenolic Characterization, Antioxidant, and Cytotoxic Activities of Mangifera indica Cultivars from Costa Rica. Foods, 8.","DOI":"10.3390\/foods8090384"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1021\/jf506277p","article-title":"Phenolic Constituents in Commercial Aqueous Quillaja (Quillaja saponaria Molina) Wood Extracts","volume":"63","author":"Maier","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","first-page":"1691","article-title":"Phenolic Constituents of Erigeron floribundus (Asteraceae), a Cameroonian Medicinal Plant","volume":"9","author":"Berto","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1002\/jssc.201800480","article-title":"Liquid chromatography coupled with time-of-flight tandem mass spectrometry for comprehensive phenolic characterization of pomegranate fruit and flower extracts used as ingredients in botanical dietary supplements","volume":"41","author":"Liu","year":"2018","journal-title":"J. Sep. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fitote.2014.10.007","article-title":"Hydrolyzable tannins from hydroalcoholic extract from Poincianella pluviosa stem bark and its wound-healing properties: Phytochemical investigations and influence on in vitro cell physiology of human keratinocytes and dermal fibroblasts","volume":"99","author":"Bueno","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lachowicz-Wi\u015bniewska, S., Pratap-Singh, A., Kapusta, I., Kruszy\u0144ska, A., Rapak, A., Ochmian, I., Cebulak, T., \u017bukiewicz-Sobczak, W., and Rubi\u0144ski, P. (2022). Flowers and Leaves Extracts of Stachys palustris L. Exhibit Stronger Anti-Proliferative, Antioxidant, Anti-Diabetic, and Anti-Obesity Potencies than Stems and Roots Due to More Phenolic Compounds as Revealed by UPLC-PDA-ESI-TQD-MS\/MS. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070785"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Samet, S., Ayachi, A., Fourati, M., Mallouli, L., Allouche, N., Treilhou, M., T\u00e9n\u00e9, N., and Mezghani-Jarraya, R. (2022). Antioxidant and Antimicrobial Activities of Erodium arborescens Aerial Part Extracts and Characterization by LC-HESI-MS2 of Its Acetone Extract. Molecules, 27.","DOI":"10.3390\/molecules27144399"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Santiago, J.C.C., Albuquerque, C.A.B., Muribeca, A.d.J.B., S\u00e1, P.R.C., Pamplona, S.d.G.S.R., Silva, C.Y.Y.e., Ribera, P.C., Fontes-J\u00fanior, E.d.A., and da Silva, M.N. (2022). Margaritaria nobilis L.F. (Phyllanthaceae): Ethnopharmacology and Application of Computational Tools in the Annotation of Bioactive Molecules. Metabolites, 12.","DOI":"10.3390\/metabo12080681"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129959","DOI":"10.1016\/j.foodchem.2021.129959","article-title":"Advanced characterization of polyphenols from Myrciaria jaboticaba peel and lipid protection in in vitro gastrointestinal digestion","volume":"359","author":"Tarone","year":"2021","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/pca.2691","article-title":"Characterisation of Pomegranate-Husk polyphenols and Semi-Preparative fractionation of punicalagin","volume":"28","author":"Michel","year":"2017","journal-title":"Phytochem. Anal."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shahzad, M.N., Ahmad, S., Tousif, M.I., Ahmad, I., Rao, H., Ahmad, B., and Basit, A. (2022). Profiling of phytochemicals from aerial parts of Terminalia neotaliala using LC-ESI-MS2 and determination of antioxidant and enzyme inhibition activities. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266094"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.bjp.2017.07.001","article-title":"Identification of phenolic compounds in Myricaria bracteata leaves by high-performance liquid chromatography with a diode array detector and liquid chromatography with tandem mass spectrometry","volume":"27","author":"Chernonosov","year":"2017","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_32","first-page":"830","article-title":"Integrative Analysis Based on HPLC-DAD-MS\/MS and NMR of Bertholletia excelsa Bark Biomass Residues: Determination of Ellagic Acid Derivatives","volume":"30","author":"Hanna","year":"2018","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_33","first-page":"1475","article-title":"Chemical Prospection of Qualea grandiflora Mart. Fruit and Stem Extracts and Their in vitro and in vivo Antiplasmodial Activity","volume":"31","author":"Neto","year":"2020","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_34","first-page":"239","article-title":"Profiling of gallic and ellagic acid derivatives in different plant parts of Terminalia arjuna by HPLC-ESI-QTOF-MS\/MS","volume":"11","author":"Singh","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"C369","DOI":"10.1111\/1750-3841.13220","article-title":"Fresh from the Ornamental Garden: Hips of Selected Rose Cultivars Rich in Phytonutrients","volume":"81","author":"Cunja","year":"2016","journal-title":"J. Food Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10618","DOI":"10.1021\/acs.analchem.3c00957","article-title":"Alternative identification of glycosides using MS\/MS matching with an in silico-modified aglycone mass spectra library","volume":"95","author":"Li","year":"2023","journal-title":"Anal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yu, J., Zhao, X., He, Y., Zhang, Y., and Tang, C. (2025). An Innovative Strategy for Untargeted Mass Spectrometry Data Analysis: Rapid Chemical Profiling of the Medicinal Plant Terminalia chebula Using Ultra-High-Performance Liquid Chromatography Coupled with Q\/TOF Mass Spectrometry\u2013Key Ion Diagnostics\u2013Neutral Loss Filtering. Molecules, 30.","DOI":"10.3390\/molecules30112451"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/10408699891274273","article-title":"Tannins and Human Health: A review","volume":"38","author":"Chung","year":"1998","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_39","unstructured":"Bule, M., Khan, F., Nisar, M.F., Niaz, K., Nabavi, S., Saeedi, M., and Sanches Silva, A. (2020). Tannins (hydrolysable tannins, condensed tannins, phlorotannins, flavono-ellagitannins). Recent Advances in Natural Products Analysis, Elsevier."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"De Almeida Silva Brilhante, A.R.R., De Sousa, G.R., De Aquino-Vital, A.K.S., De Li-ma, N.T.R., De Lima Souza, R.B., De Souza, T.A., Scotti, M.T., Filho, J.M.B., Tavares, J.F., and Da Silva, M.S. (2025). Fabaceae Flavonoids Beyond the Commonplace: A Review of Chemical Diversity, Pharmacological Activities, Mass Spectrometric Profiling and In Silico Insights into Their Subclasses. Plants, 14.","DOI":"10.3390\/plants14233549"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1039\/C5NP00073D","article-title":"Fragmentation reac-tions using electrospray ionization mass spectrometry: An important tool for the struc-tural elucidation and characterization of synthetic and natural products","volume":"33","author":"Demarque","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_42","first-page":"125","article-title":"Signals of diagnostic ions in the product ion spectra of [M \u2212 H]\u2212 ions of methoxylated flavonoids","volume":"33","author":"Gierczyk","year":"2018","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yao, H., Chen, B., Zhang, Y., Ou, H., Li, Y., Li, S., Peiying, S., and Lin, X. (2017). Analysis of the total biflavonoids extract from Selaginella doederleinii by HPLC-QTOF-MS and its in vitro and in vivo anticancer effects. Molecules, 22.","DOI":"10.3390\/molecules22020325"},{"key":"ref_44","unstructured":"Organisation for Economic Co-operation and Development (2001). OECD Guideline for the Testing of Chemicals No. 425: Acute Oral Toxicity\u2014Up-and-Down Procedure, OECD Publishing."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6459","DOI":"10.2147\/DDDT.S494417","article-title":"Traditional Uses, Phytochemistry, Pharmacology and Toxicology of Ruta graveolens L.: A Critical Review and Future Perspectives","volume":"18","author":"Luo","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic. Clin. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.fct.2012.11.027","article-title":"Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L)","volume":"53","author":"Liju","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_48","first-page":"45","article-title":"The effects of ethanol extracts of Jatropha curcas on some hematological parameters of chloroform intoxicated rats","volume":"10","author":"Nwaka","year":"2015","journal-title":"Am.-Euras. J. Sci. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.toxrep.2024.01.005","article-title":"Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats","volume":"12","author":"Obakiro","year":"2024","journal-title":"Toxicol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107794","DOI":"10.1016\/j.toxicon.2024.107794","article-title":"Poisonings in ruminants by Cenostigma pyramidale (Tul.) Gagnon & GP Lewis (Fabaceae): A mini-review of teratogenic potential and phytochemical evidence","volume":"246","author":"Bezerra","year":"2024","journal-title":"Toxicon"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41256","DOI":"10.1039\/C9RA05985G","article-title":"Evaluation of anti-inflammatory, antinociceptive and biological activities of Cenostigma macrophyllum standardized extracts and determination and quantification of the main metabolites","volume":"9","author":"Moreira","year":"2019","journal-title":"RSC Adv."},{"key":"ref_52","first-page":"265","article-title":"Effects of ethanol extract of Cenostigma macrophyllum Tul. (caneleiro) on reproductive parameters of female rats","volume":"20","author":"Santos","year":"2015","journal-title":"Rev. Cuba. Plantas Med."},{"key":"ref_53","unstructured":"Celik, T.A. (2012). Potential Genotoxic and Cytotoxic Effects of Plant Extracts. A Compendium of Essays on Alternative Therapy, InTech."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s42269-022-00803-2","article-title":"Genotoxicity induced by medicinal plants","volume":"46","author":"Bardoloi","year":"2022","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"239","DOI":"10.70151\/c4maw071","article-title":"Tratamento com fra\u00e7\u00f5es de extratos de Caesalpinia peltophoroides em camundongos: Avalia\u00e7\u00e3o mutag\u00eanica, antimutag\u00eanica e metab\u00f3lica","volume":"21","author":"Muller","year":"2024","journal-title":"Rev. Bras. Plantas Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e37985015","DOI":"10.33448\/rsd-v9i8.5015","article-title":"In vivo study on the toxic, cytotoxic, and genotoxic potentials of stem bark ethanolic extract of Cenostigma gardnerianum Tul. (Caneleiro)","volume":"9","author":"Sampaio","year":"2020","journal-title":"Res. Soc. Dev."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Plaskova, A., and Mlcek, J. (2023). New insights of the application of water or ethanol-water plant extract rich in active compounds in food. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1118761"},{"key":"ref_58","first-page":"3897","article-title":"Fabaceae: A significant flavonoid source for plant and human health","volume":"8","author":"Noviany","year":"2022","journal-title":"Phys. Sci. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Al-Naqeb, G., Kalmpourtzidou, A., Giampieri, F., De Giuseppe, R., and Cena, H. (2024). Genotoxic and antigenotoxic medicinal plant extracts and their main phytochemicals: \u201cA review\u201d. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1448731"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/pca.3031","article-title":"In vivo anti-inflammatory activity of Fabaceae species extracts screened by a new ex vivo assay using human whole blood","volume":"32","author":"Rosa","year":"2021","journal-title":"Phytochem. Anal."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Fraga-Corral, M., Otero, P., Cassani, L., Echave, J., Garcia-Oliveira, P., Carpena, M., Chamorro, F., Louren\u00e7o-Lopes, C., Prieto, M.A., and Simal-Gandara, J. (2021). Traditional applications of tannin rich extracts supported by scientific data: Chemical composition, bioavailability and bioaccessibility. Foods, 10.","DOI":"10.3390\/foods10020251"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.2174\/0929867323666160919111559","article-title":"Ellagitannins, gallotannins and their metabolites-the contribution to the anti-inflammatory effect of food products and medicinal plants","volume":"25","author":"Kiss","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yahfoufi, N., Alsadi, N., Jambi, M., and Matar, C. (2018). The immunomodulatory and Anti-Inflammatory role of polyphenols. Nutrients, 10.","DOI":"10.3390\/nu10111618"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Marrone, G., Di Lauro, M., Izzo, F., Cornali, K., Masci, C., Vita, C., Occhiuto, F., Daniele, N., Lorenzo, A., and Noce, A. (2024). Possible beneficial effects of hydrolyzable tannins deriving from Castanea sativa L. in internal medicine. Nutrients, 16.","DOI":"10.3390\/nu16010045"},{"key":"ref_65","first-page":"243","article-title":"Mouse paw edema. A new model for inflammation?","volume":"20","author":"Henriques","year":"1987","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/sj.bjp.0705650","article-title":"Carra-geenan-induced mouse paw edema is biphasic, age-weight dependent and displays dif-ferential nitric oxide cyclooxygenase-2 expression","volume":"142","author":"Posadas","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"142087","DOI":"10.1155\/2012\/142087","article-title":"Animal models as tools to investigate antidiabetic and Anti-Inflammatory plants","volume":"2012","author":"Eddouks","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11101-018-9589-6","article-title":"Insights on the pharmacological, phytochemical and ethnobotanical aspects of Artemisia roxburghiana: A rather less explored but therapeutically important species of lower Himalayas","volume":"18","author":"Kumar","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12964-020-00621-x","article-title":"Molecular basis of carrageenan-induced cytokines production in macrophages","volume":"18","author":"Lopes","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in inflammation and cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jin, F., Cheng, D., Tao, J.-Y., Zhang, S.-L., Pang, R., Guo, Y.-J., Ye, P., Dong, J.-H., and Zhao, L. (2013). Anti-inflammatory and anti-oxidative effects of corilagin in a rat model of acute cholestasis. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-79"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"114791","DOI":"10.1016\/j.jep.2021.114791","article-title":"Anti-proliferation and anti-inflammation effects of corilagin in rheumatoid arthritis by downregulating NF-\u03baB and MAPK signaling pathways","volume":"284","author":"Shen","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"106823","DOI":"10.1016\/j.intimp.2020.106823","article-title":"Chebulanin exerts its an-tiinflammatory and anti-arthritic effects via inhibiting NF-\u03baB and MAPK activation in collagen-induced arthritis mice","volume":"88","author":"Liu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bbrc.2009.02.022","article-title":"Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-\u03baB and MAPK activation in RAW 264.7 macrophages","volume":"381","author":"Reddy","year":"2009","journal-title":"Biochem. Bio-Phys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yin, J., Kim, H.H., Hwang, I.H., Kim, D.H., and Lee, M.W. (2019). Anti-Inflammatory Effects of Phenolic Compounds Isolated from Quercus mongolica Fisch. ex Ledeb. on UVB-Irradiated Human Skin Cells. Molecules, 24.","DOI":"10.3390\/molecules24173094"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1017\/S0007114510000826","article-title":"NF-\u03baB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts","volume":"104","author":"Larrosa","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2101019","DOI":"10.1002\/mnfr.202101019","article-title":"Urolithins: A Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota","volume":"66","author":"Selma","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_78","first-page":"804","article-title":"Caesalpinioflavone, a New Cytotoxic Biflavonoid Isolated from Caesalpinia pluviosa var. peltophoroides","volume":"26","author":"Zanin","year":"2015","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Domingos, O.S., Alc\u00e2ntara, B.G.V., Santos, M.F.C., Maiolini, T.C.S., Dias, D.F., Baldim, J.L., Lago, J.H.G., Soares, M.G., and Chagas-Paula, D.A. (2019). Anti-Inflammatory Derivatives with Dual Mechanism of Action from the Metabolomic Screening of Poincianella pluviosa. Molecules, 24.","DOI":"10.3390\/molecules24234375"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0378-8741(83)90050-8","article-title":"The pharmacological evaluation of natural products\u2014General and specific approaches to screening ethnopharmaceuticals","volume":"8","author":"Malone","year":"1983","journal-title":"J. Ethnopharmacol."},{"key":"ref_81","first-page":"72","article-title":"Metodologia para avalia\u00e7\u00e3o de plantas com atividade no sistema nervosocentral e alguns dados experimentais","volume":"80","author":"Almeida","year":"1999","journal-title":"Rev. Bras. Farm."},{"key":"ref_82","unstructured":"Organisation for Economic Co-operation and Development (2001). OECD Guideline for the Testing of Chemicals No. 423: Acute Oral Toxicity\u2014Acute Toxic Class Method, OECD Publishing."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0378-4274(96)03847-7","article-title":"The contribution of cytotoxicity to DNA-effects in the single cell gel test (comet assay)","volume":"90","author":"Hartmann","year":"1997","journal-title":"Toxicol. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e03811","DOI":"10.1016\/j.heliyon.2020.e03811","article-title":"Genotoxicity assessment of saline extract from Pilosocereus gounellei (Cactaceae) and its chemopreventive effect against cyclophosphamide-induced DNA damage","volume":"6","author":"Paiva","year":"2020","journal-title":"Heliyon"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"555733","DOI":"10.19080\/OROAJ.2017.08.555733","article-title":"Antinociceptive and Anti-inflammatory Effects of the Hydroalcoholic Fraction from Leaves of Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae) in Rodents","volume":"8","author":"Cavalcanti","year":"2017","journal-title":"Orthop. Rheumatol. Open Access J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1089\/jmf.2020.0013","article-title":"Cenostigma macrophyllum Tul. var. acuminata Teles Freire Fraction Leaves Stimulate Gastric Healing in Rats and Human Cell Cultures","volume":"24","author":"Viana","year":"2020","journal-title":"J. Med. Food"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenin-Induced edema in hind paw of the rat as an assay for antiinflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Exp. Biol. Med."},{"key":"ref_88","unstructured":"Lapa, A.J., Souccar, C., Lima-Landman, T.R., Castro, M.A., and Lima, T.C. (2008). Plantas Medicinais: M\u00e9todos de Avalia\u00e7\u00e3o da Atividade Farmacol\u00f3gica, Sociedade Brasileira de Plantas Medicinais."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1590\/S0102-695X2011005000065","article-title":"Citral reduces nociceptive and inflammatory response in rodents","volume":"21","author":"Moreira","year":"2011","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_90","first-page":"113327","article-title":"Pilosocereus gounellei (Cactaceae) stem extract decreases insulin resistance, inflammation, oxidative stress, and cardio-metabolic risk in diet-induced obese mice","volume":"265","author":"Almeida","year":"2020","journal-title":"J. Ethnopharmacol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/10\/1508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:27:15Z","timestamp":1778837235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/10\/1508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":90,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["plants15101508"],"URL":"https:\/\/doi.org\/10.3390\/plants15101508","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}