{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:42:54Z","timestamp":1767926574265,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"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>The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey\u2013Kramer test. We demonstrated that the repeated administration of compound 48\/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.<\/jats:p>","DOI":"10.3390\/ijms22115983","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T15:58:44Z","timestamp":1622563124000},"page":"5983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of a Cytoprotective Dose of Dehydroleucodine, Xanthatin, and 3-Benzyloxymethyl-5H-furan-2-one on Gastric Mucosal Lesions Induced by Mast Cell Activation"],"prefix":"10.3390","volume":"22","author":[{"given":"Mariano Ezequiel","family":"Vera","sequence":"first","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM-CCT Mendoza-CONICET), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500 Mendoza, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Laura","family":"Mariani","sequence":"additional","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM-CCT Mendoza-CONICET), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500 Mendoza, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM-CCT Mendoza-CONICET), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500 Mendoza, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2407-1765","authenticated-orcid":false,"given":"Alicia Beatriz","family":"Penissi","sequence":"additional","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda \u201cDr. Mario H. Burgos\u201d (IHEM-CCT Mendoza-CONICET), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo, Casilla de Correo 56, 5500 Mendoza, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"662","DOI":"10.2174\/1389557520666191227151939","article-title":"Medicinal Plants in the Treatment of Peptic Ulcer Disease: A Review","volume":"20","author":"Ardalani","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/jgh.12735","article-title":"\u201cGastric cytoprotection\u201d is still relevant","volume":"29","author":"Szabo","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_3","first-page":"5","article-title":"Role of heat shock proteins in gastric inflammation and ulcer healing","volume":"60","author":"Choi","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_4","first-page":"219","article-title":"Peptic Ulcer Disease and Helicobacter pylori infection","volume":"115","author":"Narayanan","year":"2018","journal-title":"Sci. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kuna, L., Jakab, J., Smolic, R., Raguz-Lucic, N., Vcev, A., and Smolic, M. (2019). Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020179"},{"key":"ref_6","first-page":"1","article-title":"Peptic ulcer disease","volume":"367","author":"Dunn","year":"2019","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1159\/000505367","article-title":"Peptic Ulcer: Chapter Closed?","volume":"38","author":"Malfertheiner","year":"2020","journal-title":"Dig. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.coph.2018.08.011","article-title":"Mucosal permeability and mast cells as targets for functional gastrointestinal disorders","volume":"43","author":"Keita","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_9","first-page":"772","article-title":"Mast cells in gastrointestinal disease","volume":"6","author":"Ramsay","year":"2010","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_10","first-page":"1","article-title":"Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings","volume":"23","author":"Hodges","year":"2008","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejphar.2016.02.018","article-title":"Mast cells in gastrointestinal disorders","volume":"778","author":"Bischoff","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000198972","article-title":"Role of mast mediators in pathogenesis of anaphylactic gastric ulcer","volume":"28","author":"Andre","year":"1983","journal-title":"Digestion"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sammarco, G., Gallo, G., Vescio, G., Picciariello, A., De Paola, G., Trompetto, M., Curr\u00f2, G., and Ammendola, M. (2020). Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092852"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cildir, G., Yip, K.H., Pant, H., Tergaonkar, V., Lopez, A.F., and Tumes, D.J. (2021). Understanding mast cell heterogeneity at single cell resolution. Trends Immunol., 1\u201313.","DOI":"10.1016\/j.it.2021.04.004"},{"key":"ref_15","first-page":"139","article-title":"Tryptase staining of mast cells may differentiate eosinophilic esophagitis from gastroesophageal reflux disease","volume":"176","author":"Dellon","year":"2019","journal-title":"Physiol. Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/01913123.2011.606964","article-title":"Intraepithelial infiltration by mast cells in human Helicobacter pylori active gastritis","volume":"35","author":"Caruso","year":"2011","journal-title":"Ultrastruct. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116688","DOI":"10.1016\/j.lfs.2019.116688","article-title":"The important role played by chemokines influence the clinical outcome of Helicobacter pylori infection","volume":"231","author":"Jafarzadeh","year":"2019","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/S0016-5085(97)70167-7","article-title":"Mast cell involvement in gastritis with or without Helicobacter pylori infection","volume":"113","author":"Nakajima","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_19","first-page":"1803","article-title":"Mechanisms of direct gastric mucosal damage by NSAIDs","volume":"65","author":"Kobayashi","year":"2007","journal-title":"Nihon Rinsho"},{"key":"ref_20","first-page":"591","article-title":"Stress and the gut: Pathophysiology, clinical consequences, diagnostic approach and treatment options","volume":"62","author":"Konturek","year":"2011","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1023\/A:1018822215956","article-title":"Gastroduodenal mucosal protection induced by dehydroleucodine: Mucus secretion and role of monoamines","volume":"43","author":"Penissi","year":"1998","journal-title":"Dig. Dis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1023\/A:1026601506677","article-title":"Effect of dehydroleucodine on mucus production: A quantitative study","volume":"44","author":"Penissi","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jep.2005.02.042","article-title":"Anti-ulcerogenic activity of xanthanolide sesquiterpenes from Xanthium cavanillesii in rats","volume":"100","author":"Favier","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ce\u00f1al, J.P., Carreras, C.R., Tonn, C.E., Padr\u00f3n, J.I., Ram\u00edrez, M.A., D\u00edaz, D.D., Garc\u00eda-Tellado, F., and Mart\u00edn, V.S. (2005). Acid-mediated highly regioselective oxidation of substituted furans: A simple and direct entry to substituted butenolides. Synlett, 1575\u20131578.","DOI":"10.1055\/s-2005-869865"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejphar.2009.03.052","article-title":"Novel anti-ulcer \u03b1,\u03b2-unsaturated lactones inhibit compound 48\/80-induced mast cell degranulation","volume":"612","author":"Penissi","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.3109\/10428194.2012.662644","article-title":"Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin","volume":"53","author":"Vera","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00011-020-01380-8","article-title":"Natural \u03b1,\u03b2-unsaturated lactones inhibit neuropeptide-induced mast cell activation in an in vitro model of neurogenic inflammation","volume":"69","author":"Coll","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1440-1746.1998.tb00583.x","article-title":"Gastric mucosal damage induced by compound 48\/80: Roles of serotonin and nitric oxide","volume":"13","author":"Yasuhiro","year":"1998","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_29","first-page":"284","article-title":"Experimental Gastric Ulcer Caused by Histamine in Guinea-Pigs","volume":"292","author":"Turba","year":"1961","journal-title":"Med. Exp."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1267\/ahc.21.25","article-title":"Relationship between the staining property of mast cell granule with alcian blue-safranin O and toluidine blue O, and the content of mast cell protease I in the granule of rat peritoneal mast cell","volume":"21","author":"Koretou","year":"1988","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/JEP.S125383","article-title":"Evaluation of anti-ulcer activity of the leaf extract of Osyris quadripartita Decne. (Santalaceae) in rats","volume":"9","author":"Abebaw","year":"2017","journal-title":"J. Exp. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2174\/1574884714666190312143846","article-title":"A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs","volume":"14","author":"Mishra","year":"2019","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_33","first-page":"1","article-title":"Gastroprotective Activity of the Total Flavones from Abelmoschus manihot (L.) Medic Flowers","volume":"2020","author":"Zhang","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s000110050031","article-title":"Comparison of histamine and serotonin release from rat peritoneal mast cells induced by nerve growth factor and compound 48\/80","volume":"46","author":"Ferjan","year":"1997","journal-title":"Inflamm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000199866","article-title":"Histological evaluation of mast cells in rat gastric mucosal lesions induced by compound 48\/80","volume":"43","author":"Arisawa","year":"1989","journal-title":"Digestion"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1254\/jphs.93.337","article-title":"Protective effect of teprenone against acute gastric mucosal lesions induced by compound 48\/80, a mast cell degranulator, in rats","volume":"93","author":"Ohta","year":"2003","journal-title":"J. Pharmacol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0014-2999(01)00815-9","article-title":"Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48\/80","volume":"414","author":"Kobayashi","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1043-6618(02)00034-8","article-title":"Protective effect of omeprazole against acute gastric mucosal lesions induced by compound 48\/80, a mast cell degranulator, in rats","volume":"46","author":"Kobayashi","year":"2002","journal-title":"Pharmacol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000056135","article-title":"Inhibitory effect of egualen sodium: A new stable derivative of azulene on histamine release from mast cell-like cells in the stomach","volume":"63","author":"Akagi","year":"2001","journal-title":"Pharmacology"},{"key":"ref_40","first-page":"101","article-title":"Saikokeishito extract prevents progression of acute gastric mucosal lesions induced by compound 48\/80, a mast cell degranulator, in rats","volume":"23","author":"Ohta","year":"2006","journal-title":"J. Tradit. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1159\/000085388","article-title":"Plaunotol prevents the progression of acute gastric mucosal lesions induced by compound 48\/80, a mast cell degranulator, in rats","volume":"74","author":"Ohta","year":"2005","journal-title":"Pharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1248\/bpb.29.675","article-title":"Effect of oral vitamin E administration on acute gastric mucosal lesion progression in rats treated with compound 48\/80, a mast cell degranulator","volume":"29","author":"Ohta","year":"2006","journal-title":"Biol. Pharm. Bull."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:09:51Z","timestamp":1760162991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22115983"],"URL":"https:\/\/doi.org\/10.3390\/ijms22115983","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]}}}