{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:44:10Z","timestamp":1777909450970,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medicinal Food"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>\n                    Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) alters osteoclast function. Ursolic acid (UA) can inhibit the expression of interleukin-17 (IL-17). Evaluate the influence of UA treatment on the severity of BRONJ in zoledronic acid (ZA)-treated rats\u2019 jaws. Fifty male Wistar rats were used, divided into a negative control group (0.1 mL\/kg sterile saline), a positive control group (ZA, 0.20 mg\/kg), and three test groups treated with ZA and UA 10, 20 or 40 mg\/kg by gavage every three days from the beginning of the protocol until euthanasia. After three consecutive weekly administrations of ZA intravenous (i.v.), exodontia of the 1st left lower molar was performed, administration of an additional dose of ZA, and euthanasia after 28 days from exodontia. Hemimandibles were removed for radiographical, histological, and immunohistochemical analysis and gum samples for Western blotting. The femur was removed for the three-point bending test. Analysis of variance (ANOVA)\/Bonferroni was used. Radiographically, UA reduced the area suggestive of OM (7.2\u2009 \u00b1\u2009 0.6 vs. 5.2 \u00b1\u2009 0.4,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = .015) and the highest dose of UA reversed the number of nonviable osteocytes (80.3 \u2009\u00b1 \u20094.9 vs. 55.4\u2009\u00b1\u2009 4.6,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = .007), suggesting bone healing through IL-17 inhibition. UA reduced the number of polymorphonuclear cells (208 \u00b1 17 vs. 30 \u00b1 9,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001), mononuclear cells (207 \u00b1 34 vs. 74 \u00b1 20,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.001) and apoptotic osteoclasts (87 \u00b1 4 vs. 61 \u00b1 3,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001), observing that these parameters are higher in groups treated only with ZA. The two highest doses of UA reduced the immunoexpression of IL-17 (429 \u00b1 45 vs. 300 \u00b1 42,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = .014) and increased the percentage of circulating lymphocytes (69 \u00b1 2 vs. 82 \u00b1 2,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001). AZ increased the expression of RORyT and the highest dose of UA (1.887 \u2009\u00b1 \u20090.114 vs. 0.869 \u2009\u00b1 \u20090.050,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; .001),) reduced this expression, suggesting that UA may be a specific antagonist of RORyT, which has the capacity to inhibit the expression of this protein. UA promise in reducing the severity of ZA-induced ONJ.\n                  <\/jats:p>","DOI":"10.1089\/jmf.2023.0167","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T11:15:55Z","timestamp":1750072555000},"page":"860-868","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ursolic Acid Attenuates Inflammatory and Severity of Osteonecrosis in Rats Treated with Zoledronic Acid"],"prefix":"10.1177","volume":"28","author":[{"given":"L\u00edvia Moreira Caetano","family":"Coelho","sequence":"first","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."},{"name":"Division of Oral Pathology, Department of Clinical Dentistry, School of Pharmacy, Dentistry and Nursing, Universidade Federal do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa Mour\u00e3o","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Vitor","family":"Mota Lemos","sequence":"additional","affiliation":[{"name":"Division of Oral Pathology, Dentistry Department of Clinical Dentistry, School of Pharmacy, Dentistry and Nursing, Universidade Federal do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udia do \u00d3.","family":"Pessoa","sequence":"additional","affiliation":[{"name":"PostDoc Pharmacology, Department head of Physiology and Pharmacology at the Federal University of Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J\u00falia Barbosa","family":"Bezerra","sequence":"additional","affiliation":[{"name":"PostDoc Pharmacology, Department and laboratory of molecular biology and genetics of the Instituto do C\u00e2ncer do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia Vila Real","family":"Lima","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elisa Quezado","family":"Lima Verde","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."},{"name":"Division of Oral Pathology, Department of Clinical Dentistry, School of Pharmacy, Dentistry and Nursing, Universidade Federal do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1513-9027","authenticated-orcid":false,"given":"Paulo Goberl\u00e2nio de","family":"Barros Silva","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."},{"name":"Division of Oral Pathology, Department of Clinical Dentistry, School of Pharmacy, Dentistry and Nursing, Universidade Federal do Cear\u00e1, Fortaleza, Brazil."},{"name":"Department and laboratory of molecular biology and genetics of the Instituto do C\u00e2ncer do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabr\u00edcio Bitu","family":"Sousa","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."},{"name":"Division of Oral Pathology, Department of Clinical Dentistry, School of Pharmacy, Dentistry and Nursing, Universidade Federal do Cear\u00e1, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thinali Sousa","family":"Dantas","sequence":"additional","affiliation":[{"name":"Dentistry Department of Dentistry, Laboratory of Oral Pathology, Unichristus, Fortaleza, Brazil."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43798-z"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2013.11.005"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2014.04.031"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12513"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2012.42.5.158"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.21609"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.07.011"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2016.10.002"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-695X2005000400015"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.58"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.05.028"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0615"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.11.033"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104680"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2017.1388167"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7794"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1780-z"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.02.018"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.18039"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2015.05.015"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199754060-00003"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2015.04.020"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-018-3050-y"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4012-5"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.03.001"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C111.250407"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.2821"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2014.03.011"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608501006"}],"container-title":["Journal 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