{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:57:36Z","timestamp":1788393456890,"version":"build-2803163510"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    (-)-Carveol (\n                    <jats:italic>p<\/jats:italic>\n                    -Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as\n                    <jats:italic>Cymbopogon giganteus<\/jats:italic>\n                    ,\n                    <jats:italic>Illicium pachyphyllum<\/jats:italic>\n                    and in spices such as\n                    <jats:italic>Carum carvi<\/jats:italic>\n                    (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Hypothesis\/Purpose:<\/jats:bold>\n                    The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, NSAIDs and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    (-)-Carveol has low toxicity, with a lethal dose 50% (LD\n                    <jats:sub>50<\/jats:sub>\n                    ) equal to or greater than 2,500\u00a0mg\/kg according to OECD guide n\u00ba 423. In all gastric ulcer induction methods evaluated, (-)-Carveol (25, 50, 100 and 200\u00a0mg\/kg, p.o.) significantly reduced the ulcerative lesion in comparison with the respective control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotective, antioxidant and immunoregulatory effects were evaluated. In the experimental protocol of pylorus ligation-induced gastric ulcer, (-)-Carveol (100\u00a0mg\/kg) reduced (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) the volume of gastric secretion in both routes (oral and intraduodenal). The previous administration of blockers NEM (sulfhydryl groups blocker), L-NAME (nitric oxide synthesis inhibitor), glibenclamide (K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel blocker) and indomethacin (cyclo-oxygenase inhibitor), significantly reduced the gastroprotection exercised by (-)-Carveol, suggesting the participation of these pathways in its gastroprotective activity. In addition, treatment with (-)-Carveol (100\u00a0mg\/kg) increased (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) mucus adhered to the gastric wall. Treatment also increased (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) levels of reduced glutathione (GSH), superoxide dismutase (SOD) and interleukin-10 (IL-10). It also reduced (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1\u03b2) and tumor necrosis factor-alpha (TNF-\u03b1) levels.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Thus, it is possible to infer that (-)-Carveol presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.736829","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T05:45:39Z","timestamp":1629697539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["(-)-Carveol Prevents Gastric Ulcers via Cytoprotective, Antioxidant, Antisecretory and Immunoregulatory Mechanisms in Animal Models"],"prefix":"10.3389","volume":"12","author":[{"given":"Catarina Alves de Lima","family":"Serafim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elaine Cristina","family":"Araruna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edvaldo Balbino","family":"Alves J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiliane Macena Oliveira","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessa Oliveira","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Sobral","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano Francisco","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurigena Antunes","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00f4nia Maria","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0216737","DOI":"10.1371\/journal.pone.0216737","article-title":"Prodigiosins from a marine sponge-associated actinomycete attenuate HCl\/ethanol-induced gastric lesion via antioxidant and anti-inflammatory mechanisms","volume":"14","author":"Abdelfattah","year":"2019","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.yrtph.2016.07.011","article-title":"The acute lethal dose 50 (LD50) of caffeine in albino rats","volume":"80","author":"Adamson","year":"2016","journal-title":"Regul. 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