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Abstract Title:

Effect of p-cymene and rosmarinic acid on gastric ulcer healing - Involvement of multiple endogenous curative mechanisms.

Abstract Source:

Phytomedicine. 2021 Feb 16:153497. Epub 2021 Feb 16. PMID: 33745762

Abstract Author(s):

Rodrigo de Oliveira Formiga, Edvaldo Balbino Alves Júnior, Roseane Carvalho Vasconcelos, Aurigena Antunes Araújo, Thaís Gomes de Carvalho, Raimundo Fernandes de Araújo Junior, Gerlane Bernardo Coelho Guerra, Giciane Carvalho Vieira, Kardilandia Mendes de Oliveira, Margareth de Fátima Formiga Melo Diniz, Marianna Vieira Sobral, José Maria Barbosa Filho, Fernando Spiller, Leônia Maria Batista

Article Affiliation:

Rodrigo de Oliveira Formiga

Abstract:

BACKGROUND: p-Cymene and rosmarinic acid are secondary metabolites found in several medicinal plants and spices. Previous studies have demonstrated their anti-inflammatory, antioxidant, and cytoprotective effects.

PURPOSE: To evaluate their gastroduodenal antiulcer activity, gastric healing and toxicity in experimental models.

METHODS: Preventive antiulcer effects were assessed using oral pre-treatment on HCl/ethanol-induced gastric lesions and cysteamine-induced duodenal lesions models. Gastric healing, the underlining mechanisms and toxicity after repeated doses were carried out using the acetic acid-induced gastric ulcer rat model and oral treatment for 14 days.

RESULTS: In the HCl/ethanol-induced gastric ulcer and cysteamine-induced duodenal injury, p-cymene and rosmarinic acid (50-200 mg/kg) decreased significantly the ulcer area, and so prevented lesions formation. In the acetic acid-induced ulcer model, both compounds (200 mg/kg) markedly reduced the ulcerative injury. These effects were related to an increase in the levels of reduced glutathione (GSH) and interleukin (IL)-10, and due to a decrease in malondialdehyde (MDA), IL-1β, tumor necrosis factor (TNF)-α, total and mitochondrial reactive oxygen species (ROS) levels. Downregulation of factor nuclear kappa B (NFκB) and enhanced expression of suppressor of cytokine signaling (SOCS)3 were also demonstrated. Furthermore, positive vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-2, and cyclooxygenase (COX-2)-stained cells were increased in treated groups. Treatment also upregulated the platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-β and epidermal growth factor receptor (EGFR) in gastric tissues. In isolated gastric epithelial cells this healing effect seems to be linked to a modulation of apoptosis, proliferation, survival and protein phosphorylation, such as the extracellular signal-regulated kinases (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK). Oral toxicity investigation for 14 days revealed no alterations in heart, liver, spleen, and kidneys weight nor the biochemical and hematological assessed parameters. p-Cymene and rosmarinic acid also protected animals from body weight loss maintaining feed andwater intake.

CONCLUSIONS: Data altogether suggest low toxicity, antiulcer and gastric healing activities of p-cymene and rosmarinic acid. Antioxidant and immunomodulatory properties seem to be involved in the curative effect as well as the induction of different factors linked to tissue repair.

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