Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil.
Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa, PB, Brazil.
Phytomedicine. 2021 Jun;86:153497. doi: 10.1016/j.phymed.2021.153497. Epub 2021 Feb 16.
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.
To evaluate their gastroduodenal antiulcer activity, gastric healing and toxicity in experimental models.
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.
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 and water intake.
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.
对伞花烃和迷迭香酸是几种药用植物和香料中发现的次生代谢物。先前的研究表明它们具有抗炎、抗氧化和细胞保护作用。
评估它们在实验模型中的胃十二指肠抗溃疡活性、胃愈合和毒性。
通过口服预处理评估盐酸/乙醇诱导的胃损伤和半胱胺诱导的十二指肠损伤模型的预防抗溃疡作用。使用醋酸诱导的大鼠胃溃疡模型和口服治疗 14 天，进行胃愈合、潜在机制和重复剂量毒性。
在盐酸/乙醇诱导的胃溃疡和半胱胺诱导的十二指肠损伤中，对伞花烃和迷迭香酸（50-200mg/kg）显著减少溃疡面积，从而防止损伤形成。在醋酸诱导的溃疡模型中，两种化合物（200mg/kg）均显著减轻溃疡性损伤。这些作用与还原型谷胱甘肽（GSH）和白细胞介素（IL）-10水平的增加有关，与丙二醛（MDA）、IL-1β、肿瘤坏死因子（TNF）-α、总和线粒体活性氧（ROS）水平的降低有关。还证明了核因子 kappa B（NFκB）的下调和细胞因子信号转导抑制物（SOCS）3 的表达增强。此外，在治疗组中增加了阳性血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）-2 和环氧化酶（COX）-2 染色细胞。治疗还上调了胃组织中的血小板衍生生长因子（PDGF）、碱性成纤维细胞生长因子（bFGF）、转化生长因子（TGF）-β 和表皮生长因子受体（EGFR）。在分离的胃上皮细胞中，这种愈合作用似乎与细胞凋亡、增殖、存活和蛋白磷酸化的调节有关，如细胞外信号调节激酶（ERK）1/2 和丝裂原活化蛋白激酶（MAPK）p38。口服治疗 14 天未改变心脏、肝脏、脾脏和肾脏的重量，也未改变生化和血液学评估参数。对伞花烃和迷迭香酸也能保护动物免受体重减轻，维持饲料和水的摄入。
数据表明，对伞花烃和迷迭香酸具有低毒性、抗溃疡和胃愈合活性。抗氧化和免疫调节特性似乎与治疗效果以及与组织修复相关的不同因素的诱导有关。
