Natural and Synthetic Bioactive Products Postgraduate Program, Health Sciences Center, Federal University of Paraiba, Paraíba, João Pessoa, PB, Brazil.
Department of Biophysics and Pharmacology and Department of Morphology, Histology and Basic Pathology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2265-2278. doi: 10.1007/s00210-020-01894-2. Epub 2020 Jul 8.
Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000 mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD set around 2500 mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200 mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1β) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms. Graphical abstract.
迷迭香酸（RA）是存在于几种植物物种中的一种次生代谢物，已在实验中表现出抗氧化、抗过敏、抗癌、抗菌、神经保护和保肝作用。由于先前发现的有前景的药理学特性，本研究旨在使用动物模型评估 RA 的口服急性毒性和胃保护作用。急性毒性根据 OECD 指南 423 进行评估。使用乙醇、应激、非甾体抗炎药和幽门结扎诱导的胃溃疡模型来研究抗溃疡特性。还从乙醇诱导的胃损伤方案评估了相关的作用机制。RA（300 和 2000mg/kg）在行为、水和食物摄入、体重和器官重量参数方面没有变化，LD 约为 2500mg/kg。RA 在所有评估剂量（25、50、100 和 200mg/kg）下均表现出胃保护活性，使用了不同的动物模型。此外，观察到这种作用与胃酸参数（pH、体积和[H]）的调节、一氧化氮、粘液和前列腺素的参与无关。然而，对于 RA 处理组，发现增加了巯基基团、GSH 和 IL-10 水平，同时降低了促炎细胞因子（TNF-α和 IL-1β）水平。RA 具有低急性毒性和胃保护活性，通过细胞保护、抗氧化和抗炎机制预防溃疡形成。
