Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role
Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role
复制标题
没食子酸对乙醇诱导的大鼠胃溃疡的胃保护作用：Nrf2/HO-1信号传导和抗凋亡作用的参与
DOI：
10.1016/j.biopha.2020.110075
复制
发表时间：
2020-06-01
影响因子：
7.5
通讯作者：
Wang, Si-Wang
中科院分区：
文献类型：
--
作者：
Zhou, Dan;Yang, Qian;Wang, Si-Wang
没食子酸（3，4，5-trihydroxybenzoic acid，GA）是一种酚类化合物，存在于我国传统药用植物或中成药中，如飞扬肠胃炎胶囊（FY capsule），几十年来一直用于治疗胃肠道疾病。然而，GA的胃保护作用的证据是缺乏的，药理学机制仍然有限。本研究旨在探讨甘草酸对大鼠乙醇性胃溃疡的保护作用及其机制。用无水乙醇（5 mL/kg，i.g.）雄性Sprague-Dawley大鼠经口给予GA（10、30和50 mg/kg）、FY胶囊（0.4 g/kg）和30 mg/kg兰索拉唑。生理盐水和兰索拉唑分别用作阴性和阳性对照。用乙醇诱导大鼠导致溃疡指数、炎性细胞因子标志物（IL-1 β、IL-6和TNF-α）、TBARS、Bax和Caspase-3蛋白表达的血清水平显著升高，内源性抗氧化剂（SOD、CAT和GSH）、胃粘膜保护因子（PGE 2和NO）和Bcl-2蛋白表达的活性或水平显著降低。与乙醇组相比，GA预处理组溃疡指数、炎症细胞因子、TBARS、Bax和Caspase-3蛋白表达显著降低，内源性抗氧化剂活性、PGE 2和NO水平、Bcl-2、Nrf 2和HO-1蛋白表达显著升高。本实验研究了没食子酸和FY胶囊对大鼠乙醇性胃溃疡的保护作用。GA和FY胶囊抗乙醇性胃溃疡的机制可能与Nrf 2/HO-1抗氧化通路有关，并通过调节Bax、Bcl-2和Caspase-3发挥抗凋亡作用。
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1 beta, IL-6 and TNF-alpha), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.