Ma Jiale, Huo Huixia, Zhang Hang, Wang Lingxiao, Meng Yingxin, Jin Fengyu, Wang Xinyu, Zhao Yimu, Zhao Yunfang, Tu Pengfei, Song Yuelin, Zheng Jiao, Li Jun
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
Phytomedicine. 2022 Apr;98:153935. doi: 10.1016/j.phymed.2022.153935. Epub 2022 Jan 15.
Injury of gastric epithelial cells is one of the most important pathological features of bile reflux gastritis. Chinese agarwood (the resinous heartwood of Aquilaria sinensis) has been used to treat stomach problems for thousands of years in China. However, the pathological mechanism of epithelial cells death induced by bile acids and the therapeutic target of Chinese agarwood for improving bile reflux gastritis have not yet been fully clarified.
This study aimed to investigate the pro-apoptotic effect of taurocholic acid (TCA) by regulating the ER stress pathway. Moreover, the role of Chinese agarwood 2-(2-phenylethyl)chromone-enriched extract (CPE) to inhibit gastric epithelial cell death induced by TCA was also been demonstrated.
We adopted human gastric epithelial GES-1 cells to explore the mechanism of TCA-induced cell death in vitro. Then the cell viability, apoptosis rate, and protein expressions were evaluated to explore the protective effects of CPE on GES-1 cells by TCA injury. The therapeutic effect of CPE on bile reflux gastritis was further confirmed by the bile reflux mice in vivo.
Our results demonstrated that TCA activated GES-1 cell apoptosis by increased cleavage of caspase-7 and PARP. Further experiments showed that TCA up-regulated endoplasmic reticulum (ER) stress, subsequently triggered the apoptosis of the epithelial cells. Our research explored that CPE is the main effective fraction in Chinese agarwood by preventing the TCA-induced gastric epithelial cell injury. CPE effectively suppressed GES-1 cell apoptosis activated by TCA through inhibiting Perk/eIF2α/CHOP pathway. The anti-apoptotic effect of CPE on gastric mucosa had also been confirmed in vivo. Moreover, the main effective components in CPE corresponding to the protection of epithelial cells were also been identified.
Our finding suggested that CPE recovered the TCA-induced epithelial cell apoptosis by mediating the activation of ER stress, which explored potential medicine to treat bile reflux gastritis.
胃上皮细胞损伤是胆汁反流性胃炎最重要的病理特征之一。在中国，沉香（白木香含树脂的心材）用于治疗胃部疾病已有数千年历史。然而，胆汁酸诱导上皮细胞死亡的病理机制以及沉香改善胆汁反流性胃炎的治疗靶点尚未完全阐明。
本研究旨在探讨牛磺胆酸（TCA）通过调节内质网应激途径的促凋亡作用。此外，还证实了沉香2-(2-苯乙基)色酮富集提取物（CPE）在抑制TCA诱导的胃上皮细胞死亡中的作用。
我们采用人胃上皮GES-1细胞在体外探讨TCA诱导细胞死亡的机制。然后评估细胞活力、凋亡率和蛋白表达，以探究CPE对TCA损伤的GES-1细胞的保护作用。通过体内胆汁反流小鼠进一步证实CPE对胆汁反流性胃炎的治疗效果。
我们的结果表明，TCA通过增加半胱天冬酶-7和聚（ADP-核糖）聚合酶的裂解来激活GES-1细胞凋亡。进一步实验表明，TCA上调内质网（ER）应激，随后引发上皮细胞凋亡。我们的研究发现，CPE通过预防TCA诱导的胃上皮细胞损伤，是沉香中的主要有效成分。CPE通过抑制Perk/eIF2α/CHOP途径有效抑制TCA激活的GES-1细胞凋亡。CPE对胃黏膜的抗凋亡作用在体内也得到了证实。此外，还鉴定了CPE中对应于保护上皮细胞的主要有效成分。
我们的研究结果表明，CPE通过介导内质网应激的激活来恢复TCA诱导的上皮细胞凋亡，这为治疗胆汁反流性胃炎探索了潜在药物。
