School of Pharmacy, Anhui Medical University, Hefei, China.
The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Toxicol Mech Methods. 2022 Oct;32(8):580-587. doi: 10.1080/15376516.2022.2057263. Epub 2022 Apr 7.
The gastrointestinal side effects of mycophenolic acid affect its efficacy in kidney transplant patients, which may be due to its toxicity to the intestinal epithelial mechanical barrier, including intestinal epithelial cell apoptosis and destruction of tight junctions. The toxicity mechanism of mycophenolic acid is related to oxidative stress-mediated, the activation of mitogen-activated protein kinases (MAPK). Schisandrin A (Sch A), one of the main active components of the Schisandra chinensis, can protect intestinal epithelial cells from deoxynivalenol-induced cytotoxicity and oxidative damage by antioxidant effects. The aim of this study was to investigate the protective effect and potential mechanism of Sch A on mycophenolic acid-induced damage in intestinal epithelial cell. The results showed that Sch A significantly reversed the mycophenolic acid-induced cell viability reduction, restored the expression of tight junction protein ZO-1, occludin, and reduced cell apoptosis. In addition, Sch A inhibited mycophenolic acid-mediated MAPK activation and reactive oxygen species (ROS) increase. Collectively, our study showed that Sch A protected intestinal epithelial cells from mycophenolic acid intestinal toxicity, at least in part, by reducing oxidative stress and inhibiting MAPK signaling pathway.
麦考酚酸的胃肠道副作用会影响其在肾移植患者中的疗效，这可能是由于其对肠道上皮机械屏障的毒性作用，包括肠道上皮细胞凋亡和紧密连接的破坏。麦考酚酸的毒性机制与氧化应激介导、丝裂原活化蛋白激酶（MAPK）的激活有关。五味子甲素（Sch A）是五味子的主要活性成分之一，具有抗氧化作用，能保护肠道上皮细胞免受脱氧雪腐镰刀菌烯醇诱导的细胞毒性和氧化损伤。本研究旨在探讨 Sch A 对麦考酚酸诱导的肠道上皮细胞损伤的保护作用及潜在机制。结果表明，Sch A 能显著逆转麦考酚酸引起的细胞活力下降，恢复紧密连接蛋白 ZO-1、occludin 的表达，并减少细胞凋亡。此外，Sch A 抑制了麦考酚酸介导的 MAPK 激活和活性氧（ROS）增加。综上所述，本研究表明，Sch A 通过降低氧化应激和抑制 MAPK 信号通路，至少部分保护肠道上皮细胞免受麦考酚酸的肠道毒性。
