Zhao Zhi-Ying, Gao Yang-Yang, Gao Li, Zhang Ming, Wang He, Zhang Chun-Hong
a Department of Anatomy , Baotou Medical College , Inner Mongolia , China.
b The third affiliated hospital , Baotou Medical College , Inner Mongolia , China.
J Toxicol Environ Health A. 2017;80(22):1187-1192. doi: 10.1080/15287394.2017.1367114. Epub 2017 Sep 12.
Bellidifolin, a xanthone compound derived from plants of Gentiana species, is known to exert a variety of pharmacological activities including anti-oxidation, anti-inflammatory and antitumor actions as well as a protective effect on cerebral ischemic nerve injury. The aim of this study was to examine the protective effects of bellidifolin on nerve injury produced by hypoxia and possible underlying mechanisms using pheochromocytoma cells (PC12). Data showed that the viability of PC12 cells subjected to hypoxia resulted in a significant decrease; however; pretreatment with certain concentrations of bellidifolin (20 or 40 μmol/L) prior to hypoxia significantly increased the survival rate. The results of immunohistochemical staining analysis revealed that there were no marked alterations in the expression of pERK protein between all bellidifolin groups while the expression of p-p38MAPK protein was significantly enhanced by hypoxia. Pretreatment with different concentrations of bellidifolin followed by hypoxia significantly decreased the expression of p-p38MAPK protein. The results of western blot analysis showed that hypoxia induced the expression of the MAPK signaling pathway downstream of the key apoptosis factor caspase-3. Compared to hypoxia, the expression of caspase-3 in the presence of belliidifolin was significantly lower. Data suggest that bellidifolin may contribute to the protective effects associated with nerve injury initiated by hypoxia by mechanisms related to inhibition of cell apoptosis independent of the ERK pathway, but may involve blockade of p38MAPK signaling pathway activation and downstream caspase-3 expression.
秦艽叶苷是一种从龙胆属植物中提取的氧杂蒽酮类化合物，已知具有多种药理活性，包括抗氧化、抗炎和抗肿瘤作用，以及对脑缺血神经损伤的保护作用。本研究的目的是使用嗜铬细胞瘤细胞（PC12）研究秦艽叶苷对缺氧所致神经损伤的保护作用及其潜在机制。数据显示，缺氧处理的PC12细胞活力显著降低；然而，在缺氧前用一定浓度（20或40μmol/L）的秦艽叶苷预处理可显著提高细胞存活率。免疫组化染色分析结果显示，各秦艽叶苷组之间pERK蛋白表达无明显变化，而缺氧可显著增强p-p38MAPK蛋白的表达。用不同浓度的秦艽叶苷预处理后再进行缺氧处理，可显著降低p-p38MAPK蛋白的表达。蛋白质印迹分析结果显示，缺氧诱导关键凋亡因子caspase-3下游的MAPK信号通路表达。与缺氧组相比，在秦艽叶苷存在的情况下，caspase-3的表达显著降低。数据表明，秦艽叶苷可能通过抑制细胞凋亡的机制对缺氧引发的神经损伤起到保护作用，该机制独立于ERK途径，但可能涉及阻断p38MAPK信号通路的激活和下游caspase-3的表达。
