Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, People's Republic of China.
Food Chem Toxicol. 2012 Jun;50(6):1927-32. doi: 10.1016/j.fct.2012.03.059. Epub 2012 Mar 23.
Eriodictyol-7-O-glucoside, a flavonoid isolated from Dracocephalum rupestre, is among the most potent free radical scavenger. In the present study, we identified eriodictyol-7-O-glucoside as a novel nuclear factor E2-related factor 2 (Nrf2) activator using a high-throughput cellular screening method. This compound activated Nrf2 signaling pathway and was able to stabilize Nrf2 by delaying Nrf2 degradation, resulting in accumulation of Nrf2 protein and activation of the Nrf2-dependent protective response. Recent studies have suggested that activation of Nrf2 pathway would confer protection against cisplatin-induced toxicity. The protective role of eriodictyol-7-O-glucoside in cisplatin-induced toxicity was investigated in a human renal mesangial cell line, HRMC. Cotreatment of HRMC cells with eriodictyol-7-O-glucoside significantly improved cell survival under cisplatin exposure. These findings demonstrated the feasibility of using natural compounds targeting Nrf2 as a therapeutic approach to subvert the side effects of cisplatin in normal cells.
从荆芥中分离得到的黄烷酮类化合物——圣草次苷，是一种最有效的自由基清除剂。本研究采用高通量细胞筛选方法，首次鉴定出圣草次苷是一种新型核因子 E2 相关因子 2（Nrf2）激活剂。该化合物可激活 Nrf2 信号通路，并通过延缓 Nrf2 降解来稳定 Nrf2，导致 Nrf2 蛋白积累和 Nrf2 依赖性保护反应的激活。最近的研究表明，激活 Nrf2 通路可对抗顺铂诱导的毒性。本研究采用人肾小球系膜细胞（HRMC），探讨了圣草次苷对顺铂诱导毒性的保护作用。与顺铂共处理 HRMC 细胞可显著提高细胞在顺铂暴露下的存活率。这些发现表明，针对 Nrf2 的天然化合物作为一种治疗方法，可用于减轻顺铂对正常细胞的副作用，具有一定的可行性。
