Xu Ping, Zhang Wen-Bo, Cai Xin-Hua, Qiu Pei-Yong, Hao Ming-Hua, Lu Dan-Dan
Department of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
Synthetic Biology Remaking Engineering and Application Laboratory, Xinxiang Medical University, Xinxiang, Henan 453003, China.
Eur J Pharmacol. 2017 Jan 15;795:66-74. doi: 10.1016/j.ejphar.2016.11.052. Epub 2016 Dec 2.
Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10μg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10μg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.
放射疗法是许多肿瘤最有效的非手术治疗方法之一。然而，辐射损伤仍然是放射治疗的一个主要负面后果。目前，曲克芦丁的辐射防护作用已得到证实，但其辐射防护机制尚未阐明。在此，本研究表明曲克芦丁可保护受照射小鼠的胸腺组织，其对胸腺细胞的辐射防护作用在0.625 - 10μg/ml范围内显著。曲克芦丁在浓度为10μg/ml时可显著抑制受照射胸腺细胞的凋亡。利用计算机辅助药物设计来研究曲克芦丁的潜在候选靶点，发现曲克芦丁与AKT之间存在良好的相关性（Pharm mapper和KEGG信号通路）。曲克芦丁抑制PTEN的激活以刺激AKT，进而阻止JNK的激活以保护细胞。我们的结果表明，曲克芦丁至少部分通过激活AKT抑制JNK的激活来增强辐射防护作用。
