Chen Jichao, Wang Ruifan, Wang Tianyu, Ding Qilong, Khalil Aliahmad, Xu Shengtao, Lin Aijun, Yao Hequan, Xie Weijia, Zhu Zheying, Xu Jinyi
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.
Department of Pharmacology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, P. R. China.
ACS Med Chem Lett. 2017 Mar 13;8(4):443-448. doi: 10.1021/acsmedchemlett.7b00035. eCollection 2017 Apr 13.
A series of novel β-elemene dimer derivatives were synthesized and evaluated for their antioxidant activities. The results indicated that most of the target compounds showed more potent cytoprotective effects than positive control vitamin E. In particular, dimer exhibited the strongest antioxidant activity, which was significantly superior to the active compound obtained in our previous study. Besides, did not produce obvious cytotoxicity in normal human umbilical vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by HO in a concentration-dependent manner. Further studies suggested that the cytoprotective action of might be mediated, at least in part, by increasing the intracellular superoxide dismutase activity and nitric oxide secretion as well as decreasing the intracellular malonyldialdehyde content and lactate dehydrogenase release. Furthermore, observably inhibited ROS generation and prevented HO-induced apoptosis in HUVECs possibly via inhibiting the activation of the MAPK signaling pathway.
合成了一系列新型β-榄香烯二聚体衍生物，并对其抗氧化活性进行了评估。结果表明，大多数目标化合物表现出比阳性对照维生素E更强的细胞保护作用。特别是，二聚体表现出最强的抗氧化活性，明显优于我们先前研究中获得的活性化合物。此外，在正常人脐静脉内皮细胞（HUVECs）中未产生明显的细胞毒性，并以浓度依赖的方式提高了受HO损伤的HUVECs的活力。进一步的研究表明，其细胞保护作用可能至少部分是通过增加细胞内超氧化物歧化酶活性和一氧化氮分泌，以及降低细胞内丙二醛含量和乳酸脱氢酶释放来介导的。此外，可能通过抑制MAPK信号通路的激活，明显抑制HUVECs中ROS的产生并防止HO诱导的细胞凋亡。
