State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China; School of Pharmacy, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China.
Eur J Pharmacol. 2022 Jun 15;925:174990. doi: 10.1016/j.ejphar.2022.174990. Epub 2022 Apr 29.
Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.
越来越多的证据表明，生姜及其辛辣成分具有丰富的生物活性，包括抗癌化学预防活性。然而，与其他生姜辛辣成分（如[6]-姜烯酚（6S））相比，相对较少的研究关注[6]-去氢姜酚（6-DHS）。在这项工作中，我们选择了三种生姜化合物，6-DHS、6S 和[6]-对甲氧基姜酚（6P），它们的区别在于迈克尔受体单元的存在和数量，以探讨 6-DHS 抑制血管生成的结构基础和机制，血管生成是肿瘤生长和转移的关键步骤。结果发现，它们的抗血管生成活性显著依赖于迈克尔受体单元的存在和数量。由于其两个迈克尔受体单元的存在，6-DHS 是硫氧还蛋白还原酶的最强抑制剂和谷胱甘肽的耗竭剂，因此是活性氧的最有效产生剂，这也是其抑制血管生成能力最强的原因。这项工作强调了 6-DHS 是一种依赖迈克尔受体的促氧化血管生成抑制剂。
