Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Bioorg Chem. 2020 Sep;102:104131. doi: 10.1016/j.bioorg.2020.104131. Epub 2020 Jul 23.
Five terpenoids (1-5), including three new ent-kaurane diterpenoids (1-3), one new ent-rosane type diterpenoid (4) and one known triterpenoid (5), were isolated from stigma maydis (Zea mays L.). The structures of the compounds were elucidated by comprehensive spectroscopic analyses. The relative configurations of stigmanes A-D (1-4) were determined by NOESY experiments. In addition, the relative configuration of stigmane D (4) was further established by NMR calculations. The absolute configurations of these compounds were identified by a comparison of experimental and calculated specific rotations. The neuroprotective effects of these compounds against HO-induced injury in human neuroblastoma SH-SY5Y cells were evaluated, and the results showed that among the compounds, 2 exhibited the most significant neuroprotection. Further study demonstrated that 2 could activate nuclear factor E2-related factor (Nrf2), downregulate apoptosis and reactive oxygen species (ROS) generation, and increase antioxidant enzyme activities in SH-SY5Y cells. However, the neuroprotective effect was reversed when Nrf2 was silenced. In conclusion, this study suggested that terpenoids from stigma maydis exerted neuroprotective effects through Nrf2 activation.
从玉米柱头中分离得到了 5 个三萜类化合物（1-5），包括 3 个新的贝壳杉烷二萜（1-3）、1 个新的贝壳杉烷型二萜（4）和 1 个已知的三萜（5）。通过综合光谱分析阐明了这些化合物的结构。通过 NOESY 实验确定了 stigmanes A-D（1-4）的相对构型。此外，通过 NMR 计算进一步确定了 stigmane D（4）的相对构型。通过比较实验和计算的比旋光度确定了这些化合物的绝对构型。评价了这些化合物对 HO 诱导的人神经母细胞瘤 SH-SY5Y 细胞损伤的神经保护作用，结果表明，在这些化合物中，2 表现出最显著的神经保护作用。进一步的研究表明，2 可以激活核因子 E2 相关因子（Nrf2），下调凋亡和活性氧（ROS）的产生，并增加 SH-SY5Y 细胞中的抗氧化酶活性。然而，当 Nrf2 被沉默时，神经保护作用被逆转。总之，本研究表明，玉米柱头中的三萜类化合物通过激活 Nrf2 发挥神经保护作用。
