Laboratory of Neuroscience.
Department of Traditional Chinese Medicine, College of Medicine, Dalian University, Dalian, People's Republic of China.
Neuroreport. 2020 Feb 5;31(3):245-250. doi: 10.1097/WNR.0000000000001398.
Amyloid beta (Aβ) neurotoxicity plays a causative role in the pathogenesis of Alzheimer's disease. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. In our previous study, a sesquiterpenoid compound 2β-hydroxy-δ-cadinol (HOC) which exhibited antiglutamate excitotoxicity effect was isolated from the fruits of Alpinia oxyphylla Miquel. Based on the antiglutamate excitotoxicity effect of HOC, in this study, we investigated the potential benefit of HOC in preventing Aβ(1-42)-induced neuronal apoptosis in cultured rat hippocampal neurons. The neuroprotective effect of HOC against Aβ(1-42)-induced neuronal apoptosis was assessed by Hoechst 33258 staining, reactive oxygen species (ROS) production, caspase-3 activation and caspase-3 activity. Results demonstrated that HOC treatment significantly prevented Aβ(1-42)-induced neuronal apoptosis. The underlying molecular mechanisms of HOC in preventing Aβ(1-42)-induced neuronal apoptosis may be via inhibiting Aβ(1-42)-induced ROS production, attenuating Aβ(1-42)-induced caspase-3 activation and inhibiting caspase-3 activity. This study suggests that HOC may be a potential agent for the prevention of Aβ neurotoxicity.
淀粉样蛋白 β（Aβ）神经毒性在阿尔茨海默病的发病机制中起因果作用。越来越多的证据表明，Aβ神经毒性是由谷氨酸兴奋性毒性介导的。在我们之前的研究中，从益智果实中分离出一种具有抗谷氨酸兴奋性毒性作用的倍半萜化合物 2β-羟基-δ-卡杜醇（HOC）。基于 HOC 的抗谷氨酸兴奋性毒性作用，在本研究中，我们研究了 HOC 在预防培养的大鼠海马神经元中 Aβ（1-42）诱导的神经元凋亡中的潜在益处。通过 Hoechst 33258 染色、活性氧（ROS）产生、半胱天冬酶-3 激活和半胱天冬酶-3 活性评估 HOC 对 Aβ（1-42）诱导的神经元凋亡的神经保护作用。结果表明，HOC 处理可显著预防 Aβ（1-42）诱导的神经元凋亡。HOC 预防 Aβ（1-42）诱导的神经元凋亡的潜在分子机制可能是通过抑制 Aβ（1-42）诱导的 ROS 产生、减轻 Aβ（1-42）诱导的半胱天冬酶-3 激活和抑制半胱天冬酶-3 活性。本研究表明，HOC 可能是预防 Aβ 神经毒性的潜在药物。
