Guangdong Pharmaceutical University, Guangzhou, China.
Basic Clin Pharmacol Toxicol. 2013 Mar;112(3):182-5. doi: 10.1111/bcpt.12009. Epub 2012 Nov 1.
Genistein (Gen), a derivative of soy isoflavone aglycone, has been shown to exert significant protective effect on Aβ-induced neurotoxicity and neuroinjury. However, its underlying mechanism remains elusive. The objective was to investigate the inhibitory effect of Gen on Aβ-induced neurotoxicity and to elucidate the underlying mechanism. Primary rat hippocampal neurons were pre-treated with Gen for 2 hr followed by incubation with Aβ 25-35 for an additional 24 hr. The cell viability was assessed by MTT assay. The content and activity of α-, β-secretase and protein kinase C (PKC) were measured, and the antagonistic effect of PKC inhibitor Myr was also analysed to clarify the molecular mechanism of Gen inhibition of Aβ-induced toxicity to hippocampal neurons. The results showed that pre-treatment with Gen significantly increased the cell viability and presented the best effect at the final concentration of 0.375 µg/mL. Gen increases the activity of α-secretase but down-regulates the β-secretase activity. It also enhances the expression and activity of PKC. Myr, a PKC inhibitor, partially blocks the activation effect of Gen. Gen exerts protective effect on Aβ-induced neurotoxicity via activating the PKC signalling pathway, which further regulates the activities of α- and β-secretase and thereby inhibits the formation and toxicity of Aβ.
染料木黄酮（Gen）是大豆异黄酮苷元的衍生物，已被证明对 Aβ 诱导的神经毒性和神经损伤具有显著的保护作用。然而，其潜在机制仍不清楚。本研究旨在探讨 Gen 对 Aβ 诱导的神经毒性的抑制作用及其潜在机制。原代大鼠海马神经元先用 Gen 预处理 2 小时，然后再用 Aβ 25-35 孵育 24 小时。通过 MTT 法评估细胞活力。测量 α-、β-分泌酶和蛋白激酶 C（PKC）的含量和活性，并分析 PKC 抑制剂 Myr 的拮抗作用，以阐明 Gen 抑制 Aβ 诱导的海马神经元毒性的分子机制。结果表明，Gen 预处理可显著提高细胞活力，终浓度为 0.375μg/mL 时效果最佳。Gen 增加了 α-分泌酶的活性，但下调了β-分泌酶的活性。它还增强了 PKC 的表达和活性。PKC 抑制剂 Myr 部分阻断了 Gen 的激活作用。Gen 通过激活 PKC 信号通路对 Aβ 诱导的神经毒性发挥保护作用，进一步调节 α-和 β-分泌酶的活性，从而抑制 Aβ 的形成和毒性。
