Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
J Ethnopharmacol. 2013 Jan 9;145(1):261-8. doi: 10.1016/j.jep.2012.10.061. Epub 2012 Nov 16.
Polygonum multiflorum has traditionally had wide use as an anti-aging treatment in East Asian countries. We investigated the neuroprotective effects of Polygonum multiflorum against glutamate-induced neurotoxicity with a focus on the anti-apoptotic mechanism in primary cultured cortical neurons.
Cell viability, cytotoxicity, morphological, flow cytometry, Western blot, and caspase activity assays were performed for examination of the neuroprotective effects of active hexane extract from Polygonum multiflorum (HEPM).
Pretreatment with HEPM resulted in significantly decreased glutamate-induced neurotoxicity in a concentration-dependent manner and also resulted in drastically inhibited glutamate-induced apoptosis. Treatment with HEPM resulted in decreased expression of glutamate-induced death receptor (DR)4, and enhanced expression of glutamate-attenuated anti-apoptotic proteins, including Bcl-2, XIAP, and cIAP-1, and slightly reduced glutamate-induced cleavage of Bid. In addition, treatment with HEPM resulted in suppressed glutamate-induced activation of caspase-8, caspase-9, and caspase-3, and, subsequently, decreased degradation of poly(ADP-ribose) polymerase, β-catenin, and phospholipase Cγ1 protein, which are downstream targets of activated caspase-3.
The results of this study demonstrated that HEPM exerts a neuroprotective effect against glutamate-induced neurotoxicity via inhibition of apoptosis. This protection may be mediated through suppression of DR4 and up-regulation of Bcl-2, XIAP, and cIAP-1, as well as inhibition of caspase activation, resulting in prevention of apoptosis of cortical neurons.
何首乌在东亚国家传统上被广泛用作抗衰老治疗方法。我们研究了何首乌对谷氨酸诱导的神经毒性的神经保护作用，重点是在原代皮质神经元中的抗细胞凋亡机制。
通过细胞活力、细胞毒性、形态学、流式细胞术、Western blot 和半胱氨酸天冬氨酸蛋白酶（caspase）活性测定来检查何首乌活性己烷提取物（HEPM）的神经保护作用。
HEPM 的预处理以浓度依赖性方式显著降低了谷氨酸诱导的神经毒性，并且还明显抑制了谷氨酸诱导的细胞凋亡。HEPM 处理导致谷氨酸诱导的死亡受体（DR）4 的表达降低，而增强了谷氨酸减弱的抗凋亡蛋白的表达，包括 Bcl-2、XIAP 和 cIAP-1，并轻微降低了谷氨酸诱导的 Bid 切割。此外，HEPM 处理抑制了谷氨酸诱导的半胱天冬氨酸蛋白酶（caspase）-8、caspase-9 和 caspase-3 的激活，随后降低了聚（ADP-核糖）聚合酶、β-连环蛋白和磷脂酶 Cγ1 蛋白的降解，这些都是激活的 caspase-3 的下游靶标。
这项研究的结果表明，HEPM 通过抑制细胞凋亡对谷氨酸诱导的神经毒性发挥神经保护作用。这种保护可能是通过抑制 DR4 和上调 Bcl-2、XIAP 和 cIAP-1 以及抑制半胱天冬氨酸蛋白酶的激活来介导的，从而防止皮质神经元的凋亡。
