Meng Pengfei, Yoshida Hidemi, Tanji Kunikazu, Matsumiya Tomoh, Xing Fei, Hayakari Ryo, Wang Liang, Tsuruga Kazushi, Tanaka Hiroshi, Mimura Junsei, Kosaka Kunio, Itoh Ken, Takahashi Ippei, Kawaguchi Shogo, Imaizumi Tadaatsu
Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Neurosci Res. 2015 May;94:1-9. doi: 10.1016/j.neures.2014.12.003. Epub 2014 Dec 12.
Amyloid-beta (Aβ) peptides, Aβ 1-42 (Aβ42) and Aβ43 in particular, cause neurotoxicity and cell death in the brain of Alzheimer's disease (AD) at higher concentrations. Carnosic acid (CA), a phenolic diterpene compound in the labiate herbs rosemary and sage, serves as an activator for neuroprotective and neurotrophic functions in brain cells. We investigated the effect of CA on apoptosis induced by Aβ42 or Aβ43 in cultured SH-SY5Y human neuroblastoma cells. Treatment of the cells with Aβ42 or Aβ43 (monomer, 10 μM each) induced apoptosis, which was confirmed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF). Concurrently, the Aβ treatment induced the activation of caspase (Casp) cascades including an effector Casp (Casp3) and initiator Casps (Casp4, Casp8 and Casp9). Pretreatment of the cells with CA (10 μM) partially attenuated the apoptosis induced by Aβ42 or Aβ43. CA pretreatment also reduced the cellular oligomers of Aβ42 and Aβ43. These results suggest that CA suppressed the activation of Casp cascades by reducing the intracellular oligomerization of exogenous Aβ42/43 monomer. The ingestion of an adequate amount of CA may have a potential in the prevention of Aβ-mediated diseases, particularly AD.
β淀粉样蛋白（Aβ）肽，尤其是Aβ1-42（Aβ42）和Aβ43，在较高浓度时会导致阿尔茨海默病（AD）大脑中的神经毒性和细胞死亡。迷迭香酸（CA）是唇形科草本植物迷迭香和鼠尾草中的一种酚类二萜化合物，可作为脑细胞中神经保护和神经营养功能的激活剂。我们研究了CA对培养的SH-SY5Y人神经母细胞瘤细胞中由Aβ42或Aβ43诱导的细胞凋亡的影响。用Aβ42或Aβ43（单体，各10μM）处理细胞会诱导细胞凋亡，这通过聚（ADP-核糖）聚合酶（PARP）和凋亡诱导因子（AIF）的裂解得以证实。同时，Aβ处理诱导了包括效应半胱天冬酶（Casp3）和起始半胱天冬酶（Casp4、Casp8和Casp9）在内的半胱天冬酶（Casp）级联反应的激活。用CA（10μM）对细胞进行预处理可部分减轻由Aβ42或Aβ43诱导的细胞凋亡。CA预处理还减少了Aβ42和Aβ43的细胞内寡聚体。这些结果表明，CA通过减少外源性Aβ42/43单体的细胞内寡聚化来抑制Casp级联反应的激活。摄入适量的CA可能对预防Aβ介导的疾病，尤其是AD具有潜在作用。
