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赛络通预防过氧化氢(H₂O₂)诱导的EA.hy926细胞损伤。

Sailuotong Prevents Hydrogen Peroxide (H₂O₂)-Induced Injury in EA.hy926 Cells.

作者信息

Seto Sai Wang, Chang Dennis, Ko Wai Man, Zhou Xian, Kiat Hosen, Bensoussan Alan, Lee Simon M Y, Hoi Maggie P M, Steiner Genevieve Z, Liu Jianxun

机构信息

National Institute of Complementary Medicine (NICM), Western Sydney University, Penrith, NSW 2571, Australia.

Faculty of Medicine, University of New South Wales, NSW 2052, Australia.

出版信息

Int J Mol Sci. 2017 Jan 5;18(1):95. doi: 10.3390/ijms18010095.

Abstract

Sailuotong (SLT) is a standardised three-herb formulation consisting of , , and designed for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H₂O₂)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1-50 µg/mL) significantly suppressed the H₂O₂-induced cell death and abolished the H₂O₂-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H₂O₂ (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1-50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H₂O₂-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H₂O₂-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed.

摘要

参龙通(SLT)是一种标准化的三味草药配方,由[此处草药名称缺失]、[此处草药名称缺失]和[此处草药名称缺失]组成,用于治疗血管性痴呆。虽然最新的临床试验已证明SLT对血管性痴呆有有益作用,但其潜在的细胞机制尚未得到充分探索。本研究的目的是评估SLT对抗过氧化氢(H₂O₂)诱导的人血管内皮细胞(EAhy926)氧化损伤的能力和机制。SLT(1 - 50 µg/mL)以浓度依赖性方式显著抑制H₂O₂诱导的细胞死亡,并消除H₂O₂诱导的活性氧(ROS)生成。同样,H₂O₂(0.5 mM;24小时)使EA.hy926细胞的乳酸脱氢酶(LDH)释放增加约2倍,而SLT(1 - 50 µg/mL)以浓度依赖性方式显著抑制了这种增加。SLT(50 µg/mL)孵育可增加超氧化物歧化酶(SOD)活性,并抑制H₂O₂增强的Bax/Bcl - 2比值和裂解的半胱天冬酶 - 3表达。总之,我们的结果表明,SLT通过直接减少细胞内ROS生成和增加SOD活性来保护EA.hy916细胞免受H₂O₂介导的损伤。这些保护作用与通过抑制半胱天冬酶 - 3激活和降低Bax/Bcl - 2比值来抑制凋亡死亡级联反应密切相关,从而表明了观察到的临床效果的潜在作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/834f/5297729/cfd289da0e3a/ijms-18-00095-g003.jpg

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