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红景天苷通过激活 ERK1/2 和 AKT 信号通路保护 PC-12 细胞免受淀粉样β诱导的细胞凋亡。

Salidroside protects PC-12 cells against amyloid β-induced apoptosis by activation of the ERK1/2 and AKT signaling pathways.

机构信息

Department of Psychiatry, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

Psychiatry and Mental Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.

出版信息

Int J Mol Med. 2019 Apr;43(4):1769-1777. doi: 10.3892/ijmm.2019.4088. Epub 2019 Feb 1.

Abstract

Alzheimer's disease (AD) is one of the most frequent diseases in elderly people and causes high mortality. Its incidence is increasing annually and no effective therapeutic treatment currently exists. In the present study, salidroside, a major active ingredient of Rhodiola rosea, was able to protect PC‑12 cells from the toxicity and apoptosis induced by AD inducer amyloid (A)β1‑42. Salidroside significantly protected PC‑12 cells by inhibiting Aβ1‑42‑induced cytotoxicity and mitochondria‑mediated endogenous caspase apoptotic pathways. Mechanistic studies demonstrated that salidroside significantly activated the extracellular signal regulated kinase (ERK)1/2 and protein kinase B (AKT) signaling pathways. This observation was further confirmed using the ERK1/2 inhibitor PD98059 and the AKT inhibitor LY294002, which demonstrated that salidroside promoted PC‑12 cell survival and proliferation by activating the ERK1/2 and AKT signaling pathways. Salidroside is a therapeutic candidate for the treatment of AD and provides a basis for further drug development.

摘要

阿尔茨海默病(AD)是老年人中最常见的疾病之一,死亡率很高。其发病率逐年上升,目前尚无有效的治疗方法。在本研究中,红景天中的主要活性成分红景天苷能够保护 PC-12 细胞免受 AD 诱导剂淀粉样蛋白(A)β1-42 的毒性和凋亡作用。红景天苷通过抑制 Aβ1-42 诱导的细胞毒性和线粒体介导的内源性半胱天冬酶凋亡途径显著保护 PC-12 细胞。机制研究表明,红景天苷显著激活细胞外信号调节激酶(ERK)1/2 和蛋白激酶 B(AKT)信号通路。使用 ERK1/2 抑制剂 PD98059 和 AKT 抑制剂 LY294002 进一步证实了这一观察结果,表明红景天苷通过激活 ERK1/2 和 AKT 信号通路促进 PC-12 细胞的存活和增殖。红景天苷是治疗 AD 的候选药物,为进一步的药物开发提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b0/6414153/974f54c6ec49/IJMM-43-04-1769-g00.jpg

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