Salidroside attenuates hypoxia/reoxygenation‑induced human brain vascular smooth muscle cell injury by activating the SIRT1/FOXO3α pathway

Xu,Lina; Jia,Longbin; Wang,Qingyun; Hou,Jing; Li,Shifang; Teng,Junfang

doi:10.3892/etm.2017.5446

Salidroside attenuates hypoxia/reoxygenation‑induced human brain vascular smooth muscle cell injury by activating the SIRT1/FOXO3α pathway

Authors:
- Lina Xu
- Longbin Jia
- Qingyun Wang
- Jing Hou
- Shifang Li
- Junfang Teng
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Affiliations: Department of Neurology, Jincheng People's Hospital, Jincheng, Shanxi 048026, P.R. China, Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/etm.2017.5446
Pages: 822-830
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that salidroside (SAL), a natural dietary isothiocyanate, exhibits neuroprotective roles in cerebral ischemia‑reperfusion injury. However, to the best of our knowledge, its underlying protective mechanism remains unknown. Sirtuin 1 (SIRT1) is a class III histone deacetylase involved in a variety of cellular functions. SIRT1 has been identified as a mediator of cerebral ischemia and may induce neuroprotection by activating various intracellular downstream targets, such as forkhead box protein O3α (FOXO3α). Therefore, the present study aimed to investigate whether SAL protects human brain vascular smooth muscle cells (HBVSMC) against hypoxia/reoxygenation (H/R) injury, which is a cell model of cerebral ischemia‑reperfusion injury, through regulating the SIRT1‑activited signaling pathway. The present study revealed that H/R treatment significantly reduced the expression of SIRT1 protein in HBVSMCs. Additionally, pretreatment with SAL reversed the H/R‑induced decrease in cellular viability, increased caspase‑3 activity, the appearance of apoptotic cells and the apoptosis rate in HBVSMCs. SAL attenuated the H/R‑induced decrease in the expression of SIRT1 and phosphorylated FOXO3α protein in HBVSMCs, suggesting that the protective role of SAL in H/R injury occurs via the SIRT1/FOXO3α pathway. Furthermore, sirtinol, a SIRT1‑specific inhibitor, suppressed the inhibitory effects of SAL on H/R‑induced cytotoxicity and apoptosis as indicated by the downregulation of cell viability and upregulation of caspase‑3 activity and apoptosis rate induced by sirtinol treatment in HBVSMCs. The reversal effects of SAL on H/R‑induced alternation of B‑cell lymphoma (Bcl‑2) and Bcl‑2 associated X protein expression were also attenuated by sirtinol. These results suggest that SAL exhibits neuroprotective effects against H/R injury by activating the SIRT1/FOXO3α pathway, which may become a novel potential therapeutic target for the treatment of cerebral ischemic disease.

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