1. Academic Validation
  2. Tanshinone IIA ameliorates Aβ transendothelial transportation through SIRT1-mediated endoplasmic reticulum stress

Tanshinone IIA ameliorates Aβ transendothelial transportation through SIRT1-mediated endoplasmic reticulum stress

  • J Transl Med. 2023 Jan 20;21(1):34. doi: 10.1186/s12967-023-03889-y.
Can Wan 1 2 3 Xiao-Qi Liu 1 2 Mei Chen 1 2 Hui-Han Ma 1 2 Guang-Liang Wu 1 2 Li-Jun Qiao 1 2 Ye-Feng Cai 4 5 Shi-Jie Zhang 6 7
Affiliations

Affiliations

  • 1 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China.
  • 2 Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, 510120, Guangzhou, China.
  • 3 Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
  • 4 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. caiyefeng@126.com.
  • 5 Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, 510120, Guangzhou, China. caiyefeng@126.com.
  • 6 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. shijiezhang@gzucm.edu.cn.
  • 7 Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, 510120, Guangzhou, China. shijiezhang@gzucm.edu.cn.
Abstract

Background: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD.

Methods: 1-42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related Enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aβ deposition respectively.

Results: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both Animals and cells.

Conclusion: Tan IIA could promote Aβ transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice.

Keywords

Aβ transportation; Brain microvascular endothelial cell; Endoplasmic reticulum stress; SIRT1; Tanshinone IIA.

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