1. Academic Validation
  2. The Protective Effect of (-)-Tetrahydroalstonine against OGD/R-Induced Neuronal Injury via Autophagy Regulation

The Protective Effect of (-)-Tetrahydroalstonine against OGD/R-Induced Neuronal Injury via Autophagy Regulation

  • Molecules. 2023 Mar 4;28(5):2370. doi: 10.3390/molecules28052370.
Yumei Liao 1 2 Jun-Ya Wang 3 Yan Pan 2 Xueyi Zou 2 3 Chaoqun Wang 2 Yinghui Peng 2 Yun-Lin Ao 3 Mei Fong Lam 4 Xiaoshen Zhang 1 Xiao-Qi Zhang 3 5 Lei Shi 1 2 Shiqing Zhang 2
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
  • 2 JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • 3 Guangdong Provincial Engineering Research Center for Modernization of TCM, College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • 4 Centro Hospitalar Conde de São Januário, Macau, China.
  • 5 NMPA Key Laboratory for Quality Evaluation of TCM, Jinan University, Guangzhou 510632, China.
Abstract

Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and investigated for its neuroprotective effect towards oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, primary cortical neurons were pre-treated with THA and then subjected to OGD/R induction. The cell viability was tested by the MTT assay, and the states of the autophagy-lysosomal pathway and Akt/mTOR pathway were monitored by Western blot analysis. The findings suggested that THA administration increased the cell viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal dysfunction were found at the early stage of OGD/R, which were significantly ameliorated by THA treatment. Meanwhile, the protective effect of THA was significantly reversed by the lysosome inhibitor. Additionally, THA significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R induction. In summary, THA exhibited promising protective effects against OGD/R-induced neuronal injury by Autophagy regulation through the Akt/mTOR pathway.

Keywords

(-)-Tetrahydroalstonine; Akt/mTOR; OGD/R; autophagy; cerebral ischemia.

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