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
  • 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.
PMID: 36903613 DOI: 10.3390/molecules28052370
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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