Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling
Open Access
- 25 October 2021
- journal article
- research article
- Published by MDPI AG in Antioxidants
- Vol. 10 (11), 1678
- https://doi.org/10.3390/antiox10111678
Abstract
Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. Thunbergia laurifolia (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of T. laurifolia leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC–MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy–autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases.Funding Information
- The Overseas Research Experience Scholarship for Graduate Students, Graduate school Chulalongkorn University, Thailand (CU2019)
This publication has 86 references indexed in Scilit:
- Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathologyJournal of Psychiatry and Neuroscience, 2013
- Glutamate Induces Mitochondrial Dynamic Imbalance and Autophagy Activation: Preventive Effects of SeleniumPLOS ONE, 2012
- Mitophagy in neurodegeneration and agingFrontiers in Genetics, 2012
- Alzheimer’s Disease: The Challenge of the Second CenturyScience Translational Medicine, 2011
- The Flavanol (−)-Epicatechin Prevents Stroke Damage through the Nrf2/HO1 PathwayJournal of Cerebral Blood Flow & Metabolism, 2010
- Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2009
- AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreadingJournal of Computational Chemistry, 2009
- Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic functionEMBO Molecular Medicine, 2009
- The Nrf2–ARE PathwayAnnals of the New York Academy of Sciences, 2008
- Selective degradation of mitochondria by mitophagyArchives of Biochemistry and Biophysics, 2007