Abstract |
In this study, we investigated the mechanisms of 3',4',7-trihydroxyflavone (THF) protection of neuronal cells from neuronal cell death induced by the oxidative stress-related neurotoxin hydrogen peroxide (H2O2). Pretreatment with THF significantly elevated cell viability, reduced H2O2-induced lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, glutathione (GSH) content, superoxide dismutase (SOD) activity, catalase (CAT) activity, and mitochondria membrane potential ( MMP) loss. Western blot data demonstrated that THF inhibited the H2O2-induced up- or down-regulation of cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), Bax, Bcl-2, and Bcl-xL, and attenuated the H2O2-induced release of cytochrome c from the mitochondria to the cytosol. In addition, pretreatment with THF attenuated H2O2-induced rapid and significant phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinases (PI3K)/Akt. THF also inhibited nuclear factor-κB (NF-κB) translocation to the nucleus induced by H2O2, down-stream of H2O2-induced phosphorylation of MAPKs and PI3K/Akt. These data provide the first evidence that THF protects neuronal cells against H2O2-induced oxidative stress, possibly through ROS reduction, mitochondria protection, and NF-κB modulation via MAPKs and PI3K/Akt pathways. The neuroprotective effects of THF make it a promising candidate as a therapeutic agent for neurodegenerative diseases.
|
Authors | Seung-Hwan Kwon, Sa-Ik Hong, Shi-Xun Ma, Seok-Yong Lee, Choon-Gon Jang |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 80
Pg. 41-51
(Jun 2015)
ISSN: 1873-6351 [Electronic] England |
PMID | 25720812
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- 3',4',7-trihydroxyflavone
- Flavonoids
- Reactive Oxygen Species
- Hydrogen Peroxide
|
Topics |
- Animals
- Apoptosis
(drug effects)
- Cell Survival
(drug effects)
- Cells, Cultured
- Flavonoids
(pharmacology)
- Gene Expression Regulation
(drug effects)
- Hippocampus
(cytology)
- Hydrogen Peroxide
(toxicity)
- Neurons
(drug effects)
- Oxidative Stress
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
|