Diallyl trisufide protects against oxygen glucose deprivation -induced apoptosis by scavenging free radicals via the PI3K/Akt -mediated Nrf2/HO-1 signaling pathway in B35 neural cells.

Abstract

Oxidative stress contributes to development of ischemic brain damage. Many antioxidants have been proven effective in ameliorating cerebral ischemia injury by inhibiting oxidative stress. DATS, an organosulfuric component of garlic oil, exhibits antioxidative effects. In present study, we used OGD model to investigate the neuroprotective effects of DATS and the mechanisms related to these effects. B35 neural cells exposed to OGD caused a decrease in cell viability and increases in the percentage of apoptotic cells and the level of intracellular cleaved caspase-3, all of which were markedly attenuated by DATS. Further, DATS treatment significantly increased Nrf2 expression and nuclear translocation, upregulated downstream gene HO-1 and inhibited intracellular ROS and MDA generation, all of which were markedly attenuated in cells transfected with Nrf2-specific siRNA. In addition, inhibition of PI3K/Akt signaling by PI3K-specific siRNA not only decreased the expression level of Nrf2 and HO-1 proteins, but also diminished the antioxidative and neuroprotective effect of DATS. Taken together, these results indicate that DATS protects B35 neural cells against OGD-induced cell injury by inhibiting ROS production via upregulating the PI3K/Akt-mediated Nrf2 pathway, which further activates HO-1. Based on our results, DATS may be a potential candidate for intervention in hypoxic-ischemic brain injuries such as stroke.

• Authors: Xian Hua Xu, Gai Li Li, Bing Ang Wang, Yang Qin, Shu Rong Bai, Jian Rong, Tao Deng, Qiang Li
• Journal: Brain research (Brain Res) Vol. 1614 Pg. 38-50 (Jul 21 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25896937 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Allyl Compounds
• Free Radicals
• NF-E2-Related Factor 2
• Neuroprotective Agents
• RNA, Small Interfering
• Sulfides
• diallyl trisulfide
• Heme Oxygenase-1
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Caspase 3
• Glucose

Topics

• Allyl Compounds (pharmacology)
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Free Radicals (metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glucose (deficiency)
• Heme Oxygenase-1 (metabolism)
• Hypoxia (physiopathology)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Neuroblastoma (pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics)
• RNA, Small Interfering (genetics, metabolism)
• Rats
• Signal Transduction (drug effects, genetics)
• Sulfides (pharmacology)
• Time Factors