DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways

• Main Authors: Qingxia Huang (Author), Tianye Lan (Author), Jing Lu (Author), He Zhang (Author), Dongmei Zhang (Author), Tingting Lou (Author), Peng Xu (Author), Jixiang Ren (Author), Daqing Zhao (Author), Liwei Sun (Author), Xiangyan Li (Author), Jian Wang (Author)
• Format: Book
• Published: Frontiers Media S.A., 2018-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

DiDang Tang (DDT), a Chinese traditional medicine formula, contains 4 Chinese traditional medicine substances, has been widely used to treat intracerebral hemorrhage (ICH) patients. However, the molecular mechanisms of DDT for protecting neurons from oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress and apoptosis after ICH still remains elusive. In this study, high-performance liquid chromatography fingerprint analysis was performed to learn the features of the chemical compositions of DDT. OGD-induced ER stress, Ca2+ overload, and mitochondrial apoptosis were investigated in nerve growth factor -induced PC12, primary neuronal cells, and ICH rats to evaluate the protective effect of DDT. We found that DDT treatment protected neurons against OGD-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. DDT decreased OGD-induced Ca2+ overload and ER stress through the blockade of the glucose-regulated protein 78 (GRP78)- inositol-requiring protein 1α (IRE1)/ protein kinase RNA-like ER kinase (PERK) pathways and also inhibited apoptosis by decreasing mitochondrial damage. Moreover, we observed similar findings when we studied DDT for inhibition of ER stress in a rat model of ICH. In addition, our experiments further confirmed the neuroprotective potential of DDT against tunicamycin (TM)-induced neural damage. Our in vitro and in vivo results indicated that the neuroprotective effect of DDT against ER stress damage and apoptosis occurred mainly by blocking the GPR78-IRE1/PERK pathways. Taken together, it provides reliable experimental evidence and explains the molecular mechanism of DDT for the treatment of patients with ICH.

Item Description

1663-9812
10.3389/fphar.2018.01423