Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway.

Abstract

Background: Ischemic stroke is the second leading cause of death and disability worldwide, which needs to develop new pharmaceuticals for its prevention and treatment. Qingda granule (QDG), a traditional Chinese medicine formulation, could improve angiotensin II-induced brain injury and decrease systemic inflammation. In this study, we aimed to evaluate the neuroprotective effect of QDG against ischemia/reperfusion-induced cerebral injury and illustrate the potential mechanisms. Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models were established. Ischemic infarct volume was quantified using magnetic resonance imaging (MRI). Neurobehavioral deficits were assessed using a five-point scale. Cerebral histopathology was determined by hematoxylin-eosin (HE) staining. Neuronal apoptosis was evaluated by TUNEL and immunostaining with NeuN antibodies. The protective effect of QDG on OGD/R-injured HT22 cells was determined by MTT assay and Hoechst 33258 staining. The expression of lncRNA GAS5, miR-137 and apoptosis-related proteins were investigated in MCAO/R-injured rats and in OGD/R-injured HT22 cells using RT-qPCR and western blot analysis. Results: QDG significantly reduced the ischemic infarct volume, which was accompanied with improvements in neurobehavioral deficits. Additionally, QDG significantly ameliorated cerebral histopathological changes and reduced neuron loss in MCAO/R-injured rats. Moreover, QDG improved growth and inhibited apoptosis of HT22 cells injured by OGD/R in vitro. Finally, QDG significantly decreased the expression of lncRNA GAS5, Bax and cleaved caspase3, whereas it increased miR-137 and Bcl-2 expression in MCAO/R-injured rats and in OGD/R-injured HT22 cells. Conclusion: QDG plays a neuroprotective role in ischemic stroke via regulation of the lncRNA GAS5/miR-137 signaling pathway.

• Authors: Ling Zhang, Qiaoyan Cai, Shan Lin, Bin Chen, Beibei Jia, Renzhi Ye, Nathaniel Weygant, Jianfeng Chu, Jun Peng
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 18 Issue 7 Pg. 1687-1698 ( 2021) ISSN: 1449-1907 [Electronic] Australia
• PMID: 33746585 (Publication Type: Journal Article)
• Copyright: © The author(s).

Chemical References

• Drugs, Chinese Herbal
• MIRN137 microRNA, rat
• MicroRNAs
• Neuroprotective Agents
• RNA, Long Noncoding
• qingda granules

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Humans
• Ischemic Stroke (complications, drug therapy, pathology)
• Male
• Mice
• MicroRNAs (metabolism)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• RNA, Long Noncoding (metabolism)
• Rats
• Reperfusion Injury (drug therapy, etiology, pathology)
• Signal Transduction (drug effects, genetics)