Int J Med Sci 2021; 18(7):1687-1698. doi:10.7150/ijms.53603

Research Paper

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

Ling Zhang1,3,4*, Qiaoyan Cai1,2,3,4*, Shan Lin1,3,4, Bin Chen5, Beibei Jia1,6, Renzhi Ye1,6, Nathaniel Weygant1,3, Jianfeng Chu1,3,4✉, Jun Peng1,3,4✉

1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou 350122, China.
2. Fujian Key Laboratory of Rehabilitation Technology, Fujian University of Traditional Chinese Medicine, Qiuyang Road, Minhou Shangjie, Fuzhou, China.
3. Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou 350122, China.
4. Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian 350122, China.
5. People's Hospital of Fujian University of Traditional Chinese Medicine, No.602, 817 Middle Road, Fuzhou 350004, China.
6. The Higher Educational Key Laboratory for Integrative Medicine of Fujian Province, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Minhou Shangjie, Fuzhou, Fujian 350122, China.
*These authors contributed equally to this work.

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Citation:
Zhang L, Cai Q, Lin S, Chen B, Jia B, Ye R, Weygant N, Chu J, Peng J. Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway. Int J Med Sci 2021; 18(7):1687-1698. doi:10.7150/ijms.53603. Available from https://www.medsci.org/v18p1687.htm

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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.

Keywords: Qingda granule, ischemic stroke, lncRNA GAS5, miR-137, neuronal apoptosis