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Gastrodin Alleviates Cerebral Ischemic Damage in Mice by Improving Anti-oxidant and Anti-inflammation Activities and Inhibiting Apoptosis Pathway

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Abstract

Gastrodin (GAS), an active constituent of the Chinese herbal medicine Tianma, has anti-oxidant and anti-inflammation activities but its protective effect to the prevention of neurotoxicity induced by ischemic stroke is unclear. In the present study, middle cerebral artery occlusion (MCAO) was used to establish a mice ischemic stroke model. Infarct volume ratio and neurobehavioral score were evaluated, Nissl staining was performed and the expression of cleaved Caspase 3, Bax and B cell lymphoma 2 (Bcl-2) were assessed at 24 h or 7 days after reperfusion. In addition, the total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, as well as the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD1, phospho-Akt and total Akt and TNF-α and IL-1β in the ischemic hemispheres were also observed at 6 h after reperfusion to assess oxidative stress and inflammatory changes after GAS treatment. It was found that GAS, especially at high dose (100 mg/kg) reduced tested neuronal injury and neurobehavioral deficient in MCAO mice. Enhanced expression of cleaved Caspase 3 and Bax and decreased expression of Bcl-2 by MCAO were also reversed by GAS. Moreover, GAS treatment decreased the MDA content and the expression of TNF-α and IL-1β, and increased amount of SOD activity and the expression of HO-1 and SOD1 in GAS-treated ischemic brain. Furthermore, GAS significantly increased Akt phosphorylation and Nrf2 expression. These results support the neuroprotective effects of GAS, and the activation of Akt/Nrf2 pathway may play a critical role in the pharmacological action of GAS.

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Abbreviations

GAS:

Gastrodin

Nrf2:

Nuclear factor erythroid 2-related factor 2

TNF-α:

Tumor necrosis factor-α

IL-1β:

Interleukin-1β

ROS:

Reactive oxygen species

CAT:

Catalase

SOD:

Superoxide dismutase

MCAO:

Middle cerebral artery occlusion

PI3-K:

Phosphatidylinositol 3-kinase

HO-1:

Heme oxygenase-1

MDA:

Malondialdehyde

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (Grant No. 81401109, 81171285 and 81371478) and No. 13QNP28, Youth Training Project of the Health Department of General Logistics Department to Dr. Jiao Deng.

Conflict of interest

The authors declared that there are no conflicts of interest.

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    Authors and Affiliations

    1. Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, 710032, China

      Zhengwu Peng, Rui Liu, Jiangzheng Liu, Tao Zhang & Chunxu Hai

    2. Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

      Zhengwu Peng, Guanjie Chen, Min cai & Qingrong Tan

    3. Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

      Shiquan Wang & Jiao Deng

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    Correspondence to Qingrong Tan or Chunxu Hai.

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    Zhengwu Peng, Shiquan Wang and Guanjie Chen has contributed equally to this work.

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    Peng, Z., Wang, S., Chen, G. et al. Gastrodin Alleviates Cerebral Ischemic Damage in Mice by Improving Anti-oxidant and Anti-inflammation Activities and Inhibiting Apoptosis Pathway. Neurochem Res 40, 661–673 (2015). https://doi.org/10.1007/s11064-015-1513-5

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