The Phenolic Components of Gastrodia elata improve Prognosis in Rats after Cerebral Ischemia/Reperfusion by Enhancing the Endogenous Antioxidant Mechanisms.

Anhuan Shi,Jianming Xiang,Fangyan He,Yanping Zhu,Yuhan Lin,Ningna Zhou,Gongbei Zhu

doi:10.1155/2018/7642158

Abstract

Pharmacological or spontaneous thrombolysis in ischemic stroke triggers an outbreak of reactive oxygen species and results in neuron death. Nrf2-mediated antioxidation in cells has been proved as a pivotal target for neuroprotection. This research reports that phenolic components of Gastrodia elata Blume (PCGE), a traditional Chinese medicine, can alleviate the pathological lesions in the penumbra and hippocampus by increasing the survival of neurons and astrocytes and improve neurofunction and cognition after reperfusion in a rat model of middle cerebral artery occlusion. LDH assay indicated that pretreatment of cells with PCGE (25 μg/ml) for 24 h significantly reduced H2O2-induced cell death in astrocytes and SH-SY5Y cells. Western blot showed that the nucleus accumulation of Nrf2 and the expression of cellular HO-1 and NQO-1, two of Nrf2 downstream proteins, were increased in both cells. BDNF, an Nrf2-dependent neurotrophic factor, was also upregulated by PCGE in astrocytes. These results illustrated that PCGE can reduce the cerebral ischemia/reperfusion injury and improve prognosis by remedying the cell damage within affected tissues. The protective effects of PCGE seem to be via activation of a Nrf2-mediated cellular defense system. Therefore, PCGE could be a therapeutic candidate for ischemic stroke and other oxidative stress associated neurological disorders.

Highlights

Embolic or atherothrombotic blocking to a cerebral artery is defined as ischemic stroke and accounts for 80% of all stroke cases
Dulbecco’s modified Eagle’s medium (DMEM), L-glutamine, AntibioticAntimycotic (100X), trypsin-EDTA, H2O2, and collagen were obtained from Invitrogen (Life Technologies, China)
The pathological and behavioral data from this present study indicated that phenolic components of Gastrodia elata Blume (PCGE) could alleviate pathological lesions in the penumbra by avoiding or reducing neuronal degeneration and thereupon improve the prognosis of cerebral I/R rats

Summary

Introduction

Embolic or atherothrombotic blocking to a cerebral artery is defined as ischemic stroke and accounts for 80% of all stroke cases. Tissue plasminogen activator (tPA) approved by the US Food and Drug Administration (FDA) in 1996 is still the only pharmacological intervention for acute ischemic stroke. Due to narrow eligibility and treatment windows, only 2%–5% of all stroke patients receive tPA treatment and only 50% of that achieve successful reperfusion [1]. TPA intervention increases the risk of intracerebral hemorrhage [2] and reperfusion injury [3]; the application of tPA in the clinic has been limited. Neuronal apoptosis or necrosis is an inevitable result of ischemic injury, which subsequently induces limb, language, and cognitive dysfunction, and remains a tough challenge for therapeutics. The exploration of potential therapeutic agents that may lead to a viable clinical application is needed urgently [5]

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