KMID : 1161520180220060429
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Animal Cells and Systems 2018 Volume.22 No. 6 p.429 ~ p.437
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Gastrodin exerts robust neuroprotection in the postischemic brain via its protective effect against Zn2+-toxicity and its anti-oxidative effects in astrocytes
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Luo Lidan
Kim Seung-Woo Lee Hye-Kyung Kim Il-Doo Lee Hahn-Bie Lee Ja-Kyeong
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Abstract
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Gastrodin (GAS) is a predominant bioactive constituent of the Chinese herbal medicine Tianma (Gastrodia elata Blume). Many authors have reported GAS has the beneficial effect on diverse diseases of the CNS, including epilepsy, Alzheimer¡¯s disease, Parkinson¡¯s disease, and cerebral ischemia. Here, we report GAS exhibited a robust neuroprotective effect in an Sprague-Dawley rat model of stroke (transient middle cerebral artery occlusion, tMCAO), and show that the underlying molecular mechanism involves its protective effect against Zn2+-toxicity and its anti-oxidative effects in astrocytes. Intraperitoneal administration of GAS (40?mg/kg) after MCAO reduced mean infarct volume to 30.1?¡¾?5.9% of that of MCAO controls and this neuroprotective effect was accompanied by neurological function recoveries which was measured using modified neurological severity score (mNSS). Interestingly, GAS induced up-regulation and nuclear translocation of Nrf2, and subsequently increased the expressions of anti-oxidative genes, such as, HO-1 and GCLM, in astrocytes. Furthermore, GAS co- or pre-treatment markedly suppressed Zn2+-induced cell death caused by excessive ROS production and PARP-1 induction. We found that GAS suppressed p67 expression and PAR formation in astrocytes, which might underlie the anti- Zn2+-toxicity and anti-oxidative effects of GAS in astrocytes. These findings indicate GAS protects astrocytes from Zn2+-induced toxicity and oxidative stress and these effects contribute to its neuroprotective effects in the postischemic brain.
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KEYWORD
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Gastrodin, MCAO, anti-Zn2+-toxicity, astrocyte, neuroprotection
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