Gastrodin exerts robust neuroprotection in the postischemic brain via its protective effect against Zn-toxicity and its anti-oxidative effects in astrocytes.

Gastrodin (GAS) is a predominant bioactive constituent of the Chinese herbal medicine Tianma ( 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 Zn-toxicity and its anti-oxidative effects in astrocytes. Intraperitoneal administration of GAS (40 mg/kg) after MCAO reduced mean infarct volume to 30.1 ± 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 Zn-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- Zn-toxicity and anti-oxidative effects of GAS in astrocytes. These findings indicate GAS protects astrocytes from Zn-induced toxicity and oxidative stress and these effects contribute to its neuroprotective effects in the postischemic brain.