Neuroprotective effects of tannic acid in the postischemic brain via direct chelation of Zn.

Tannic acid (TA) is a polyphenolic compound that exerts protective effects under pathological conditions. The diverse mechanisms of TA can exert beneficial anti-oxidative, anti-inflammatory, and anti-cancer effects. Herein, we reported that TA affords robust neuroprotection in an animal model of stroke (transient middle cerebral artery occlusion; tMCAO) and exhibits Zn-chelating and anti-oxidative effects in primary cortical neurons. Following tMCAO induction, intravenous administration of TA (5 mg/kg) suppressed infarct formation by 32.9 ± 16.2% when compared with tMCAO control animals, improving neurological deficits and motor function. We compared the chelation activity under several ionic conditions and observed that TA showed better Zn chelation than Cu. Furthermore, TA markedly decreased lactate dehydrogenase release following acute Zn treatment and subsequently reduced the expression of p67 (a cytosolic component of NADPH oxidase), indicating the potential mechanism underlying TA-mediated Zn chelation and anti-oxidative effects in primary cortical neurons. These findings suggest that anti-Zn toxicity and anti-oxidative effects participate in the TA-mediated neuroprotective effects in the postischemic brain.