Neuroprotective effects of tannic acid in the postischemic brain via direct chelation of Zn2.

Abstract

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 Zn²⁺-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 Zn²⁺ chelation than Cu²⁺. Furthermore, TA markedly decreased lactate dehydrogenase release following acute Zn²⁺ treatment and subsequently reduced the expression of p67 (a cytosolic component of NADPH oxidase), indicating the potential mechanism underlying TA-mediated Zn²⁺ chelation and anti-oxidative effects in primary cortical neurons. These findings suggest that anti-Zn²⁺ toxicity and anti-oxidative effects participate in the TA-mediated neuroprotective effects in the postischemic brain.