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.

KEYWORDS:

• Tannic acid
• chelation
• MCAO
• neuroprotection

Acknowledgments

This work was supported by the Basic Science Research Program (NRF-2019R1F1A1058810), funded by the National Research Foundation (NRF) of Korea (to SWK) and a research grant from Inha University (INHA- 67953) (to HSK).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Inha University: [Grant Number INHA- 67953]; National Research Foundation of Korea: [Grant Number NRF-2019R1F1A1058810].