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GSH is also a natural ligand for Fe2+ in the labile iron pool (LIP), which is an exchange pool for loosely ligated iron in neurons (Hider and Kong, 2011), and glutathione binds Fe2+ in LIP to prevent iron oxidation, which not onlymaintains Fe2+ solubility but also prevents Fe2+ from acting as a catalyst to generate a potent oxidant, hydroxyl radical, from physiologically available hydrogen

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It is worth noting that the increase in Nrf2 DNA binding activity induced by berberine can be antagonized by PI3K inhibitors and AKT inhibitors

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