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3.1.1.4 Grape seed proanthocyanidin extract (GSPE) GSPE, a natural bioactive compound from plant, exhibits great therapeutic properties through inhibiting oxidative stress and promoting mitochondrial biogenesis ( via AMPK-Sirtuin-1-PGC-1-TFAM signaling pathway ( 3.1.2 Sirtuin activators 3.1.2.1 Resveratrol Resveratrol, a natural compound extracted from the berries of Vaccinium species, can activate sirtuin-1, sirtuin-3, and sirtuin-5 (Xia et al., 2017

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Every one of these mechanistic claims, however, rests on animal and in-vitro data there is no human mechanistic confirmation