ABSTRACT: Neural stem cell (NSC) differentiation and proliferation are important biological processes in the cerebral neural network. However, these two abilities of NSCs are limited. Thus, the induction of differentiation and/or proliferation through the administration of plant-derived small-molecule compounds could be used to repair damaged neural networks. The present study reported that gallic acid (GA), an important phenolic acid found in tea, selectively caused NSCs to differentiate into immature neurons and promoted NSC proliferation by activating the mitogen-activated protein kinase/ extracellular-regulated kinase (MAPK/ ERK) pathway. In addition, it was found that 3,4-dihydroxybenzoic acid was the main active structure exhibiting neurotrophic activity. The substitution of the carboxyl group on the benzene ring with the ester group may promote differentiation based on the structure of 3,4 dihydroxybenzoic acid. Furthermore, the introduction of the S-hydroxyl group may promote proliferation. The present study identified that GA can promote the differentiation and proliferation of NSCs in vitro and exert pharmacological activity on NSCs.

KEYWORDS: NSCs, gallic acid, catechol, differentiation, proliferation, ERK1/2