Gallic Acid, a Methyl 3,4-Dihydroxybenzoate Derivative, Induces Neural Stem Cells to Differentiate and Proliferate

Differentiation and proliferation of neural stem cells (NSCs) are both important biological processes in cerebral neural network. However, these two capacities of NSCs are limited. Thus, the induction of differentiation and/or proliferation via administration of small molecules derived from natural plants can be considered as a potential approach to repair damaged neural networks. This paper reports that gallic acid, a catechol compound selected from derivatives of methyl 3,4-dihydroxybenzoate (MDHB), selectively induces NSCs to differentiate into immature neurons and promotes proliferation by activating phosphorylation of key proteins in the MAPK-ERK pathway. In addition, we found that 3,4-dihydroxybenzoic acid was the main active structure which could show neurotrophic activity. The substitution of carboxyl group on the benzene ring into ester group may promote differentiation on the basis of the structure of 3,4-dihydroxybenzoic acid. Meanwhile, the introduction of 5-hydroxyl group may promote proliferation. Generally, this study identified a natural catechol compound that promotes differentiation and proliferation of NSCs in vitro.