Extractive from Hypericum ascyron L promotes serotonergic neuronal differentiation in vitro

Background: Plant natural products have many different biological activities but the precise mechanisms underlying these activities remain largely unknown. Hypericum longistylum has long been recorded in Chinese medicine as a cure for depression and related disorders, but how it repairs neural lineages has not been addressed. Methods: We extracted compounds from Hypericum longistylum and determined their effect on neural differentiation of embryonic stem cells (ESCs) in vitro by using the Pax6-GFP reporter system. The amount of serotonin released during differentiation was measured by HPLC. The tail suspension test and forced swimming test was performed for determining the effect of compounds on depression-like behaviors in mice. Results: We found that one of the phloroglucinol derivatives not only facilitated differentiation of neural progenitor cells, but also increased the efficiency of differentiation into serotonergic neurons. This compound also improved the behaviors of mice placed in a stressful environment and reduced signs of depression. Conclusions: This is the first use of Chinese herb derived-natural products to promote neurogenesis of ESCs, including the generation of serotonergic neurons, and the first attempt to identify the active compound in Hypericum longistylum responsible for its beneficial effects on depressive diseases. Keywords: Cell differentiation, Chemical modification, Depression, Chinese medicine, Neural differentiation, Serotonergic neuron