Wogonin induces differentiation and neurite outgrowth of neural precursor cells

Wogonin is a flavonoid isolated from Scutellaria baicalensis root, and has multiple pharmacological effects, including anti-inflammatory, anti-oxidant, and anti-cancer effects. It is also neuroprotective in the brain under many stress conditions, but wogonin does not elevate neuronal cell survival. Thus, the mechanisms controlling the neuroprotective effect of wogonin are not clear. Neural precursor cells (NPCs), present in the hippocampus and subventricular zone of adult brains, replace damaged cells. In this study we investigated the biological functions underlying the neuroprotective effect of wogonin on NPCs. We initially examined survival of NPCs but found it was slightly reduced at concentrations higher than 2 μg/ml. When we explored differentiation of NPCs into neuronal cells, the number of differentiated cells expressing neurofilaments was increased remarkably (fourfold) in the hippocampal NPCs treated with wogonin. Wogonin maximally elevated the expressions of presynaptic protein, synapsin I and postsynaptic protein (PSD95) at a concentration of 0.7 μg/ml. Differentiated cells containing longer neurites were significantly increased in cortical NPCs, primarily cultured from rat E14 embryonic brain. Wogonin also promoted differentiation of NPCs into mature neurons in vivo. When transplanted into the adult rat hippocampus, NPCs differentiated into cells expressing NeuN, the mature neuron marker, by 4 weeks after transplantation. These data indicate that wogonin induces differentiation of NPCs both in culture and in vivo, and suggest that facilitation of NPC differentiation is a biological activity by which wogonin protects neurons in damaged brain.

Research highlights► Wogonin, a flavonoid compound, has neuroprotective effect but, we showed wogonin does not elevate cell viability of neural precursor cells or mature neurons of the rat brain. ► Wogonin is able to induce neuronal differentiation and elongation of neurite of hippocampal and cortical precursor cells cultured primarily from the rat embryo. ► We also demonstrated expression of synaptic proteins is upregulated by wogonin. ► Wogonin is able to promote neuronal differentiation of hippocampal precursor cells transplanted into the adult rat brain in vivo. ► This suggest wogonin is neuroprotective by inducing differentiation of neural precursor cells. Thus, neurons survive better by receiving target-derived survival factors through their synapse.