A Chinese herbal decoction, reformulated from Kai-Xin-San, relieves the depression-like symptoms in stressed rats and induces neurogenesis in cultured neurons

Abstract

Kai-Xin-San (KXS), a Chinese herbal decoction for anti-depression, is a combination of paired-herbs, i.e. Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The make-up of the paired-herbs has been commonly revised according to syndrome differentiation and treatment variation of individual. Currently, an optimized KXS (KXS ₂₀₁₂) was prepared by functional screening different combination of GR-PR and ATR-PO. The aim of this study was to verify the effect and underlying mechanism of KXS ₂₀₁₂ against depression in chronic mild stress (CMS)-induced depressive rats and in primary cultures of neurons and astrocytes. In rat model, the CMS-induced depressive symptoms were markedly alleviated by the treatment with KXS ₂₀₁₂. The CMS-suppressed neurotransmitter amounts were restored in the presence of KXS ₂₀₁₂. And the expressions of neurotropic factors and its corresponding receptors were increased under KXS ₂₀₁₂ administration. In cultured neurons, application of KXS ₂₀₁₂ could promote neurogenesis by inducing the expression of synaptotagmin and dendritic spine density. Moreover, application of KXS ₂₀₁₂ in cultured astrocytes, or in H ₂O ₂-stressed astrocytes, induced the expressions of neurotrophic factors: the increase might be associated with the modification of Erk1/2 and CREB phosphorylation. Our current results fully support the therapeutic efficacy of KXS ₂₀₁₂ against depression in cell and animal models.