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

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(2)O(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.