A Modified Chinese Herbal Decoction (Kai-Xin-San) Promotes NGF-Induced Neuronal Differentiation in PC12 Cells via Up-Regulating Trk A Signaling.

Lu Yan,Pingping Song,Aizhen Xiong,Sherry L. Xu,Jianshu Lou,Amy G. Gong,Min Wei,Cathy W. Bi,Tina T. Dong,Karl W. Tsim

doi:10.3389/fcell.2017.00118

Abstract

Kai-Xin-San (KXS), a Chinese herbal decoction, has been applied to medical care of depression for thousands of years. It is composed of two functional paired-herbs: Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The compatibility of the paired-herbs has been frequently changed to meet the criteria of syndrome differentiation and treatment variation. Currently, a modified KXS (namely KXS2012) was prepared by optimizing the combinations of GR-PR and ATR-PO: the new herbal formula was shown to be very effective in animal studies. However, the cellular mechanism of KXS2012 against depression has not been fully investigated. Here, the study on KXS2012-induced neuronal differentiation in cultured PC12 cells was analyzed. In PC12 cultures, single application of KXS2012 showed no effect on the neuronal differentiation, but which showed robust effects in potentiating nerve growth factor (NGF)-induced neurite outgrowth and neurofilament expression. The potentiating effect of KXS2012 was mediated through NGF receptor, tropomyosin receptor kinase (Trk) A: because the receptor expression and activity was markedly up-regulated in the presence of KXS2012, and the potentiating effect was blocked by k252a, an inhibitor of Trk A. Our current results in cell cultures fully support the therapeutic efficacy of KXS2012 against depression.

Highlights

Depression, namely major depressive disorder, is a serious mental illness characterized by constant feeling of low mood, low self-esteem, and loss of interest or pleasure (Barlow and Durand, 2011; Ferrari and Villa, 2016)
KXS2012 was referring to a mixture of Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) extract plus Acori Tatarinowii Rhizoma (ATR)-PO extract at 1:5 weight ratio
In the presence of K252a (0.1 μM), the protein expression of NF68 was totally decreased to that of control in KXS2012-treated cultures (Figure 7), which suggested that KXS2012-promoted neuronal differentiation was mediated by tropomyosin receptor kinase (Trk) A. These findings suggested that KXS2012 promoted neuronal differentiation by up-regulating Trk A expression, which could increase the cellular response to low level of nerve growth factor (NGF)

Summary

Introduction

Depression, namely major depressive disorder, is a serious mental illness characterized by constant feeling of low mood, low self-esteem, and loss of interest or pleasure (Barlow and Durand, 2011; Ferrari and Villa, 2016). The major pathological alteration of depression includes neuron reduction, disorder in neurotransmitter system and loss of neurotrophic factors; these changes are more robust in hippocampus and cortex (Krishnan and Nestler, 2008; Masi and Brovedani, 2011). Anti-depressants targeted on regulating neurotransmitter levels are not able to exert an effect to all the patients, indicating the complex pathogenesis during. Neuronal differentiation having the neurite outgrowth is of great importance for brain function and low mood regulation. The induction of neuronal differentiation predicts a novel and effective therapeutic target for development of anti-depressants (Qin et al, 2008)

Methods

Results

Conclusion