title: Kai-Xin-San, a standardized traditional Chinese medicine formula, up-regulates the expressions of synaptic proteins on hippocampus of chronic mild stress induced depressive rats and primary cultured rat hippocampal neuron.
abstract: BACKGROUND
  Kai-xin-san (KXS), composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, is a famous Chinese medicinal formula applied for treating stress-related psychiatric disease with the symptoms such as depression, forgetfulness and dizziness. Dependent on the symptom differentiation of patients, the composition ratio of KXS was varied and one ratio of 3:2:2:3 was widely applied. However, its molecular mechanism has seldom been investigated.
  
  
  OBJECTIVE
  We aimed to reveal the action mechanism of KXS on anti-depression on synaptic protein regulation in both in vivo and in vitro models.
  
  
  METHODS
  Firstly, the anti-depression effect of KXS was evaluated on a chronic mild stress induced depressive animal model and the mRNA expressions of various synaptic proteins in hippocampus of the depressive rat brains were determined. Then, KXS with different ratios as well as single herb were further evaluated on rat primary cultured hippocampus neurons and the possible signaling pathway was explored.
  
  
  RESULTS
  Intra-gastric administration of a chemically standardized KXS for only 6h significantly alleviated the CUMS-induced depressive symptoms displayed by enhanced sucrose consumption and this effect was maintained after daily treatment for seven days. Simultaneously, the mRNA expressions of various synaptic proteins in hippocampus were regulated. Among these synaptic proteins, synaptotagmin (pre-synaptic marker) and post synaptic density protein (post-synaptic marker), with the higher altered magnitude on animal model, were further evaluated on rat primary cultured hippocampus neurons. After neuronal cultures treated with three ratios of KXS at the early and late stages of its life episode, the expression levels of synaptotagmin and PSD95 were both enhanced dramatically via stimulating cAMP dependent pathway. However, different ratio exerted different efficacy. The ratio with higher amounts of Ginseng Radix et Rhizoma and Polygalae Radix showed better effect in early life episode while higher amounts of Acori Tatarinowii Rhizoma and Poria behaved better in late life episode. The contribution of single herb on expressions of synaptic proteins was also evaluated.
  
  
  CONCLUSIONS
  KXS was beneficial for synaptogenesis by inducing synaptic protein expressions, which might account for its anti-depression effect.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. Electronic address: zhuky@njucm.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Xiuzhu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Su
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. Electronic address: dja@njucm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
authors.affiliation: Division of Life Science and Center for Chinese Medicine, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Tina Ting-Xia
authors.initials: TT
authors.lastname: Dong
authors.affiliation: Division of Life Science and Center for Chinese Medicine, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Karl Wah-Keung
authors.initials: KW
authors.lastname: Tsim
authors.affiliation: Department of Endocrinology, Suzhou Hospital of traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Suzhou, Jiangsu Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D000242:Cyclic AMP / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000928:Antidepressive Agents; D019422:Dietary Sucrose; D004365:Drugs, Chinese Herbal; C000605449:Kai-Xin-San; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000242:Cyclic AMP
keywords: Chinese medicine; Depression; Kai-Xin-San; Synaptic protein; TCM formulae