title: Optimizing the compatibility of paired-herb in an ancient Chinese herbal decoction Kai-Xin-San in activating neurofilament expression in cultured PC12 cells.
abstract: BACKGROUND
  Kai-Xin-San (KXS), a well-known traditional Chinese herbal decoction, has been widely used to treat mental depression and memory loss in China. It has a combination of four herbs: Ginseng Radix et Rhizoma (GR; root and rhizome of Panax ginseng C. A. Mey.), Polygalae Radix (PR; root of Polygala tenuifolia Wild.), Acori Tatarinowii Rhizoma (ATR; rhizome of Acorus tatarinowii Schott), and Poria (PO; sclerotium of Poriacocos (Schw.) Wolf), from which a pairing of two herbs was considered as paired-herb, such as the pairing of GR-PR and ATR-PO. The depression-induced neural cell loss is one of the major pathogenesis in depression. Here, an optimized KXS by changing the ratio of paired-herbs in KXS was demonstrated aiming at promoting neural cell differentiation.
  
  
  METHODS
  Quantitative assessment of chemical markers in each herbal extract was determined by LC-MS. Promoters of neurofilaments, NF68 and NF200, linked with luciferase reporter gene (pNF68-Luc and pNF200-Luc) were applied in cultured pheochromocytoma (PC12) cells to study the transcriptional activation of each herbal extract. The effect of GR-PR and ATR-PO in improving NF promoter activity was analyzed by Compusyn software. The activation of PKA was indicated.
  
  
  RESULTS
  In PC12 cells, an optimized KXS named KXS1:5 having 1:5 of GR-PR:ATR-PO had greater capability in promoting the expression of neurofilament. The synergistic effect of GR-PR and ATR-PO on the improved efficiency was further determined. Moreover, the treatment of H89, a PKA inhibitor, significantly inhibited the induced NF promoter activity.
  
  
  CONCLUSIONS
  These results indicated an optimized KXS by optimizing the compatibility of paired-herb and this compatibility was proven to exert synergistic effect. Moreover, the underlying mechanism was mediated by a PKA signaling pathway.
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yan
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Zhu
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Kelly Y C
authors.initials: KY
authors.lastname: Lam
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Guizhong
authors.initials: G
authors.lastname: Xin
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Maitinuer
authors.initials: M
authors.lastname: Maiwulanjiang
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Tina T X
authors.initials: TT
authors.lastname: Dong
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Huangquan
authors.initials: H
authors.lastname: Lin
authors.affiliation: Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. Electronic address: botsim@ust.hk.
authors.forename: Karl W K
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007382:Intermediate Filaments / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
chemical_list: D004365:Drugs, Chinese Herbal; C000605449:Kai-Xin-San
keywords: Kai-Xin-San; Neurofilament; Neuronal differentiation; Optimization; Paired-herb