title: Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor and orexin-B receptor messenger ribonucleic acid expression and represses mitogen-activated protein kinase signaling.
abstract: BACKGROUND
  Hypocretin (HCRT) signaling plays an important role in the pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal therapy. Our previous study showed that xingshentongqiao decoction (XSTQ) is clinically effective for the treatment of narcolepsy. To determine whether XSTQ improves narcolepsy by modulating HCRT signaling, we investigated its effects on SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1 [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved in these processes were also assessed.
  
  
  METHODS
  The effects of XSTQ on proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting kit-8 and annexin V-fluorescein isothiocyanate assays. OX1R and OX2R expression was assessed by quantitative real-time polymerase chain reaction analysis. Western blotting for mitogen-activated protein kinase (MAPK) pathway activation was performed to further assess the signaling mechanism of XSTQ.
  
  
  RESULTS
  XSTQ reduced the proliferation and induced apoptosis of SH-SY5Y cells. This effect was accompanied by the upregulation of OX1R and OX2R expression and the reduced phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and c-Jun N-terminal kinase (JNK).
  
  
  CONCLUSIONS
  XSTQ inhibits proliferation and induces apoptosis in SH-SY5Y cells. XSTQ also promotes OX1R and OX2R expression. These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK signaling pathways. These results define a molecular mechanism for XSTQ in regulating HCRT and MAPK activation, which may explain its ability to treat narcolepsy.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Dong
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Wang
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Dong
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D064446:Orexin Receptors / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004365:Drugs, Chinese Herbal; D064446:Orexin Receptors; D020928:Mitogen-Activated Protein Kinases