Xingshentongqiao Decoction Mediates Proliferation, Apoptosis, Orexin-A Receptor and Orexin-B Receptor Messenger Ribonucleic Acid Expression and Represses Mitogen-activated Protein Kinase Signaling  

作　　者：Yuanli Dong Mei Li Shaojie Wang Yuwei Dong Hongxia Zhao Zhong Dai 

机构地区：[1]Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing 100044, China [2]Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing 100044, China [3]Department of Traditional Chinese Medicine, Hospital of Mentougou District of Beijing City, Beijing 102300, China

出　　处：《Chinese Medical Journal》2015年第1期98-104,共7页中华医学杂志（英文版）

摘　　要：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 [OXl R] 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 OX 1R 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 Erkl/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.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 [OXl R] 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 OX 1R 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 Erkl/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.

关 键 词：Hypocretin Signaling Mitogen-activated Protein Kinases Narcolepsy： Traditional Chinese Medicine Xingshentongqiao Decoction 

分 类 号：Q26[生物学—细胞生物学] Q253