title: Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.
abstract: BACKGROUND
  It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration.
  
  
  METHODS
  A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation.
  
  
  RESULTS
  Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2.
  
  
  CONCLUSIONS
  We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.
authors.affiliation: The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, 840, Taiwan.|Chinese Medicine Department E-DA Hospital, Kaohsiung, 824, Taiwan.|1PT Biotechnology Co., Ltd., Taichung, 433, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Chang
authors.affiliation: Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, 404, Taiwan.|Departments of Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan.|School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Hen-Hong
authors.initials: HH
authors.lastname: Chang
authors.affiliation: The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, 840, Taiwan.|Chinese Medicine Department E-DA Hospital, Kaohsiung, 824, Taiwan.
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Division of Chinese Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan.|School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Chinese Medicine Department, China Medical University Beigang Hospital, Beigang, Yunlin, 651, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, No 91, Hsueh-Shih Road, Taichung, 404, Taiwan.
authors.forename: Chi-Xin
authors.initials: CX
authors.lastname: Ye
authors.affiliation: 1PT Biotechnology Co., Ltd., Taichung, 433, Taiwan.
authors.forename: Ping-Ling
authors.initials: PL
authors.lastname: Chiu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yueh-Sheng
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.|Graduate Institute of Basic Medical Science, China Medical University, No 91, Hsueh-Shih Road, Taichung, 404, Taiwan. cyhuang@mail.cmu.edu.tw.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. cyhuang@mail.cmu.edu.tw.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Orthopaedic Department Armed Forces General Hospital, Taichung, Taiwan.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D017451:Receptors, Somatomedin; C442779:Alpinia oxyphylla fruit extract
keywords: Alpinia oxyphylla Miq. fruit extract; IGF-1; RSC96 Schwann cell; nerve regeneration; proliferation