title: Hypoglycemic effects of Trichosanthes kirilowii and its protein constituent in diabetic mice: the involvement of insulin receptor pathway.
abstract: BACKGROUND
  Diabetes is a serious chronic metabolic disorder. Trichosanthes kirilowii Maxim. (TK) is traditionally used for the treatment of diabetes in traditional Chinese medicine (TCM). However, the clinical application of TK on diabetic patients and the hypoglycemic efficacies of TK are still unclear.
  
  
  METHODS
  A retrospective cohort study was conducted to analyze the usage of Chinese herbs in patients with type 2 diabetes in Taiwan. Glucose tolerance test was performed to analyze the hypoglycemic effect of TK. Proteomic approach was performed to identify the protein constituents of TK. Insulin receptor (IR) kinase activity assay and glucose tolerance tests in diabetic mice were further used to elucidate the hypoglycemic mechanisms and efficacies of TK.
  
  
  RESULTS
  By a retrospective cohort study, we found that TK was the most frequently used Chinese medicinal herb in type 2 diabetic patients in Taiwan. Oral administration of aqueous extract of TK displayed hypoglycemic effects in a dose-dependent manner in mice. An abundant novel TK protein (TKP) was further identified by proteomic approach. TKP interacted with IR by docking analysis and activated the kinase activity of IR. In addition, TKP enhanced the clearance of glucose in diabetic mice in a dose-dependent manner.
  
  
  CONCLUSIONS
  In conclusion, this study applied a bed-to-bench approach to elucidate the hypoglycemic efficacies and mechanisms of TK on clinical usage. In addition, we newly identified a hypoglycemic protein TKP from TK. Our findings might provide a reasonable explanation of TK on the treatment of diabetes in TCM.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lo
authors.affiliation: Graduate Institute of Biostatistics, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Tsai-Chung
authors.initials: TC
authors.lastname: Li
authors.affiliation: Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, 40447, Taiwan.
authors.forename: Tse-Yen
authors.initials: TY
authors.lastname: Yang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Li
authors.affiliation: Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan.
authors.forename: Jen-Huai
authors.initials: JH
authors.lastname: Chiang
authors.affiliation: Department of Microbiology, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. cyhsiang@mail.cmu.edu.tw.
authors.forename: Chien-Yun
authors.identifier: http://orcid.org/0000-0002-6507-8015
authors.initials: CY
authors.lastname: Hsiang
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. tyh@mail.cmu.edu.tw.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan. tyh@mail.cmu.edu.tw.
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
mesh_terms: D000818:Animals; D015331:Cohort Studies; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010940:Plant Proteins / Q000627:therapeutic use; D011972:Receptor, Insulin / Q000378:metabolism*; D012189:Retrospective Studies; D013624:Taiwan; D029778:Trichosanthes / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D010940:Plant Proteins; D011972:Receptor, Insulin
keywords: Diabetes; Hypoglycemia; Insulin receptor; Trichosanthes kirilowii