title: Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach.
abstract: OBJECTIVE
  Xiao-Ke-An (XKA) is a traditional Chinese medicine (TCM) formula for the treatment of type 2 diabetes (T2D), and the effective ingredients and their targets as well as the mechanisms of XKA remain to be elucidated. In this study we investigated the therapeutic mechanisms of XKA in the treatment of T2D in mice using a Fangjiomics approach.
  
  
  METHODS
  KKAy mice feeding on a high-fat diet were used as models of T2D, and were orally treated with XKA (0.75 or 1.5 g · kg(-1) · d(-1)) for 32 d. Microarray mRNA expression data were obtained from the livers of the mice. Differentially expressed genes (DEGs) were identified by reverse rate analysis and ANOVA analysis. The compounds in XKA were identified by LC-MS analysis or collected from TCM databases. The relationships between the compounds and targets were established by combining the DEGs with information derived from mining literature or herb target databases. Relevant pathways were identified through a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using WebGestalt.
  
  
  RESULTS
  The compound-target-pathway network based on compounds identified by LC-MS analysis (NCA) included 20 constituent compounds, 46 targets and 36 T2D-related pathways, whereas the compound-target-pathway network based on compounds collected from databases (NCD) consisted of 40 compounds, 68 targets and 21 pathways. In the treatment of T2D, XKA might act mainly by improving carbohydrate and lipid metabolism, as well as ameliorating insulin resistance, inflammation and diabetic vascular complications.
  
  
  CONCLUSIONS
  The network-based approach reveals complex therapeutic mechanisms of XKA in the treatment of T2D in mice that involve numerous compounds, targets, and signaling pathways.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Zhen-zhong
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yi-yu
authors.initials: YY
authors.lastname: Cheng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002853:Chromatography, Liquid; D016000:Cluster Analysis; D057225:Data Mining; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008516:Medicine, Chinese Traditional / Q000379:methods*; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D049490:Systems Biology / Q000379:methods*; D018511:Systems Integration; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; C000605226:Xiao-Ke-An