title: AMPK synergizes with the combined treatment of 1'-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities.
abstract: METHODS
  Phase II enzymes play important roles in detoxifying xenobiotics. We previously reported that both 1'-acetoxychavicol acetate (ACA) and sodium butyrate individually increased phase II enzyme activities. Here, we determined the combined action of ACA and sodium butyrate on phase II enzyme activities in intestinal epithelial cells (IEC 6).
  
  
  RESULTS
  ACA and sodium butyrate synergistically increased phase II enzyme activities. Protein levels of intranuclear transcription factor NF-E2-related factor 2 (Nrf2) were increased by ACA or sodium butyrate treatment, but treatment with both did not produce a synergistic effect. Intranuclear p53 protein levels were increased by ACA but decreased by sodium butyrate alone or combined treatment with ACA and sodium butyrate. In contrast, p53 acetylation was promoted by sodium butyrate and the ACA and sodium butyrate combination. Inhibition of AMPK activity decreased phase II enzyme activities that were upregulated by treatment with ACA plus sodium butyrate or other phytochemicals, including kaempferol, quercetin, and epigallocatechin-3-gallate. Combined treatment with ACA and sodium butyrate increased phosphorylated AMPK levels.
  
  
  CONCLUSIONS
  These results suggest that ACA and sodium butyrate synergistically contribute to xenobiotics metabolism. The combined ACA and sodium butyrate treatment synergistically upregulated phase II enzyme activities through AMPK activation and p53 acetylation.
authors.affiliation: Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yaku
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui-Yuasa
authors.forename: Yotaro
authors.initials: Y
authors.lastname: Konishi
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima-Yuasa
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives; D002478:Cells, Cultured; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D050217:Metabolic Detoxication, Phase II; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D001592:Benzyl Alcohols; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D015262:Xenobiotics; D020148:Butyric Acid; D002392:Catechin; C045651:epigallocatechin gallate; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D055372:AMP-Activated Protein Kinases; C047948:1'-acetoxychavicol acetate
keywords: 1’-Acetoxychavicol acetate; AMP-activated protein kinase; Dietary fiber; Phase II enzyme; Rat intestine epithelial cells