title: Activation of AQP4, p66Shc and endoplasmic reticulum stress is involved in inflammation by carrageenan and is suppressed by argirein, a derivative of rhein.
abstract: OBJECTIVE
  We investigated the effect of argirein on acute inflammation edema and examined that aquaporin 4 (AQP4), p66Shc and activating transcription factor (ATF-6) might be involved in carrageenan-induced rat paw inflammation and be reversed by argirein, rhein and indometacin, but not L-arginine.
  
  
  METHODS
  Inflammation was produced by carrageenan injected into rat paw and treated orally with argirein (100 mg/kg), rhein (100 mg/kg), L-arginine (100 mg/kg) or indometacin (5 mg/kg). Inflammatory oedema and biomarkers were examined.
  
  
  RESULTS
  Swelling was reduced by argirein, rhein and indometacin; argirein was more effective than rhein at 1 h following medication. Activation of AQP4, p66Shc, ATF-6, NADPH oxidase subunits p22phox, gp91phox and matrix metalloproteinase 2 (P < 0.01) was significant and was suppressed by arginine, rhein and indometacin but not by l-arginine.
  
  
  CONCLUSIONS
  Activated AQP4, endoplasmic reticulum stress and p66Shc were actively implicated in the inflammation and these were suppressed by argirein, and its activity is favorable due to synergism in combination with L-arginine.
authors: Zhejiang Chinese Medical University, Hangzhou             China Pharmaceutical University, Research Division of Pharmacology, Nanjing, China.
authors: Xiao-Dong
authors: XD
authors: Cong
authors: You
authors: Y
authors: Wu
authors: De-Zai
authors: DZ
authors: Dai
authors: Ming-Jian
authors: MJ
authors: Ding
authors: Yun
authors: Y
authors: Zhang
authors: Yin
authors: Y
authors: Dai
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D051401:Aquaporin 4 / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002351:Carrageenan; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D051702:Activating Transcription Factor 6; D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D051401:Aquaporin 4; C497113:Atf6 protein, rat; D015415:Biomarkers; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C576350:argirein; D002351:Carrageenan; D001120:Arginine; D019255:NADPH Oxidases; D020778:Matrix Metalloproteinase 2; D007213:Indomethacin; C020491:rhein