title: Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats.
abstract: OBJECTIVE
  Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl4 to a greater degree in diabetic animals.
  
  
  METHODS
  ELISA and Western Blot analysis were used to examine PAR2 signaling pathway in diabetic CCl4-rats and non-diabetic CCl4-rats.
  
  
  RESULTS
  AGS inhibited the protein expression of PAR2 and its downstream pathway PKA and PKCɛ in CCl4-rats. Notably, the effects of AGS were greater in CCl4-rats with diabetes. AGS also significantly attenuated the CCl4-induced upregulations of pro-inflammatory cytokines, namely interleukin-1β, interleukin-6 and tumor necrosis factor-α accompanied with decreases of collagenic parameters such as hexadecenoic acid, laminin and hydroxyproline. Additionally, AGS improved the CCl4-induced exaggerations of liver index and functions including alanine aminotransferase, aspartate aminotransferase. Moreover, TGF-β1, a marker of hepatic fibrosis, was increased in CCl4-rats and AGS inhibited increases in TGF-β1 induced by CCl4.
  
  
  CONCLUSIONS
  AGS alleviates hepatic fibrosis by inhibiting PAR2 signaling expression and its effects are largely enhanced in diabetic animals. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of hepatic fibrosis; and results of our study are likely to shed light on strategies for application of AGS because it has potentially greater therapeutic effectiveness for hepatic fibrosis in diabetes.
authors.forename: Zhenchang
authors.initials: Z
authors.lastname: Wang
authors.forename: Quanqiang
authors.initials: Q
authors.lastname: Li
authors.forename: Mingpeng
authors.initials: M
authors.lastname: Xiang
authors.forename: Fengying
authors.initials: F
authors.lastname: Zhang
authors.forename: Dongyu
authors.initials: D
authors.lastname: Wei
authors.forename: Zhixi
authors.initials: Z
authors.lastname: Wen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D044464:Receptor, PAR-2; D012503:Saponins; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C052064:astragaloside A; D013311:Streptozocin; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017868:Cyclic AMP-Dependent Protein Kinases; D051744:Protein Kinase C-epsilon
keywords: Astragaloside; Diabetes; Hepatic fibrosis; PAK; PAR2; PKC