title: Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy.
abstract: OBJECTIVE
  The combination of Chinese herbs, Astragali Radix and Angelicae Sinensis Radix, could alleviate renal interstitial fibrosis. Astragaloside IV (AS-IV) and ferulic acid (FA) are the two major active constituents in this combination. In this study, we employed rats with unilateral ureteral obstruction to determine whether AS-IV and FA have the same renoprotective effects and investigated the mechanisms of this action.
  
  
  METHODS
  Renal pathological changes were evaluated after treatment with AS-IV, FA or AS-IV + FA (AF) for 10 days. Meanwhile, the expression of transforming growth factor β(1) (TGF-β(1) ), fibronectin, α-smooth muscle actin (α-SMA), phosphorylation of c-Jun NH(2) -terminal kinase (p-JNK) and nitric oxide (NO) production in kidney were determined. The expressions of fibronectin, α-SMA, mitogen-activated protein kinases [JNK, extracellular signal-regulated kinases (ERK), P38] in TGF-β(1) -treated NRK-49F cells or interleukin-1-treated HK-2 cells after AS-IV, FA or AF were assessed.
  
  
  RESULTS
  AF alleviated the infiltration of mononuclear cells, tubular atrophy and interstitial fibrosis; reduced the expression of fibronectin, α-SMA, TGF-β(1) and p-JNK; and dramatically increased the production of NO in obstructed kidneys. Neither AS-IV nor FA alone improved renal damage, but both increased NO production. AF inhibited α-SMA and fibronectin expression in NRK-49F or HK-2 cells. Furthermore, AF significantly inhibited IL-1β-induced JNK phosphorylation, without affecting ERK or P38 phosphorylation. Neither AS-IV nor FA alone had any effect on the cells.
  
  
  CONCLUSIONS
  AS-IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial-mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: L Q
authors.initials: LQ
authors.lastname: Meng
authors.forename: J W
authors.initials: JW
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J R
authors.initials: JR
authors.lastname: Zhao
authors.forename: M Y
authors.initials: MY
authors.lastname: Shang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: S Y
authors.initials: SY
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Qu
authors.forename: S Q
authors.initials: SQ
authors.lastname: Cai
authors.forename: X M
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D008297:Male; D009395:Nephritis, Interstitial / Q000209:etiology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000150:complications*
chemical_list: D003373:Coumaric Acids; D012503:Saponins; D014315:Triterpenes; D009569:Nitric Oxide; C052064:astragaloside A; C004999:ferulic acid