title: Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-ß and Smad3 expression on unilateral ureteral obstruction rat model.
abstract: BACKGROUND
  Renal interstitial fibrosis is characterized by excessive accumulation of extracellular matrix, which leads to end-stage renal failure.
  
  
  OBJECTIVE
  The aim of this study was to explore the effect of Elsholtzia ciliata (Thunb.) Hylander ethanol extract (ECE) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO).
  
  
  METHODS
  After quantitative analysis of ECE using the high performance liquid chromatography-photodiode array (HPLC-PDA) method, an in vitro study was performed to assess the anti-inflammatory and anti-fibrotic effects of ECE, using lipopolysaccharide (LPS) and transforming growth factor-ß (TGF-ß), respectively.
  
  
  METHODS
  For in vivo study, all male Sprague Dawley (SD) rats (n=10/group), except for those in the control group, underwent UUO. The rats were orally treated with water (control), captopril (positive control, 200 mg/kg), and ECE (300 and 500 mg/kg) for 14 days.
  
  
  RESULTS
  In ECE, luteolin and rosmarinic acid were relatively abundant among the other flavonoids and phenolic acids. ECE treatment ameliorated LPS-induced overexpression of nuclear factor-κB, tumor necrosis factor (TNF-α), and interleukin-6 and improved oxidative stress in RAW 264.7 cells. Furthermore, ECE treatment suppressed TGF-ß-induced α-smooth muscle actin and matrix metalloproteinase 9 expression in human renal mesangial cells. In the UUO model, 14 consecutive days of ECE treatment improved UUO-induced renal damage and attenuated histopathological alterations and interstitial fibrosis. Moreover, the renal expression of TNF-α, TGF-ß, and Smad 3 were inhibited by ECE treatment.
  
  
  CONCLUSIONS
  Taken together, the effects of ECE may be mediated by blocking the activation of TGF-ß and inflammatory cytokines, leading subsequently to degradation of the ECM accumulation pathway. Based on these findings, ECE might serve as an improved treatment strategy for renal fibrotic disease.
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Hyun-Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Se-Ra
authors.initials: SR
authors.lastname: Park
authors.affiliation: Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 305-764, Republic of Korea. Electronic address: jyjung@cnu.ac.kr.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009393:Nephritis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy*
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D059808:Polyphenols; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D016212:Transforming Growth Factor beta; D020780:Matrix Metalloproteinase 9
keywords: Chronic kidney diseases; Elsholtzia ciliata (Thunb.) Hylander; Interstitial fibrosis; Transforming growth factor-β; Unilateral ureteral obstruction