Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-ß and Smad3 expression on unilateral ureteral obstruction rat model

Phytomedicine. 2016 Apr 15;23(4):331-9. doi: 10.1016/j.phymed.2016.01.013. Epub 2016 Feb 11.

Abstract

Background: Renal interstitial fibrosis is characterized by excessive accumulation of extracellular matrix, which leads to end-stage renal failure.

Purpose: 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).

Study design: 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.

Conclusion: 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.

Keywords: Chronic kidney diseases; Elsholtzia ciliata (Thunb.) Hylander; Interstitial fibrosis; Transforming growth factor-β; Unilateral ureteral obstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Fibrosis / drug therapy
  • Fibrosis / etiology
  • Fibrosis / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Lamiaceae / chemistry*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Mice
  • Nephritis / drug therapy
  • Nephritis / etiology
  • Nephritis / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / drug therapy*

Substances

  • Cytokines
  • Plant Extracts
  • Polyphenols
  • Smad3 Protein
  • Smad3 protein, rat
  • Transforming Growth Factor beta
  • Matrix Metalloproteinase 9