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

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 chromatographyphotodiode 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-beta(TGF-beta), 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-kappa B, tumor necrosis factor (TNF-alpha), and interleukin-6 and improved oxidative stress in RAW 264.7 cells. Furthermore, ECE treatment suppressed TGF-beta-induced a-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-alpha, TGF-beta, and Smad 3 were inhibited by ECE treatment. Conclusion: Taken together, the effects of ECE may be mediated by blocking the activation of TGF-beta 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. (C) 2016 Elsevier GmbH. All rights reserved.