Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses

Biomed Pharmacother. 2017 Nov:95:520-528. doi: 10.1016/j.biopha.2017.08.115. Epub 2017 Sep 5.

Abstract

Aims: The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF).

Materials and methods: The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN).

Results: Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner.

Conclusions: EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways.

Keywords: Chronic renal failure; Erhuang Formula; Fibrosis; Inflammation.

MeSH terms

  • Adenine
  • Animals
  • Blood Urea Nitrogen
  • Chromatography, High Pressure Liquid
  • Creatinine / blood
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • Inflammation / complications*
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Kidney / pathology*
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / pathology
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Drugs, Chinese Herbal
  • Erhuang formula
  • RNA, Messenger
  • Creatinine
  • Adenine