title: Dahuang Fuzi Decoction ameliorates tubular epithelial apoptosis and renal damage via inhibiting TGF-β1-JNK signaling pathway activation in vivo.
abstract: BACKGROUND
  Dahuang Fuzi Decoction (DFD) is a traditional well-prescribed formula for the treatment of chronic kidney disease (CKD) in China. This study was carried out to examine the effects of DFD in adenine-induced tubular epithelial apoptosis and renal damage, in comparison with allopurinol (AP), then to clarify the therapeutic mechanisms in vivo.
  
  
  METHODS
  A rat model of renal damage was created by adenine. Rats in Normal and Vehicle groups received distilled water, while rats in DFD and AP groups received DFD and AP, respectively. Proteinuria; urinary N-acetyl-β-D-glucosaminidase (NAG) levels; the blood biochemical parameters; renal histopathology damage; transferase-mediated dUTP nick-end labeling (TUNEL)-staining; the key molecular protein expressions in mitochondrial and transforming growth factor (TGF)-β1-c-JunNH2-terminal kinase (JNK) pathways were examined, respectively.
  
  
  RESULTS
  Adenine administration induced severe renal damages, as indicated by the mass proteinuria, the heavy urinary NAG, and the marked histopathological injury in tubules and interstitium. This was associated with the activation of TGF-β1-JNK signaling pathway and tubular epithelial apoptosis. DFD treatment, however, significantly prevented proteinuria and urinary NAG elevation, and attenuated tubular epithelial apoptosis. It suppressed the protein expressions of Bax and cleaved caspase-3, whereas it enhanced the protein expression of Bcl-2. Furthermore, it also suppressed the protein levels of TGF-β1 as well as phosphorylated-JNK (p-JNK).
  
  
  CONCLUSIONS
  DFD alleviated adenine-induced tubular epithelial apoptosis and renal damage in vivo, presumably through the suppression of TGF-β1-JNK pathway activation.
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China; Department of Graduate School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: 381968515@qq.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Wan
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Kun
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Graduate School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Graduate School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Bing-Yin
authors.initials: BY
authors.lastname: Yu
authors.affiliation: Department of Graduate School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Graduate School, Nanjing University of Chinese Medicine, Nanjng, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Huang
mesh_terms: D000118:Acetylglucosaminidase; D058186:Acute Kidney Injury / Q000188:drug therapy*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts; D051381:Rats; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1 / Q000187:drug effects*
chemical_list: D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C575009:fuzi drug herbal; D000493:Allopurinol; D000118:Acetylglucosaminidase
keywords: (-) – asarinin (PubChem CID: 11869417); Adenine-induced renal failure; Dahuang Fuzi Decoction; Transforming growth factor-β1; Tubular epithelial apoptosis; aloe-emodin (PubChem CID: 10207); c-JunNH2-terminal kinase; chrysophanol (PubChem CID: 10208); emodin (PubChem CID: 3220); emodin-3-methyl ether (PubChem CID: 10639); rhein (PubChem CID: 10168)