Dahuang Fuzi Decoction ameliorates tubular epithelial apoptosis and renal damage via inhibiting TGF-β1-JNK signaling pathway activation in vivo.

Abstract:

ETHNOPHARMACOLOGICAL RELEVANCE: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. MATERIALS AND 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). CONCLUSION:DFD alleviated adenine-induced tubular epithelial apoptosis and renal damage in vivo, presumably through the suppression of TGF-β1-JNK pathway activation.

journal_name

J Ethnopharmacol

authors

Tu Y,Sun W,Wan YG,Gao K,Liu H,Yu BY,Hu H,Huang YR

doi

10.1016/j.jep.2014.08.035

subject

Has Abstract

pub_date

2014-10-28 00:00:00

pages

115-24

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(14)00629-1

journal_volume

156

pub_type

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