Wen-pi-tang-Hab-Wu-ling-san reduces ureteral obstructive renal fibrosis by the reduction of oxidative stress, inflammation, and TGF-beta/Smad2/3 signaling.

Abstract

Kidney fibrosis results in chronic renal disease. The current treatment of chronic renal diseases is limited to angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Recently, we found that Wen-pi-tang-Hab-Wu-ling-san (WHW) extract, which has been used to treat renal diseases in herbal medicine for a long time, plays anti-fibrogenic. Here, we investigated the role of WHW in the kidney fibrosis induced by unilateral ureteral obstruction (UUO) in mice. C57BL/6 male mice were subjected to UUO on day 0 and then administered with either WHW (2, 10, or 50 mg/kg of body weight) or vehicle orally from 1 day after UUO to finish the experiment. WHW-administration significantly mitigated the UUO-induced kidney fibrotic changes including tubular atrophy and dilatation, collagen accumulation, expansion of interstitial space and leukocyte infiltration. WHW prevented the increases of oxidative stress by the prevention of UUO-induced decreases of catalase, copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), resulting in reduced production of oxidative stress. Furthermore, WHW reduced transforming growth factor-beta (TGF-beta) expression and phosphorylation of Smad2/3 stimulated by UUO. In conclusion, WHW prevented kidney fibrosis following UUO by the inhibition of inflammation, oxidative stress and TGF-beta/Smad2/3 signaling pathway.

• Authors: Kyong-Jin Jung, Jinu Kim, Yong-Ki Park, Young-Ran Yoon, Kwon Moo Park
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 48 Issue 2 Pg. 522-9 (Feb 2010) ISSN: 1873-6351 [Electronic] England
• PMID: 19913069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Drugs, Chinese Herbal
• Smad2 Protein
• Smad2 protein, mouse
• Smad3 Protein
• Smad3 protein, mouse
• Thiobarbituric Acid Reactive Substances
• Transforming Growth Factor beta
• Oxidoreductases

Topics

• Animals
• Antioxidants (pharmacology)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology)
• Fibrosis (drug therapy, metabolism, pathology)
• Kidney (drug effects, metabolism, pathology)
• Lipid Peroxidation (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (drug effects)
• Oxidoreductases (metabolism)
• Signal Transduction (drug effects)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Transforming Growth Factor beta (metabolism)
• Ureter (drug effects, metabolism)
• Ureteral Obstruction (drug therapy, metabolism, pathology)