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.
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.
Jung
Kyong-Jin
KJ
Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Kim
Jinu
J
Park
Yong-Ki
YK
Yoon
Young-Ran
YR
Park
Kwon Moo
KM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D017392:Thiobarbituric Acid Reactive Substances; D016212:Transforming Growth Factor beta; D010088:Oxidoreductases