Wen-pi-tang-Hab-Wu-ling-san attenuates kidney fibrosis induced by ischemia/reperfusion in mice.
Renal fibrosis is highly implicated as a cause of chronic renal failure, for which suitable therapeutics have not yet been developed. Recently, it was reported that Wen-pi-tang-Hab-Wu-ling-san (WHW) extract attenuates epithelial cells undergoing mesenchymal transition in cultured Madin-Darby canine kidney cells. This study investigated whether WHW extract prevents renal fibrosis induced by ischemia/reperfusion (I/R) in mice. Ischemia/reperfusion resulted in kidney fibrosis at 14 days after the procedure. When WHW was administered orally to mice beginning from 2 days after the onset of ischemia until killing, the fibrosis was significantly reduced. WHW administration significantly prevented a post-ischemic decrease of copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activities, leading to decreased lipid peroxidation and hydrogen peroxide production. In addition, WHW administration attenuated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) and attenuated the activation of nuclear factor-kappa B (NF-kappaB) in the kidneys subjected to ischemia. In conclusion, WHW extract attenuated the renal fibrosis and the attenuation was associated with a reduction of oxidative stress and an inhibition of ERK1/2, JNK1/2, p38 and NF-kappaB activation. WHW extract may be an attractive agent to attenuate the progression of fibrosis.
Seok
Young Mi
YM
Department of Anatomy, Kyungpook National University School of Medicine, 101 Dongin2ga, Junggu, Daegu, 700-422, South Korea.
Kim
Jinu
J
Park
Mae Ja
MJ
Boo
Yong Chool
YC
Park
Yong-Ki
YK
Park
Kwon Moo
KM
D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8