Saeng-Kankunbi-Tang () protects liver against oxidative damage through activation of ERK/Nrf2 pathway.
OBJECTIVE
To investigate the cytoprotective effects of Saeng-kankunbi-tang (, SKT), a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum, and its underlying mechanism involved.


METHODS
In mice, blood biochemistry and histopathology were assessed in carbon tetrachloride (CCl4)-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control, CCl4, SKT 500 mg/(kg day) CCl4+SKT 200 or 500 mg/(kg day). In HepG2 cell, tert-butyl hydroperoxide (tBHP) induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, flfluorescence activated cell sorting analysis and western blotting.


RESULTS
The administration of SKT prevented liver damage induced by CCl4 in mice, by inhibition of hepatocyte degeneration and inflflammatory cell infifiltration as well as plasma parameters such as alanine aminotransferase (P<0.01). Moreover, treatment with tBHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However, SKT pretreatment (30-300 μg/mL) reduced this cell death and oxidative stress (P<0.01). More importantly, SKT inhibited the ability of tBHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123 P<0.01). Furthermore, treatment with SKT induced extracellular signal-regulated kinases-mediated nuclear factor erythroid-2-related factor 2 (Nrf2) activation as well as the expressions of heme oxygenase 1 and glutamate- cystein ligase catalytic, Nrf2 target genes.


CONCLUSIONS
SKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.
Department of Internal Oriental Medicine of Hepatology, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.
In Woo
IW
Lee
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.
Hee Yoon
HY
Choi
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.|College of Oriental Medicine, Dongguk University, Gyeongju, 38066, Korea.
Ju-Hee
JH
Lee
College of Oriental Medicine, Dongguk University, Gyeongju, 38066, Korea.
Sun-Dong
SD
Park
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.
Seung Mo
SM
Kim
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.
Sae Kwang
SK
Ku
School of Mental Health, Jining Medical University, Jining, Shandong Province, 272067, China.
Rong-Jie
RJ
Zhao
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea.
Sang Chan
SC
Kim
Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea. ywkim@dhu.ac.kr.
Young Woo
YW
Kim
Department of Internal Oriental Medicine of Hepatology, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea. cheldu@unitel.co.kr.
Hong Sik
HS
Choi
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002251:Carbon Tetrachloride; D016923:Cell Death / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010545:Peroxides; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D010545:Peroxides; D020011:Protective Agents; D017382:Reactive Oxygen Species; C000614299:saeng-kankunbi-tang; D002251:Carbon Tetrachloride; D048049:Extracellular Signal-Regulated MAP Kinases; C000602361:tert-butyl peroxide
aeng-kankunbi-tang; liver; mitochondria; mouse; nuclear factor erythroid-2-related factor 2; oxidative stress