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Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway

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Abstract

Objective

To investigate the cytoprotective effects of Saeng-kankunbi-tang (生肝健脾汤, 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.

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Authors and Affiliations

  1. Department of Internal Oriental Medicine of Hepatology, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea

    In Woo Lee & Hong Sik Choi

  2. Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu, 38610, Korea

    Hee Yoon Choi, Ju-Hee Lee, Seung Mo Kim, Sae Kwang Ku, Sang Chan Kim & Young Woo Kim

  3. College of Oriental Medicine, Dongguk University, Gyeongju, 38066, Korea

    Ju-Hee Lee & Sun-Dong Park

  4. School of Mental Health, Jining Medical University, Jining, Shandong Province, 272067, China

    Rong-jie Zhao  (赵容杰)

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  1. In Woo Lee
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  2. Hee Yoon Choi
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Correspondence to Young Woo Kim or Hong Sik Choi.

Additional information

Supported by the National Research Foundation of Korea Grant funded by the Korea government (No. 2014R1A2A2A01007375, No. 2012R1A5A2A42671316)

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Lee, I.W., Choi, H.Y., Lee, JH. et al. Saeng-Kankunbi-Tang (生肝健脾汤) protects liver against oxidative damage through activation of ERK/Nrf2 pathway. Chin. J. Integr. Med. 22, 619–628 (2016). https://doi.org/10.1007/s11655-016-2466-5

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  • DOI: https://doi.org/10.1007/s11655-016-2466-5

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