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KMID : 1149220180260030207
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Korean Journal of Oriental Medical Prescription
2018 Volume.26 No. 3 p.207 ~ p.221
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Study of hepatoprotective effect of Haegan-jeon through activation of nuclear factor erythroid 2-related factor 2 and optimization of herbal composition based on molecular mechanism
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Kim Jae-Kwang
Jung Ji-Yun
Park Sang-Mi
Park Chung-A
Ku Sae-Kwang
Byun Sung-Hee
Cho Il-Je
Kim Sang-Chan
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Abstract
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Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE.
Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, 10 μM) and iron (5 μM) for inducing oxidative stress. Cell viability, GSH contents, H2O2 production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on CCl4-induced liver injury mice model.
Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, H2O2 production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in CCl4-induced liver injury mice model, HE-op had an ability to ameliorate CCl4-mediated increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE.
Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.
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KEYWORD
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Haegan-jeon, Optimization of herbal composition, Oxidative stress, Nuclear factor erythroid 2-related factor 2 (Nrf2), Hepatoprotection
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