Kushenol C Prevents Tert-Butyl Hydroperoxide and Acetaminophen-Induced Liver Injury |
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Authors: | Byoung Ok Cho Jang Hoon Kim Denis Nchang Che Hyun Ju Kang Jae Young Shin Suping Hao Ji Hyeon Park Feng Wang Yun Ji Lee Seon Il Jang |
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Institution: | 1.Research Institute, Ato Q&A Co., LTD, Jeonju-si 55069, Korea; (H.J.K.); (J.Y.S.);2.Institute of Health Science, Jeonju University, Jeonju-si 55069, Korea;3.Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA, Eumsung 27709, Korea; (J.H.K.); (Y.J.L.);4.Department of Health Management, Jeonju University, Jeonju-si 55069, Korea; (S.H.); (J.H.P.); (F.W.) |
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Abstract: | Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC’s activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress. |
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Keywords: | kushenol C Nrf2 Akt antioxidant OGG1 liver injury |
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