Tacrine, an Oral Acetylcholinesterase Inhibitor, Induced Hepatic Oxidative Damage, Which Was Blocked by Liquiritigenin through GSK3-beta Inhibition
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- Park Sang Mi
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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- Ki Sung Hwan
- College of Pharmacy, Chosun University
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- Han Nu Ri
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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- Cho Il Je
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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- Ku Sae Kwang
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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- Kim Sang Chan
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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- Zhao Rong Jie
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University Department of Pharmacology, Mudanjiang Medical University
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- Kim Young Woo
- Medical Research Center for Globalization of Herbal Formulation, College of Korean Medicine, Daegu Haany University
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抄録
Although the cholinesterase inhibitor tacrine has been successfully used for the treatment of Alzheimer’s disease, it is known to have hepatotoxic effects. Liquiritigenin (LQ), an active flavonoid in Glycyrrhizae radix, exerts protective effects against liver damage. This study investigated the toxic effect of tacrine on hepatocytes and the beneficial effect of LQ on tacrine intoxication in vivo and in vitro, and the underlying mechanism involved. In hepatocyte cell lines, tacrine induced cell death and oxidative stress, as indicated by decreases in cell viability and glutathione (GSH) contents, which were blocked by pretreatment with LQ. Fluorescent activated cell sorter (FACS) analysis revealed that LQ inhibited cellular H2O2 production and mitochondrial dysfunction induced by tacrine in HepG2 cells. Furthermore, LQ promoted inhibitory phosphorylation of glycogen synthase kinase-3β (GSK3β) and prevented decreases in GSK3β phosphorylation induced by tacrine. In rats treatment with tacrine at 30 mg/kg increased hepatic damage as assessed by blood biochemistry and histopathology. Administration of LQ (10 or 30 mg/kg/d, per os (p.o.)) or the hepatoprotective drug sylimarin (100 mg/kg/d) for 3 d inhibited elevations in alanine aminotransferase, aspartate aminotransferase, and histological changes induced by tacrine. These results show that LQ efficaciously protects the rat liver against tacrine-induced liver damage, and suggest that LQ is a therapeutic candidate for ameliorating the hepatotoxic effects of tacrine.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 38 (2), 184-192, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633081984
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- NII論文ID
- 130004872247
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 026069696
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- PubMed
- 25747977
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可