Browse > Article
http://dx.doi.org/10.14374/HFS.2021.29.4.277

Effect of Bojungikgi-tang on cytochrome P450 and LKB1-AMPK anti-oxidant signaling pathway  

Song, Yu Rim (School of Korean Medicine, Dongguk University)
Park, Sun-Dong (School of Korean Medicine, Dongguk University)
Kim, Young Woo (School of Korean Medicine, Dongguk University)
Publication Information
Herbal Formula Science / v.29, no.4, 2021 , pp. 277-283 More about this Journal
Abstract
Objectives : We investigated the effects of Bojungikgi-tang (BJIGT) on P450 cytochrome enzyme and oxidative stress in the cells. Methods : We enrolled the HepG2 hepatocyte cell line to assess MTT assay, flow cytometer, and immunoblotting analysis. Expression of CYP450 was confirmed by immunoblotting analysis in the Huh7 cell line. Results : We determined that BJIKT markdely changed the expression of the CYP2C19, CYP2D6, and CYP2E1. Moreover, BJIKT inhibited the cell toxicity induced by arachidonic acid + iron treatment, as assessed by FACS analysis. BJIKT induced AMPK activation, which increased the phophorylation of ACC. Conclusions : This study verified the effects of BJIKT, on P450, ROS production, mitochondrial damage and AMPK signaling pathway, which might give us the scientific information about the traditional herbal prescription.
Keywords
Bojungikgi-tang; AMPK; LKB1; CYP450;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Li AP. Preclinical in vitro screening assays for drug-like properties. Drug Discovery Today: Technologies. 2005;2(2):179-185.
2 Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers and inhibitors. Drug Metabolism Reviews. 1997;29:413-580.   DOI
3 Park YC, Kim J, Lee S. Mechanisms and Prevention for Metabolism and Toxicity of Korean Herbal-Medicine. Korean journal of oriental preventive medical society. 2008;12(1):73-87.
4 Akram M, Iquebal MA, Naimuddin K, Sahi J, Grepper S, Smith C. Hepatocytes as a Tool in Drug Metabolism, Transport and Safety Evaluations in Drug Discovery. Current Drug Discovery Technologies. 2010;7(3):188-198.   DOI
5 Choi JM, Jeon JS, Kim SK. The Optimization of Method for Prediction of Drug-Induced Liver Injury Using HepG2 Cells Cultured with Human Liver Microsomes. Yakhak Hoeji. 2015;59(5):201-206.
6 Lee J, Ahn SH. Recent Trends in Drug Interaction Studies based on Drug Metabolism. Yakhak Hoeji. 2020;64(1):8-20.   DOI
7 Tang L, Ye L, Lv C, Zheng Z, Gong Y, Liu Z. Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes. Toxicology Letters. 2011;202(1):47-54.   DOI
8 Thanan R, Oikawa S, Hiraku Y, Ohnishi S, Ma N, Pinlaor S, Yongvanit P, Kawanishi S, Murata M. Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer. Int J Molecul Sci. 2014;16(1):193-217.   DOI
9 Balboa MA, Balsinde J. Oxidative stress and arachidonic acid mobilization. Biochim Biophys Acta. 2006;1761(4): 385-391.   DOI
10 Neufeld, E.J. Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: new data, new questions. Blood 2006;107(9):3436-3441.   DOI
11 Seo HL, Baek SY, Lee EH, Lee JH, LEE SG, Kim KY, et al., Liqustri lucidi Fructus inhibits hepatic injury and functions as an antioxidant by activation of AMP-activated protein kinase in vivo and in vitro. Chemico-Biological Interactions. 2017;262:57-68.   DOI
12 Kim JK, Park SM, Jegal KH, Kim YW, Byun SH, Kim SC, et al., Gleditsia Spina Extract Protects Hepatocytes from Oxidative Stress through Nrf2 Activation. The Korea Journal of Herbology. 2015;30(4):57-64.   DOI
13 Lee EH, Baek SY, Kim KY, Lee SG, Kim SC, Lee HS, et al., Effect of Rheum undulatum Linne extract and Glycyrriza uralensis Fischer extract against arachidonic acid and iron-induced oxidative stress in HepG2 cell and CCl4-induced liver injury in mice. Herbal Formula Science. 2016;24(3): 163-174.   DOI
14 Ha J, Lee S. Role of AMPK in the Regulation of Cellular Energy Metabolism. Journal of Korean Endocrine Society. 2010;25(1):9-17.   DOI
15 Chen JK, Capdevila J, Harris RC. Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Mol cell Biol. 2001;21(18): 6322-31.   DOI
16 Lim HS, Kim YJ, Sohn E, Yoon J, Kim BY, Jeong SJ. Bojungikgi-Tang, a Traditional Herbal Formula, Exerts Neuroprotective Effects and Ameliorates Memory Impairments in Alzheimer's Disease-Like Experimental Models. Nutrients. 2018;10(12):1952   DOI
17 Cai M, Lee SH, Yang EJ. Bojungikgi-tang Improves Muscle and Spinal Cord Function in an Amyotrophic Lateral Sclerosis Model. Mol Neurobiol. 2019;56:2394-2407   DOI
18 Galaris, D., Pantopoulous, K. Oxidative stress and iron homeostasis: mechanistic and health aspects. Crti Rev Clin Lab Sci. 2008;45(1):1-23.   DOI
19 Alexander A, Walker CL. The role of LKB1 and AMPK in cellular responses to stress and damage. FEBS Letters. 2011;585(7):952-957.   DOI
20 Son JW, Jung JY, Kim KY, Hwangbo M, Park CA, Cho IJ, et al., The Protective Activity of Soeumin Bojungykgi-tang Water Extract Against Oxidative Stress-induced Hepato-Toxicity. Herbal Formula Science, 2017;25(4):509-52616.   DOI
21 Ko HL, Jegal KH, Song SY, Kim NE, Kang J, Byun SH, et al., Water Extract of Rosa laevigata Michx. Protects Hepatocytes from Arachidonic Acid and Iron-mediated Oxidative Stress. The Korea Journal of Herbology. 2015;30(6):7-15.   DOI
22 Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121-135.   DOI
23 Jung EH, Kim SC, Cho IJ, Kim YW. Akebiae Caulis Inhibits Oxidative Stress through AMPK Activation. Korean Journal of Oriental Physiology & Pathology. Korean Society of Oriental Pathology. 2015;29(1):18-26.   DOI
24 Galaris D, Pantopoulos K. Oxidative stress and iron homeostasis: mechanistic and health aspects. Critical Reviews in Clinical Laboratory Sciences. 2008;45(1):1-23.   DOI
25 Gomez-Lechon MJ, Donato MT, Castell JV, Jover R. Human hepatocytes in primary culture: The choice to investigate drug metabolism in man. Current Drug Metabolism, 2004;5:443-462.   DOI
26 Jin SE, Ha H, Shin HK. Effects of Herbal Formulas Bojungikgi-tang and Palmijihwang-hwan on Inflammation in RAW 264.7 Cells and the Activities of Drug-Metabolizing Enzymes in Human Hepatic Microsomes. Journal of Medicinal Food. 2018;21(11):1173-1187   DOI
27 Suh Jk, Jeon IS. Basic Understanding of Iron Metabolism. Clin Pediatr Hematol Oncol. 2018; 25:1-9.   DOI
28 Asha A, Vidyavathi. Role of Human Liver Microsomes in In Vitro Metabolism of Drugs-A Review. Appl Biochem Biotechnol. 2010;160:1699-1722.   DOI
29 Brandon EFA, Raap CD, Meijerman I, Beijnen JH, Schellens JHM. An update on in vitro test methods in human hepatic drug biotransformation research: Pros and cons. Toxicology and Applied Pharmacology. 2003;189(3):233-246.   DOI