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http://dx.doi.org/10.6116/kjh.2020.35.1.45.

Randomized Double-blind Human Trial to Evaluate Efficacy and Safety of Rhus verniciflua Stokes (Lacca Sinica Exsiccata) and Eucommia ulmoides Oliver (Eucommiae Cortex) Extract Combination (ILF-RE) on Improvement of Liver Function  

Youn, Young (Imsil Cheese & Food Research Institute)
Baek, Hyang-Im (Healthcare Claims & Management Incorporation)
Jin, Hee-Yeon (Imsil Cheese & Food Research Institute)
Jeong, Da-Young (Healthcare Claims & Management Incorporation)
Shen, Lei (Dept. of Constitutional Medicine, Wonkwang University Jeonju Korean Medicine Hospital)
Joo, Jong-Cheon (Dept. of Constitutional Medicine, Wonkwang University Jeonju Korean Medicine Hospital)
Park, Soo-Jung (Dept. of Sasang Constitutional Medicine, Woosuk University Korean Medicine Hospital)
Publication Information
The Korea Journal of Herbology / v.35, no.1, 2020 , pp. 45-55 More about this Journal
Abstract
Objectives : The purpose of this study is to determine whether Rhus verniciflua Stokes with Latin name Lacca Sinica Exsiccata, and Eucommia ulmoides Oliver with Latin name Eucommiae Cortex Extract Combination (ILF-RE) improves laboratory test results in participants with liver function disorder. Methods : This study was conducted at Woosuk university Korean medicine hospital where participants with high serum alanine transaminase (ALT) levels from 45 to 135 U/L were enrolled. Subjects received ILF-RE 3.6 g (1.2 g/day as ILF-RE) or placebo 3.6 g for 12 weeks. It was confirmed that urushiol was not detected in ILF-RE. The primary outcomes were the decrement degree of serum ALT and gamma-glutamyl transferase (GGT) levels between two groups. The secondary outcomes were the decrement degree of serum aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LD), total bilirubin, total cholesterol, triglyceride (TG) and fatty liver index (FLI) levels between two groups. Adverse events, skin prick tests, laboratory tests, and vital signs were observed and analyzed to confirm the safety of ILF-RE.1) Results : In the ILF-RE group, the liver function index ALT, GGT, lipid metabolism index TG, and fatty liver index FLI were significantly decreased compared to the placebo group. There was no significant difference in ILF-RE group in terms of adverse events, severe adverse events, skin prick test, laboratory test, and vital signs compared with placebo group. Conclusions : ILF-RE was found to be effective in improving liver function. In addition, no clinically significant adverse events or body changes were observed during this study.
Keywords
Rhus verniciflua Stokes; Qi Shu; Lacca Sinica Exsiccata; Eucommia ulmoides Oliver; Du Zhong; Eucommiae Cortex; ILF-RE; liver function;
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Times Cited By KSCI : 4  (Citation Analysis)
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1 Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-21.   DOI
2 Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413 -9.   DOI
3 Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology. 2005;42(5):987-1000.   DOI
4 Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387-95.   DOI
5 Cha JY, Heo JS, Cho YS. Effect of zinc-enriched yeast FF-10 strain on the alcoholic hepatotoxicity in alcohol feeding rats. Food Sci Biotechnol. 2008;17(6):1207-13.
6 Jeon BS, Park JW, Shin GG, Kim BK, Kim HK, Cho YS, Cha JY. Effect of fermented mushroom milk on hyperlipidemia and hepatic injury in streptozocin-induced diabetic and Zucker fatty rats. Food Sci Biotechnol. 2004;13(5): 576-80.
7 Chang IM. Liver-protective activities of aucubin derived from traditional oriental medicine. Res Commun Mol Pathol Pharmacol. 1998;102(2):189-204.
8 Lee CK, Kim NY, Han YN, Choi JW. Effects of pretreated Korean red ginseng on carbon tetrachloride and galactosamine-induced hepatotoxicity in rats. J Ginseng Res. 2003;27(1):1-10.   DOI
9 Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med. 1989;55(5):417-9.   DOI
10 Muriel P, Garciapina T, Perez-Alvarez V, Mourelle M. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol. 1992;12(6):439-42.   DOI
11 Park SJ, Yang BW, Hahm YT, Oh DH, Kim JB, Yang JY, Kang BS. Antioxidative activities of Rhus verniciflua Bark from different area. Korean J Food Nutr. 2012;25(3):430-5.   DOI
12 Lee SH, Jeong HS, Kang TS. Antimicrobial and Antioxidative Activities of Hot Water Extracts from Heat-Air Drid Rhus verniciflua Stokes. Food Eng Prog. 2013;17(1):1-7.
13 Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363(14):1341-50.   DOI
14 Park SY, Ahn SH, Kim HH. Effects of Fructus Amomi Amari, Eucommiae Cortex, Bombyx Batryticatus Extract on Improving Symptoms of Late-onset Hypogonadism. J Physiol Pathol Korean Med. 2019;33(2):89-101.   DOI
15 Lala V, Minter DA. Liver Function Tests. Source-StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019-.
16 Yun DY, Park SH, Lee JS. Effects of Eucommiae Cortex on Myofiber Type Transition and MyoD Expression in Hind Limb Muscle Atrophy of Rats. J Korean Med Rehabil. 2008;18(1):47-63.
17 Yoon SJ, Kim KY, Kim GY, Nam KW, Sim KC, Kim EJ, Chung HW, Kim HW, Kim GD. Effects of Eucommia Ulmoides Oliver and Treadmill Exercise on the Osteoporosis of Rats Caused by Glucocorticoid Induction. J Physiol Pathol Korean Med. 2008;22(4):884-90.
18 Nutrition and Functional Research Team. National Institute of Food and Drug Safety Evaluation. Health functional food evaluation guide. 'May help liver health'. Nutrition and Functional Research Team. 2015.
19 Keane PM, Garcia L, Gupta RN, Walker WH. Serum gamma glutamyl transpeptidase in liver disorders. Clin Biochem. 1973;6(1):41-5.   DOI
20 Bae MJ, Oh IH, Park JS, Lee SY, Lee JG, Kim YJ, Jung DW, Yi YH, Cho YH, Choi EJ. The Association between Elevated GGT with Alcohol Consumption and with Insulin Resistance. J Obes Metab Syndr. 2011;20(3):113-20.
21 Choi HS, Kim MK, Park HS, Yun SE, Mun SP, Kim JS, Sapkota K, Kim S, Kim TY, Kim SJ. Biological detoxification of lacquer tree (Rhus verniciflua Stokes) stem bark by mushroom species. Food Sci Biotechnol. 2007;16(6):935-42.
22 Park HJ, Kwon SH, Kim GT, Lee KT, Choi JH, Choi JW, Park KY. Physicochemical and biological characteristics of flavonoids isolated from the heartwoods of Rhus verniciflua. Korean J Pharmacogn. 2000;3(3):345-50.
23 Kim HY, Woo KS, Hwang IG, Lee YR, Jeong HS. Effects of Heat Treatments on the Antioxidant Activities of Fruits and Vegetables. Korean Soc Food Sci Technol. 2008;40(2):166-70.
24 Lee MS, Kim JS, Cho SM, Lee SO, Kim SH, Lee HJ. Fermented Rhus verniciflua Stokes Extract Exerts an Antihepatic Lipogenic Effect in Oleic-Acid-Induced HepG2 Cells via Upregulation of AMPActivated Protein Kinase. J Agric Food Chem. 2015;63(32):7270-6.   DOI
25 Turkmen N, Sari F, Velioglu YS. The effects of cooking methods total phenolics and antioxidant activity of selected green vegetables. Food Chem. 2005;93(4):713-8.   DOI
26 Yoo GJ, Kim SY, Choi AR, Son MH, Kim DC, Chae HJ. Effect of Rhus verniciflua Stokes Extract on the Alcohol-Metabolizing Enzyme Activities. KSBB J. 2009;24(1):101-5.
27 Ahn EM, Park SJ, Choi WC, Choi SH, Baek NI. Antioxidant Activity of Isolated Compounds from the Heartwoods of Rhus verniciflua. Appl Biol Chem. 2007;50(4):358-61.
28 Choi KC, Chung WT, Kwon JK, Jang YS, Yu JY, Park SM, Lee JC. Chemoprevention of a flavonoid fraction from Rhus verniciflua Stokes on aflatoxin B1-induced hepatic damage in mice. J Appl Toxicol. 2011;31(2):150-6.   DOI
29 Gil MN, Choi DR, Yu KS, Jeong JH, Bak DH, Kim DK, Lee NS, Lee JH, Jeong YG, Na CS, Na DS, Ryu KH, Han SY. Rhus verniciflua Stokes attenuates cholestatic liver cirrhosis-induced interstitial fibrosis via Smad3 down-regulation and Smad7 up-regulation. Anat Cell Biol. 2016;49(3):189-98.   DOI
30 Ko JH, Lee SJ, Lim KT. Rhus verniciflua Stokes glycoprotein (36kDa) has protective activity on carbon tetrachloride-induced liver injury in mice. Environ Toxicol Pharmacol. 2006 ;22(1):8-14.   DOI
31 Lee HY, Lee GH, Lee MR, Kim HK, Kim NY, Kim SH, Lee YC, Kim HR, Chae HJ. Eucommia ulmoides Oliver Extract, Aucubin, and Geniposide Enhance Lysosomal Activity to Regulate ER Stress and Hepatic Lipid Accumulation. PLoS One. 2013;8(12):e81349.   DOI
32 Bianco A, Iavarone C, Trogolo C. Structure of eucommiol, a new cyclopentenoid-tetrol from Eucommia ulmoides. Tetrahedron. 1974;30(23-24):4117-21.   DOI
33 Luo D, Or TCT, Yang CLH, Lau A. Antiinflammatory activity of iridoid and catechol derivatives from Eucommia ulmoides Oliver. ACS Chem Neurosci. 2014;5(9):855-66.   DOI
34 Fu GM, Tong HY, Zeng HL, Zou B, Chai JX, Zhang LN, Xie MY, Chen F, Wan Y. Antioxidant and xanthine oxidase inhibitory activity of Eucommia ulmoides Oliver leaf extracts. Pak J Pharm Sci. 2018;31(4): 1333-9.
35 Li J, Liang XL, Zhou BX, Chen XW, Xie PF, Jiang HM, Jiang ZH, Yang ZF, Pan XP. (h)-pinoresinol-O-b-D-glucopyranoside from Eucommia ulmoides Oliver and its anti-inflammatory and antiviral effects against influenza A (H1N1) virus infection. Mol Med Rep. 2019;19(1):563-72.
36 Jeon JR, Park JR. Effect of Eucommia ulmoides Leaf Water Extract on Hepatotoxicity of Carbon Tetrachloride-Induced Rats. J Korean Soc Food Sci Nutr. 2002;31(1): 124-30.   DOI
37 Jin CF, Li B, Lin SM, Yadav RK, Kim HR, Chae HJ. Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE) in the CCl4 -Induced Acute Liver Lipid Accumulation in Rats. Int J Endocrinol. 2013; 2013:751854.   DOI
38 Lee HY. Lee GH, Yoon Y, Chae HJ. Rhus verniciflua and Eucommia ulmoides Protects Against High-Fat Diet-Induced Hepatic Steatosis by Enhancing Anti-Oxidation and AMPK Activation. Am J Chin Med. 2019;47(6):1253-70.   DOI
39 Zheng J, Yan Q, Zhang K, Zheng Y, Zhao S. Protective effects of different extracts of Eucommia ulmoides Oliv. against thioacetamide-induced hepatotoxicity in mice. Indian J Exp Biol. 2012;50(12):875-82.
40 Food Safety Nara. Food.Safety-Information by Function. What is liver health. [cited 2020 Dec 1]. Available from : URL : https://www.foodsafetykor ea.go.kr/portal/healthyfoodlife/functionality View13.do?menu_grp=MENU_NEW01&menu_no=2657
41 Lee HY, Yoon Y, Chae HJ. The effects of herbal extracts on CCl4-induced ROS accumulation and cell death in hepatocytes. Orient Pharm Expl Med. 2018;18(3):257-64.   DOI
42 Lee HY, Lee GH, Yoon Y, Chae HJ. R. verniciflua and E. ulmoides Extract (ILF-RE) Protects against Chronic CCl4-Induced Liver Damage by Enhancing Antioxidation. Nutrients. 2019;11(2):382.   DOI