NMED-01과 NMED-02의 간기능 개선에 대한 인체 효능 평가 = A Randomized, Double-blind, Placebo-controlled Study to the efficacy and Safety of NMED-01 and NMED-02 in Mild Alcoholic Liver Subjects

다국어 초록 (Multilingual Abstract)

Objectives: The purpose of this study was to determine whether NMED-01 or NMED-02 improves laboratory test results in participants with liver function disorder. Methods : This is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at Semyung university oriental medicine hospital in Jecheon where participants with high level of serum γ-GTP (60-350 U/L) were enrolled. The intervention consisted of three times daily ingestion of either two capsules of placebo, NMED-01 (NeuMed. co. ltd., Seoul), or NMED-02 (NeuMed. co. ltd., Seoul) for twelve weeks. To evaluate the efficacy and safety of NMED-01 and NMED-02, we primarily evaluated the degree of decrement of serum γ-GPT level among three groups. Secondarily the decrement of serum ALT, AST, and triglyceride level in each group were also evaluated. Adverse effects were monitored during the twelve weeks treatment. Results : The change of γ-GTP level of NMED-01 group was lower than that of placebo group at the end of 12-week administration (28.1±38.7 U/L vs. 9.3±27.0 U/L, p=0.046). Other variables including AST, ALT, and triglyceride level were not significantly reduced. The decrement of γ-GPT, AST, ALT, and triglyceride level of NMED-02 group was not significant. There were no significant adverse effects or toxicities during treatment period. Conclusions : Participants receiving NMED-01 had improvement in laboratory test results. Despite a modest sample size, our results suggest that NMED-01 are safe and may be potentially effective in improving liver function. However, NMED-02 have lack of a detectable effect in this study.

참고문헌 (Reference)

1 김진현, "헛개나무로부터 생리활성물질의 추출 및 효능에 관한 연구" 한국생물공학회 21 (21): 11-15, 2006

2 동미숙, "헛개나무(Hovenia dulcis var. koreana) 과병 열수추출분획물의 간보호 및 혈중 알콜 저하 작용" 대한약학회 48 (48): 34-40, 2004

3 이응준, "최근 2년간 발생한 급성 A형간염의 임상 특성에 관한 연구" 대한소화기학회 52 (52): 298-303, 2008

4 이현화, "자초(Lithospermum erythrorhizon)추출물의 투여가 Galactosamine으로 유도된 간손상에 미치는 보호 효과" 한국현미경학회 40 (40): 29-35, 2010

5 변정현, "알코올 상담 센터 환자를 대상으로 한 알코올 의존의 생물학적 표지자 연구" 대한생물정신의학회 13 (13): 269-274, 2006

6 김영식, "알코올 및 사염화탄소에 의해 유발된 급만성 간손상에 대한 지구자 열수추출물의 보호효과" 대한본초학회 28 (28): 25-32, 2013

7 채희복, "알코올 간질환" 대한소화기학회 53 (53): 275-282, 2009

8 유양희, "세포 및 동물모델에서의 알코올에 의해 유발된 간손상에 대한 지구자 추출물의 보호효과" 한국식품영양과학회 38 (38): 154-159, 2009

9 최정국, "산화동물 모델 흰쥐 간세포에 대한 枳椇子와 枳椇枝의 항산화 효과 연구" 대한본초학회 24 (24): 129-138, 2009

10 김종호, "랫드 일차 배양 간세포에서 에탄올의 독성에 대한 헛개나무 물추출물의 보호효과" 대한약학회 52 (52): 56-61, 2008

11 안병수, "당뇨병 유발 흰쥐에서 헛개나무 추출물의 항산화 효과" 한국임상수의학회 27 (27): 366-373, 2010

12 Selinger MJ, "γ-Glutamyl transpeptidase activity in liver disease: serum elevation is independent of hepatic GGTP activity" 125 (125): 283-290, 1982

13 Lee HJ, "Update and Perspectives on alcoholic liver disease in Korea 2010" 16 (16): 23-44, 2010

14 Fang H, "Treatment of chronic liver injuries in mice by oral administration of ethanolic extract of the fruit of Hovenia dulcis" 35 (35): 693-703, 2007

15 Han SH, "The effects of Puerariae radix catechins administration on liver function in carbon tetrachloride-treated rats" 24 (24): 713-720, 1995

16 Lee CH, "The effects of Puerariae Radix catechins administration on liver function in carbon tetrachloride-treated rats" 24 (24): 713-719, 1995

17 Korea Food & Drug Administration(KFDA), "The Korean Herbal Pharmacopoeia"

18 Woo HJ, "Studies on the effects of Puerariae radix and Artemisiae herba on experimental liver damages induced by alcohol, d-galactosamine and CCl4" 18 (18): 411-429, 1997

19 Kurihara T, "Studies on the constituents of flowers V. on the components of Pueria thunbergiana Benth (2). Isolation of new isoflavones glcosides" 95 : 1283-1285, 1975

20 Hong YL, "Studies on the biological activities of the extracts from Hovenia dulcis Thunb" 11 : 1-11, 2000

21 Huh LH, "Studies on anti-inflammatory activity and its mechanism of daidzein" 31 (31): 154-163, 1987

22 Chang-Hun Park, "Structure-Activity Relationships of Components from the Roots of Pueraria thunbergiana Having Aldose Reductase Inhibitory and Antioxidative Activity" 대한화학회 28 (28): 493-495, 2007

23 Jeong CH, "Some Functional Properties of extracts from leaf and fruit stalk of Hovenia dulcis" 7 (7): 291-296, 2000

24 Hawke RL, "Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C" 50 (50): 434-449, 2010

25 Gjerde H, "Serum Gamma‐glutamyltransferase: an epidemiological indicator of alcohol consumption?" 82 (82): 1027-1031, 1987

26 Du J, "Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice" 48 (48): 953-958, 2010

27 Yates WR, "Risk factors for alcohol hepatotoxicity among male alcoholics" 20 (20): 155-162, 1987

28 Chen X, "Puerarin improves metabolic function leading to hepatoprotective effects in chronic alcohol-induced liver injury in rats" 20 (20): 849-852, 2013

29 Kim OK, "Protective effects of extracts of Hovenia dulcis Thunb on hepatotoxicity in carbon tetrachloride intoxicated rats" 30 (30): 1260-1265, 2001

30 Yong Pil Hwang, "Protective Effects of Puerarin on Carbon Tetrachloride-Induced Hepatotoxicity" 대한약학회 30 (30): 1309-1317, 2007

31 Zeng GY, "Pharmacologic studies on Puerariae Radix :effects of puerariae flavones on coronary circulation, cardiac hemodynamics and myocardial metabolism in dogs" 95 (95): 145-150, 1982

32 Zhu H, "Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence" 13 (13): 133-142, 2012

33 Arao T, "Oleanenetype triterpene glycosides from Pueraria radix. IV. six new saponins from Pueraria Lobata" 45 : 362-366, 1997

34 Sato T, "Mechanism of antioxidant action of pueria glycoside(PG)-I (an isoflavonoid) and mangiferin (axanthonoid)" 40 : 721-724, 1992

35 Keung WM, "Kudzu root an ancient chinese source of modern antisotropic agents" 47 : 499-506, 1998

36 Cho JY, "Isolation and identification of 3-Methoxy-4-hydroxybenzoic Acid and 3-Methoxy-4-hydroxycinnamic acid from hot water extracts of Hovenia dulcis Thunb and confirmation of their antioxidative and antimicrobial activity" 32 (32): 1403-1408, 2000

37 Lin RC, "Isoflavone compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism" 20 (20): 659-663, 1996

38 Lee HC, "Influence of Protaetia brevitarsis extract on liver damage induced by carbon tetrachloride and ethanol in rats" 11 (11): 405-414, 2001

39 Subramanian S, "Hypertriglyceridemia secondary to obesity and diabetes" 1821 (1821): 819-825, 2012

40 Textbook Compilation Committee of college of Korean Medicine, "Herbology" Younglim 734-, 1991

41 Kim HC, "Herbal Pharmocology" Jipmoon 2001

42 Hase K, "Hepatoprotective effect of Hovenia dulcis THUNB. on experimental liver injuries induced by carbon tetrachloride or D-galactosamine/lipopolysaccharide" 20 (20): 381-385, 1997

43 배미진, "Gamma-glutamyltransferase 상승과 알코올 섭취, 인슐린 저항성과의 연관성" 대한비만학회 20 (20): 113-120, 2011

44 Pessione F, "Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence" 23 (23): 45-53, 2003

45 Barouki R, "Ethanol effects in a rat hepatoma cell line: Induction of γ‐Glutamytransferase" 3 (3): 323-329, 1983

46 Lee JS, "Effects of extracts of Pueraria radix on lipid peroxidation in ethanol-administered rats" 28 (28): 901-906, 1999

47 Ji Y, "Effects of Hovenia dulcis Thunb on blood sugar and hepatic glycogen in diabetic mice" 25 (25): 190-191, 2002

48 Ma JY, "Effect of Hovenia dulcis on liver protection in SD male rats treated with CCl4" 12 (12): 103-109, 2006

49 Choi K, "Diagnostic usefulness of serum γ-glutamyl transferase(GGT) activity in fatty liver and relationship with other factors" 57 : 1006-1013, 1999

50 Sohail U, "Diagnosis and management of alcoholic hepatitis" 16 (16): 717-736, 2012

51 Tuma J, "Dangerous byproducts of alcohol breakdown-focus on adducts" 27 (27): 285-290, 2003

52 Xie CI, "Daidzin apotent selective inhibitor of human mitochondrial aldehyde dehydrogenase" 90 : 1247-1250, 1993

53 An SW, "Comparison of hepatic detoxification activity and reducing serum alcohol concentration of Hovenia dulcis THUNB and Alnus japonica Steud" 7 (7): 263-268, 1999

54 Jun M, "Comparison of antioxidant activities of isoflavones from kudzu root (Pueraria lobata Ohwi)" 68 : 2117-2122, 2003

55 Persson J, "Comparison between different methods of detecting patients with excessive consumption of alcohol" 223 (223): 101-109, 1988

56 Byun KS, "Clinical and pathologic spectrum of alcoholic liver diseases" 3 (3): 307-315, 1997

57 김홍태, "Carbon Tetrachloride로 유발된 Rat의 간장과 신장 손상시 헛개나무 추출액의 치료효과" 한국임상수의학회 28 (28): 20-27, 2011

58 현동환, "CCI4로 유발된 백서의 간손상에 대한 갈근의간보호작용 연구" 대한동의병리학회 17 (17): 297-307, 2003

59 Lee MK, "Biological activities of Hovenia dulcis THUNB" 7 (7): 185-192, 1999

60 Keung WM, "Biochemical studies of a new class of alcohol dehydrogenase inhibition from Pueriae Radix" 17 : 1254-1260, 1993

61 Yoshikawa M, "Bioactive saponins and glycosides. IV. Four methyl-migrated 16, 17-seco-dammarane triterpene glycosides from Chinese natural medicine, hoveniae semen seu fructus, the seeds and fruit of Hovena dulcis THUNB.: Absolute stereostructures and inhibitory activity on histamine release of hovenidulciosides A1, A2, B1, and B2" 44 (44): 1736-1743, 1996

62 Yoshikawa M, "Bioactive constituents of Chinese natural medicines. III. Absolute stereostructures of new dihydroflavonols, hovenitins I, II, and III" 117 (117): 108-118, 1997

63 Oh MJ, "Antioxidative components of Pueraria root" 22 (22): 792-793, 1990

64 Weicheng Hu, "Antioxidant Activities of Various Extracts of Hovenia dulcis Thunb Fruits" 한국자원식물학회 23 (23): 207-213, 2010

65 Friedman SL, "Acetaldehyde and alcoholic fibrogenesis: fuel to the fire, but not the spark" 12 (12): 609-612, 1990

66 Szasz G, "A kinetic photometric method for serum γ-glutamyl transpeptidase" 15 (15): 124-136, 1969