Skip to main content
Top
Published in: European Journal of Nutrition 1/2013

Open Access 01-02-2013 | Original Contribution

Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model

Authors: Jia Xiao, Yick Pang Ching, Emily C. Liong, Amin A. Nanji, Man Lung Fung, George L. Tipoe

Published in: European Journal of Nutrition | Issue 1/2013

Login to get access

Abstract

Purpose

To investigate the hepato-protective properties and underlying mechanisms of SAMC in a non-alcoholic fatty liver disease (NAFLD) rat model.

Methods

Female rats were fed with a diet comprising highly unsaturated fat diet (30% fish oil) for 8 weeks to develop NAFLD with or without an intraperitoneal injection of 200 mg/kg SAMC three times per week. After euthanasia, blood and liver samples of rats were collected for histological and biochemical analyses.

Results

Co-treatment of SAMC attenuated NAFLD-induced liver injury, fat accumulation, collagen formation and free fatty acids (FFAs). At the molecular level, SAMC decreased the lipogenesis marker and restored the lipolysis marker. SAMC also reduced the expression levels of pro-fibrogenic factors and diminished liver oxidative stress partly through the inhibition in the activity of cytochrome P450 2E1-dependent pathway. NAFLD-induced inflammation was also partially mitigated by SAMC treatment via reduction in the pro-inflammatory mediators, chemokines and suppressor of cytokine signaling. The protective effect of SAMC is also shown partly through the restoration of altered phosphorylation status of FFAs-dependent MAP kinase pathways and diminished in the nuclear transcription factors (NF-κB and AP-1) activity during NAFLD development.

Conclusions

SAMC is a novel hepato-protective agent against NAFLD caused by abnormal liver functions. Garlic or garlic derivatives could be considered as a potent food supplement in the prevention of fatty liver disease.
Appendix
Available only for authorised users
Literature
1.
go back to reference Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ (2001) Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 21:17–26CrossRef Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ (2001) Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 21:17–26CrossRef
2.
go back to reference Loguercio C, De Simone T, D’Auria MV, de Sio I, Federico A, Tuccillo C, Abbatecola AM, Del Vecchio Blanco C, Agostinacchio E, Benedetti A, Svegliati-Baroni G, Budillon G, Cimino L, Chiaramonte M, Saltarelli P, Fraioli F, Fargion S, Fracanzani AL, Floreani A, Blasone L, Grieco A, Miele L, Rappaccini G, Gasbarrini G, Loria P, Carulli N, Marchesini G, Bianchi G, Matarazzo M, Mecenate F, Persico M, De Marino F, Portincasa P, Palmieri V, Palasciano G, Spadaro A, Ajello A, Smedile A, Bugianesi E, Visconti M, Salvio A, Varriale M, Vecchione R, Terracciano LM, Guido M (2004) Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. Digest Liver Dis 36:398–405 Loguercio C, De Simone T, D’Auria MV, de Sio I, Federico A, Tuccillo C, Abbatecola AM, Del Vecchio Blanco C, Agostinacchio E, Benedetti A, Svegliati-Baroni G, Budillon G, Cimino L, Chiaramonte M, Saltarelli P, Fraioli F, Fargion S, Fracanzani AL, Floreani A, Blasone L, Grieco A, Miele L, Rappaccini G, Gasbarrini G, Loria P, Carulli N, Marchesini G, Bianchi G, Matarazzo M, Mecenate F, Persico M, De Marino F, Portincasa P, Palmieri V, Palasciano G, Spadaro A, Ajello A, Smedile A, Bugianesi E, Visconti M, Salvio A, Varriale M, Vecchione R, Terracciano LM, Guido M (2004) Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. Digest Liver Dis 36:398–405
4.
go back to reference Polyzos SA, Kountouras J, Zavos C (2009) Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 9:299–314CrossRef Polyzos SA, Kountouras J, Zavos C (2009) Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 9:299–314CrossRef
5.
go back to reference Ban JO, Yuk DY, Woo KS, Kim TM, Lee US, Jeong HS, Kim DJ, Chung YB, Hwang BY, Oh KW, Hong JT (2007) Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. J Pharmacol Sci 104:374–383CrossRef Ban JO, Yuk DY, Woo KS, Kim TM, Lee US, Jeong HS, Kim DJ, Chung YB, Hwang BY, Oh KW, Hong JT (2007) Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. J Pharmacol Sci 104:374–383CrossRef
6.
go back to reference Lee Y (2008) Induction of apoptosis by S-allylmercapto-l-cysteine, a biotransformed garlic derivative, on a human gastric cancer cell line. Int J Mol Med 21:765–770 Lee Y (2008) Induction of apoptosis by S-allylmercapto-l-cysteine, a biotransformed garlic derivative, on a human gastric cancer cell line. Int J Mol Med 21:765–770
7.
go back to reference Xiao D, Pinto JT, Soh JW, Deguchi A, Gundersen GG, Palazzo AF, Yoon JT, Shirin H, Weinstein IB (2003) Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal kinase 1 activation. Cancer Res 63:6825–6837 Xiao D, Pinto JT, Soh JW, Deguchi A, Gundersen GG, Palazzo AF, Yoon JT, Shirin H, Weinstein IB (2003) Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal kinase 1 activation. Cancer Res 63:6825–6837
8.
go back to reference Pedraza-Chaverri J, Barrera D, Maldonado PD, Chirino YI, Macias-Ruvalcaba NA, Medina-Campos ON, Castro L, Salcedo MI, Hernandez-Pando R (2004) S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo. BMC Clin Pharmacol 4:5. doi:10.1186/1472-6904-4-5 CrossRef Pedraza-Chaverri J, Barrera D, Maldonado PD, Chirino YI, Macias-Ruvalcaba NA, Medina-Campos ON, Castro L, Salcedo MI, Hernandez-Pando R (2004) S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo. BMC Clin Pharmacol 4:5. doi:10.​1186/​1472-6904-4-5 CrossRef
9.
go back to reference Sumioka I, Matsura T, Yamada K (2001) Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice. Eur J Pharmacol 433:177–185CrossRef Sumioka I, Matsura T, Yamada K (2001) Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice. Eur J Pharmacol 433:177–185CrossRef
11.
go back to reference XIao J, Liong EC, Ling MT, Ching YP, Fung ML, Tipoe GL (2011) S-allylmercaptocysteine reduces carbon tetrachloride induced hepatic oxidative stress and necroinflammmation via nuclear factor kappa B-dependent pathways in mice. Eur J Nutr. doi:10.1007/s00394-011-0217-0 XIao J, Liong EC, Ling MT, Ching YP, Fung ML, Tipoe GL (2011) S-allylmercaptocysteine reduces carbon tetrachloride induced hepatic oxidative stress and necroinflammmation via nuclear factor kappa B-dependent pathways in mice. Eur J Nutr. doi:10.​1007/​s00394-011-0217-0
12.
go back to reference Tipoe GL, Ho CT, Liong EC, Leung TM, Lau TY, Fung ML, Nanji AA (2009) Voluntary oral feeding of rats not requiring a very high fat diet is a clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD). Histol Histopathol 24:1161–1169 Tipoe GL, Ho CT, Liong EC, Leung TM, Lau TY, Fung ML, Nanji AA (2009) Voluntary oral feeding of rats not requiring a very high fat diet is a clinically relevant animal model of non-alcoholic fatty liver disease (NAFLD). Histol Histopathol 24:1161–1169
14.
go back to reference Sumioka I, Matsura T, Kasuga S, Itakura Y, Yamada K (1998) Mechanisms of protection by S-allylmercaptocysteine against acetaminophen-induced liver injury in mice. Jpn J Pharmacol 78:199–207CrossRef Sumioka I, Matsura T, Kasuga S, Itakura Y, Yamada K (1998) Mechanisms of protection by S-allylmercaptocysteine against acetaminophen-induced liver injury in mice. Jpn J Pharmacol 78:199–207CrossRef
15.
go back to reference 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 (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321CrossRef 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 (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321CrossRef
16.
go back to reference Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622. doi:10.1373/clinchem.2008.112797 CrossRef Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622. doi:10.​1373/​clinchem.​2008.​112797 CrossRef
19.
go back to reference Melo AM, Bittencourt P, Nakutis FS, Silva AP, Cursino J, Santos GA, Ashino NG, Velloso LA, Torsoni AS, Torsoni MA (2011) Solidago chilensis Meyen hydroalcoholic extract reduces JNK/IkappaB pathway activation and ameliorates insulin resistance in diet-induced obesity mice. Exp Biol Med (Maywood). doi:10.1258/ebm.2011.011105 Melo AM, Bittencourt P, Nakutis FS, Silva AP, Cursino J, Santos GA, Ashino NG, Velloso LA, Torsoni AS, Torsoni MA (2011) Solidago chilensis Meyen hydroalcoholic extract reduces JNK/IkappaB pathway activation and ameliorates insulin resistance in diet-induced obesity mice. Exp Biol Med (Maywood). doi:10.​1258/​ebm.​2011.​011105
20.
go back to reference Schattenberg JM, Galle PR (2010) Animal models of non-alcoholic steatohepatitis: of mice and man. Digest Dis 28:247–254CrossRef Schattenberg JM, Galle PR (2010) Animal models of non-alcoholic steatohepatitis: of mice and man. Digest Dis 28:247–254CrossRef
21.
go back to reference Lam TK, Yoshii H, Haber CA, Bogdanovic E, Lam L, Fantus IG, Giacca A (2002) Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta. Am J Physiol Endocrinol Metab 283:E682–E691. doi:10.1152/ajpendo.00038.2002 Lam TK, Yoshii H, Haber CA, Bogdanovic E, Lam L, Fantus IG, Giacca A (2002) Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta. Am J Physiol Endocrinol Metab 283:E682–E691. doi:10.​1152/​ajpendo.​00038.​2002
23.
go back to reference Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM (2005) JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 280:35361–35371. doi:10.1074/jbc.M504611200 CrossRef Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM (2005) JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 280:35361–35371. doi:10.​1074/​jbc.​M504611200 CrossRef
24.
go back to reference Ghanim H, Aljada A, Daoud N, Deopurkar R, Chaudhuri A, Dandona P (2007) Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Diabetologia 50:278–285. doi:10.1007/s00125-006-0508-9 CrossRef Ghanim H, Aljada A, Daoud N, Deopurkar R, Chaudhuri A, Dandona P (2007) Role of inflammatory mediators in the suppression of insulin receptor phosphorylation in circulating mononuclear cells of obese subjects. Diabetologia 50:278–285. doi:10.​1007/​s00125-006-0508-9 CrossRef
25.
go back to reference Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12 Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12
27.
29.
go back to reference Wang XL, Zhang L, Youker K, Zhang MX, Wang J, LeMaire SA, Coselli JS, Shen YH (2006) Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase. Diabetes 55:2301–2310. doi:10.2337/db05-1574 CrossRef Wang XL, Zhang L, Youker K, Zhang MX, Wang J, LeMaire SA, Coselli JS, Shen YH (2006) Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase. Diabetes 55:2301–2310. doi:10.​2337/​db05-1574 CrossRef
30.
go back to reference Fujishiro M, Gotoh Y, Katagiri H, Sakoda H, Ogihara T, Anai M, Onishi Y, Ono H, Abe M, Shojima N, Fukushima Y, Kikuchi M, Oka Y, Asano T (2003) Three mitogen-activated protein kinases inhibit insulin signaling by different mechanisms in 3T3-L1 adipocytes. Mol Endocrinol 17:487–497. doi:10.1210/me.2002-0131 CrossRef Fujishiro M, Gotoh Y, Katagiri H, Sakoda H, Ogihara T, Anai M, Onishi Y, Ono H, Abe M, Shojima N, Fukushima Y, Kikuchi M, Oka Y, Asano T (2003) Three mitogen-activated protein kinases inhibit insulin signaling by different mechanisms in 3T3-L1 adipocytes. Mol Endocrinol 17:487–497. doi:10.​1210/​me.​2002-0131 CrossRef
31.
go back to reference Liu HY, Collins QF, Xiong Y, Moukdar F, Lupo EG Jr, Liu Z, Cao W (2007) Prolonged treatment of primary hepatocytes with oleate induces insulin resistance through p38 mitogen-activated protein kinase. J Biol Chem 282:14205–14212. doi:10.1074/jbc.M609701200 CrossRef Liu HY, Collins QF, Xiong Y, Moukdar F, Lupo EG Jr, Liu Z, Cao W (2007) Prolonged treatment of primary hepatocytes with oleate induces insulin resistance through p38 mitogen-activated protein kinase. J Biol Chem 282:14205–14212. doi:10.​1074/​jbc.​M609701200 CrossRef
32.
go back to reference Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336. doi:10.1038/nature01137 CrossRef Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336. doi:10.​1038/​nature01137 CrossRef
33.
go back to reference Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, Czaja MJ (2006) JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 43:163–172. doi:10.1002/hep.20999 CrossRef Schattenberg JM, Singh R, Wang Y, Lefkowitch JH, Rigoli RM, Scherer PE, Czaja MJ (2006) JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology 43:163–172. doi:10.​1002/​hep.​20999 CrossRef
34.
go back to reference Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A (2006) A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 169:846–860CrossRef Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A (2006) A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 169:846–860CrossRef
35.
go back to reference Wang Z, Yao T, Song Z (2010) Extracellular signal-regulated kinases 1/2 suppression aggravates transforming growth factor-beta1 hepatotoxicity: a potential mechanism for liver injury in methionine-choline deficient-diet-fed mice. Exp Biol Med (Maywood) 235:1347–1355. doi:10.1258/ebm.2010.010160 CrossRef Wang Z, Yao T, Song Z (2010) Extracellular signal-regulated kinases 1/2 suppression aggravates transforming growth factor-beta1 hepatotoxicity: a potential mechanism for liver injury in methionine-choline deficient-diet-fed mice. Exp Biol Med (Maywood) 235:1347–1355. doi:10.​1258/​ebm.​2010.​010160 CrossRef
37.
go back to reference Mebratu Y, Tesfaigzi Y (2009) How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle 8:1168–1175CrossRef Mebratu Y, Tesfaigzi Y (2009) How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle 8:1168–1175CrossRef
39.
go back to reference Tanaka S, Haruma K, Yoshihara M, Kajiyama G, Kira K, Amagase H, Chayama K (2006) Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J Nutr 136:821S–826S Tanaka S, Haruma K, Yoshihara M, Kajiyama G, Kira K, Amagase H, Chayama K (2006) Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J Nutr 136:821S–826S
Metadata
Title
Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model
Authors
Jia Xiao
Yick Pang Ching
Emily C. Liong
Amin A. Nanji
Man Lung Fung
George L. Tipoe
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
European Journal of Nutrition / Issue 1/2013
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0301-0

Other articles of this Issue 1/2013

European Journal of Nutrition 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.