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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (11): 1264-1269.doi: 10.3736/jcim20111116

• Original Experimental Research • Previous Articles     Next Articles

6-Gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice

Evan Prince Sabina, Samuel Joshua Pragasam, Suresh Kumar, Mahaboobkhan Rasool()   

  1. School of Bio Sciences and Technology, VIT University, Vellore 632014, Tamil Nadu, IndiaSchool of Bio Sciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India
  • Received:2011-07-12 Accepted:2011-09-05 Online:2011-11-20 Published:2011-11-15

Objective: To investigate the hepatoprotective efficacy of 6-gingerol against acetaminophen-induced hepatotoxicity in mice.
Methods: Mice were injected with a single dose of acetaminophen (900 mg/kg) to induce hepatotoxicity, while 6-gingerol (30 mg/kg) or the standard drug silymarin (25 mg/kg) was given 30 min after the acetaminophen administration. The mice were sacrificed 4 h after acetaminophen injection to determine the activities of liver marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin in serum, and lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glutathione) in liver homogenate.
Results: The treatment of 6-gingerol and silymarin to acetaminophen-induced hepatotoxicity showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, and ALP) and total bilirubin in serum (P<0.05). In addition, 6-gingerol and silymarin treatment prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status in the liver of acetaminophen-intoxicated mice (P<0.05).
Conclusion: The results evidently demonstrate that 6-gingerol has promising hepatoprotective effect which is comparable to the standard drug silymarin.

Key words: 6-gingerol, plant extracts, hepatoprotective, antioxidants, lipid peroxidation, mice




LPO (μmol of
TBA reactants
per 100 g tissue)

SOD (U per mg
protein per min)

CAT (μmol of H2O2
consumed per mg
protein per min)

GPx (μg of GSH
utilized per mg
protein per min)

GR (nmol of NADPH oxidized
per mg protein per min)

GST (nmol of CDNB-GSH conjugate
formed per mg protein per min)

Total reduced GSH
(nmol/mg protein)










(900 mg/kg body weight, i.p.)









Acetaminophen plus 6-gingerol
(30 mg/kg body weight, i.p.)









Acetaminophen plus silymarin
(25 mg/kg body weight, i.p.)









(30 mg/kg body weight, i.p.)




157.43± 9.81











Total bilirubin (μmol/L)







(900 mg/kg body weight, i.p.)


3 408.3±169.0*

2 211.7±173.0*



Acetaminophen plus 6-gingerol
(30 mg/kg body weight, i.p.)


1 061.7±82.6




Acetaminophen plus silymarin
(25 mg/kg body weight, i.p.)


1 281.7±51.2




(30 mg/kg body weight, i.p.)


1 003.3±55.4



[1] Ma X, Gang DR . Metabolic profiling of in vitro micro- propagated and conventionally greenhouse grown ginger {Zingiber officinale^). Phytochemistry. 2006; 67(20):2239-2255.
doi: 10.1016/j.phytochem.2006.07.012
[2] Kim JK, Kim Y, Na KM, Surh YJ, Kim TY . [ 6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo . Free Radic Res. 2007 ; 41(5):603-614.
doi: 10.1080/10715760701209896 pmid: 17454143
[3] Young HY, Luo YL, Cheng HY, Hsieh WC, Liao JC, Peng WH . Analgesic and anti-inflammatory activities of [6]-gingerol.[J] Ethnopharmacol. 2005; 96(1-2) : 207-210.
doi: 10.1016/j.jep.2004.09.009 pmid: 15588672
[4] Guh JH, Ko FN, Jong TT, Teng CM . Antiplatelet effect of gingerol isolated from Zingiber officinale.[J] Pharm Pharmacol. 1995; 47(4):329-332.
doi: 10.1111/j.2042-7158.1995.tb05804.x pmid: 7791032
[5] Chang WS, Chang YH, Lu FJ, Chiang HC . Inhibitory effects of phenolics on xanthine oxidase. Anticancer Res. Anticancer Res. 1994; 14(2A) : 501-506.
pmid: 8017853
[6] Kim SO, Chun KS, Kundu JK, Surh YJ . Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-κB and p38 MAPK in mouse skin. Biofactors. 2004; 21(1-4):27-31.
doi: 10.1002/biof.v21:1/4
[7] Wallace JL . Acetaminophen hepatotoxicity : NO to the rescue. Br J Pharmacol. 2004; 143(1) : 1-2.
doi: 10.1038/sj.bjp.0705781 pmid: 15345657
[8] Song Z, McClain CJ, Chen T . S-Adenosylmethionine protects against acetaminophen-induced hepatotoxicity in mice. Pharmacology. 2004; 71(4):199-208.
doi: 10.1016/S0016-5085(03)83654-5 pmid: 15240996
[9] Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N, Mishra PP, Samuel J . Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice.[J] Pharm Pharmacol. 2010 ; 62(5):638-643.
doi: 10.1111/(ISSN)2042-7158
[10] Sener G, Omurtag GZ, Sehirli O, Tozan A, Yiiksel M, Ercan F, Gedik N . Protective effects of Ginkgo biloba against acetaminophen-induced toxicity in mice. Mol Cell Biolchem. 2006; 283(1-2):39-45.
doi: 10.1007/s11010-006-2268-8 pmid: 16444584
[11] Ohkawa H, Ohishi N, Yagi K . Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2) : 351-358.
doi: 10.1016/0003-2697(79)90738-3
[12] Marklund S, Marklund G . Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974; 47(3) : 469-474.
doi: 10.1111/ejb.1974.47.issue-3
[13] Sinha AK . Colorimetric assay of catalase. Anal Biochem. 1972; 47(2) : 389-394.
doi: 10.1016/0003-2697(72)90132-7
[14] Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG . Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973; 179(73) : 588-590.
doi: 10.1111/j.1753-4887.1980.tb05961.x pmid: 4686466
[15] Bellomo G, Mirabelli F, DiMonte D, Richelmi P, Thor H, Orrenius C, Orrenius S . Formation and reduction of glutathione-protein mixed disulfides during oxidative stress : a study with isolated hepatocytes and menadione (2-methyl-l, 4-naphthoquinone) . Biochem Pharmacol. 1987; 36(8) : 1313-1320.
doi: 10.1016/0006-2952(87)90087-6
[16] Habig WH, Pabst MJ, Jakoby WB . Glutathione S- transferases : the first enzymatic step in mercapturic acid formation.[J] Biol Chem. 1974; 249(22):7130-7139.
[17] Moron MS, Depierre JW, Mannervik B. Moron MS, Depierre JW, Mannervik B . Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979 ; 582(1):67-78.
doi: 10.1016/0304-4165(79)90289-7
[18] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ . Protein measurement with the Folin phenol reagent.[J] Biol Chem. 1951; 193(1):265-275.
[19] Sabir SM, Rocha JB . Antioxidant and hepatoprotective activity of aqueous extract of Solatium fastigiatum( false “Jurubeba”)against paracetamol-induced liver damage in mice. J Ethnopharmacol. 2008; 120(2):226-232.
doi: 10.1016/j.jep.2008.08.017
[20] Rasool MK, Sabina EP, Lavanya K, Nithya P . Therapeutic effect of Indian Ayurvedic herbal formulation Triphala on acetaminophen-induced hepatotoxicity in mice. J Pharmacol Toxicol. 2007: 2(8):725-731.
doi: 10.3923/jpt.2007.725.731
[21] Shankar K, Vaidya VS, Apte UM, Manautou JE, Ronis MJ, Bucci TJ, Mehendale HM . Type 1 diabetic mice are protected from acetaminophen hepatotoxicity. Toxicol Sci. 2003; 73(2):220-234.
doi: 10.1093/toxsci/kfg059 pmid: 12700423
[22] Ajith TA, Hema U, Aswathy MS . Zingiber off icinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status. Food Chem Toxicol. 2007; 45(11):2267-2272.
doi: 10.1016/j.fct.2007.06.001
[23] Ippoushi K, Azuma K, Ito H, Horie H, Higashio H . [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite- induced oxidation and nitration reactions. Life Sci. 2003; 73(26) : 3427-3437.
doi: 10.1016/j.lfs.2003.06.022
[24] Lee TY, Lee KC, Chen SY, Chang HH . 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κB pathways in lipopolysaccharide-stimulated mouse macrophages. Biochem Biophys Res Commun. 2009; 382(1) : 134-139.
doi: 10.1016/j.bbrc.2009.02.160
[25] Lee C, Park GH, Kim CY, Jang JH .[ 6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system. Food Chem Toxicol. 2011; 49(6):1261-1269.
doi: 10.1016/j.fct.2011.03.005
[26] Ramadan LA, Roushdy HM, Abu Senna GM, Amin NE, El-Deshw OA . Radioprotective effect of silymarin against radiation induced hepatotoxicity. Pharmacol Res. 2002; 45(6) : 447-454.
doi: 10.1111/j.1742-1241.2006.00972.x pmid: 12162944
[27] Horváth ME, González-Cabello R, Blázovics A, van der Looij M, Barta I, Müzes G, Gergely P, Fehér J . Effect of silibinin and vitamin E on restoration of cellular immune response after partial hepatectomy.[J] Ethnopharmacol. 2001; 77(2-3):227-232.
doi: 10.1016/S0378-8741(01)00298-7
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