Search JIM Advanced Search

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

"


Group

n

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)

Control

6

0.62±0.10

180.83±7.19

160.67±7.26

85.16±3.97

45.14±6.47

83.16±6.18

36.83±5.56

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

6

1.95±0.28*

105.33±6.06*

79.28±6.73*

45.50±3.73*

19.71±3.90*

47.50±10.4*

19.00±3.58*

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

6

0.94±0.14

161.50±9.40

147.17±9.28

74.00±3.35

32.71±7.83

64.00±5.10

24.50±3.27

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

6

0.97±0.12

156.67±9.83

131.00±7.38

68.33±6.02

34.00±5.45

56.83±5.46

29.33±4.13

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

6

0.66±0.11

174.50±12.20

157.43± 9.81

79.33±10.10

42.57±4.89

76.83±5.56

38.16±5.12

"


Group

n

ALT (U/L)

AST (U/L)

ALP (U/L)

Total bilirubin (μmol/L)

Control

6

896.0±65.6

423.3±51.3

173.3±14.4

0.41±1.73

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

6

3 408.3±169.0*

2 211.7±173.0*

464.3±34.7*

0.83±1.89*

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

6

1 061.7±82.6

591.6±57.4

239.8±17.1

0.49±2.43

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

6

1 281.7±51.2

725.7±52.9

242.4±18.6

0.43±1.19

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

6

1 003.3±55.4

536.6±53.5

201.3±12.5

0.43±1.07
[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
[1] Syed Fairus, Hwee Ming Cheng, Kalyana Sundram. Antioxidant status following postprandial challenge of two different doses of tocopherols and tocotrienols. Journal of Integrative Medicine, 2020, 18(1): 68-79.
[2] Yi Ran Hu, San Li Xing, Chuan Chen, Ding Zhu Shen, Jiu Lin Chen. Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. Journal of Integrative Medicine, 2019, 17(6): 404-409.
[3] Stefania Lamponi, Anna Maria Aloisi, Claudia Bonechi, Marco Consumi, Alessandro Donati, Gemma Leone, Claudio Rossi, Gabriella Tamasi, Luana Ghiandai, Ersilia Ferrini, Paolo Fiorenzani, Ilaria Ceccarelli, Agnese Magnani. Evaluation of in vitro cell and blood compatibility and in vivo analgesic activity of plant-derived dietary supplements. Journal of Integrative Medicine, 2019, 17(3): 213-220.
[4] Fatma Mohamed Hussein Shediwah, Khalid Mohammed Naji, Hussein Saleh Gumaih, Fatima A Alhadi, Amani Lutf Al-Hammami, Myrene Roselyn D'Souza. Antioxidant and antihyperlipidemic activity of Costus speciosus against atherogenic diet-induced hyperlipidemia in rabbits. Journal of Integrative Medicine, 2019, 17(3): 181-191.
[5] Lucky Legbosi Nwidu, Yibala Ibor Oboma. Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress. Journal of Integrative Medicine, 2019, 17(1): 46-56.
[6] Rohitash Jamwal. Bioavailable curcumin formulations: A review of pharmacokinetic studies in healthy volunteers. Journal of Integrative Medicine, 2018, 16(6): 367-374.
[7] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Thongchai Koobkokkruad, Chutichot Pattamadilok, Nontima Vardhanabhuti . Anti-adipogenic effect of flavonoids from Chromolaena odorata leaves in 3T3-L1 adipocytes. Journal of Integrative Medicine, 2018, 16(6): 427-434.
[8] Shohini Chakraborty, Nashra Afaq, Neelam Singh, Sukanta Majumdar. Antimicrobial activity of Cannabis sativaThuja orientalis and Psidium guajava leaf extracts against methicillin-resistant Staphylococcus aureus. Journal of Integrative Medicine, 2018, 16(5): 350-357.
[9] Bruno José Martins Da Silva, Amanda Anastácia Pinto Hage, Edilene Oliveira Silva, Ana Paula Drummond Rodrigues. Medicinal plants from the Brazilian Amazonian region and their antileishmanial activity: A review. Journal of Integrative Medicine, 2018, 16(4): 211-222.
[10] Carola Analía Torres, Cristina Marisel Pérez Zamora, María Beatriz Nuñez, Ana María Gonzalez. In vitro antioxidant, antilipoxygenase and antimicrobial activities of extracts from seven climbing plants belonging to the Bignoniaceae. Journal of Integrative Medicine, 2018, 16(4): 255-262.
[11] Akintayo Lanre Ogundajo, Lateef Apollo Adeniran, Anofi Omotayo Ashafa. Medicinal properties of Ocotea bullata stem bark extracts: Phytochemical constituents, antioxidant and anti-inflammatory activity, cytotoxicity and inhibition of carbohydrate-metabolizing enzymes. Journal of Integrative Medicine, 2018, 16(2): 132-140.
[12] Bhanuz Dechayont, Arunporn Itharat, Pathompong Phuaklee, Jitpisute Chunthorng-Orn, Thana Juckmeta, Nuntika Prommee, Nitra Nuengchamnong, Pintusorn Hansakul. Antioxidant activities and phytochemical constituents of Antidesma thwaitesianum Müll. Arg. leaf extracts. Journal of Integrative Medicine, 2017, 15(4): 310-319.
[13] Bhesh Raj Sharma, Dong Wook Kim, Dong Young Rhyu. Korean Chungtaejeon tea extract attenuates weight gain in C57BL/6J-Lep ob/ob mice and regulates adipogenesis and lipolysis in 3T3-L1 adipocytes. Journal of Integrative Medicine, 2017, 15(1): 56-63.
[14] Nisha Panth, Keshav Raj Paudel, Rajendra Karki. Phytochemical profile and biological activity of Juglans regia. Journal of Integrative Medicine, 2016, 14(5): 359-373.
[15] Musa Toyin Yakubu, Abdulquadri Funmbi Olutoye. Aphrodisiac activity of aqueous extract of Anthonotha macrophylla P. Beauv. leaves in female Wistar rats. Journal of Integrative Medicine, 2016, 14(5): 400-408.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[4] Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[5] Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[6] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[7] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[8] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[9] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[10] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50