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Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions. According to the “two-stage hypothesis” proposed for the pathophysiology of NAFLD, insulin resistance, oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here, ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms, such as sensitizing insulin effects, activating peroxisome prolifer- ator-activated receptor γ which induces adiponectin and down-regulates pro-inflammatory cytokines, changing the balance between adiponectin and tumor necrosis factor-α in favor of adiponectin, promoting considerable antioxidant effects and antidyslipidemic properties, and reducing hepatic triglyceride content which can prevent steatosis. The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD. Therefore, conducting trials to explore its ben- efits in clinical practice is greatly recommended.

 

Sahebkar A. Potential efficacy of ginger as a natural supple- ment for nonalcoholic fatty liver disease. World J Gastroenterol 2011; 17(2): 271-272 Available from: URL: http://www.wjg- net.com/1007-9327/full/v17/i2/271.htm DOI: http://dx.doi. org/10.3748/wjg.v17.i2.271

 

 

To The ediTor

Nonalcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is growing fast into an epi- demic problem in Western countries. NAFLD, covering a wide spectrum of hepatic conditions from simple steato- sis to nonalcoholic steatohepatitis (NASH), may lead to more severe disorders such as cirrhosis and hepatocellular carcinoma. The pathophysiology of NAFLD has been conceptualized to be a two-stage process, consisting of fat accumulation in hepatocytes and consequent hepatic ste- atosis in the first stage, and hepatic injury or NASH in the second stage. Insulin resistance plays a central role in both stages of NAFLD pathogenesis while oxidative stress and pro-inflammatory cytokines [in particular tumor necrosis factor (TNF)-α] are among the important promoters of the second stage.

Ginger (underground rhizomes of Zingiber officinale) is a famous spice which has been used for centuries as a me- dicinal plant in different traditional medicine systems. The therapeutic effects of ginger have also been validated by modern research, rendering it as a potential medication for a variety of disorders. Gingerols and shogaols represent the predominant pungent constituents of ginger responsible for many of its medicinal properties. Herewith, it is hypoth-

 

 

esized that ginger might be applied as a potential natural medicine that could counteract the biochemical abnormali- ties involving the pathogenesis of NAFLD as follows.

Insulin resistance is a common feature in patients with NAFLD and NASH. Regarding the key role of in- sulin resistance and resulting hyperinsulinemia in hepatic triglyceride accumulation, insulin sensitizing is an impor- tant therapeutic mechanism against NAFLD. A previous preliminary study reported that the insulin sensitivity to adipocytes could be improved using ginger, with gingerol as its active component for this effect[1].

It is considered that peroxisome proliferator-activated receptors α (PPARα) and γ (PPARγ) can influence hepat- ic triglyceride accumulation and thereby pathogenesis of NAFLD. It was reported that PPARγ can improve insulin sensitivity and decrease the flux of fatty acids into liver[2]. Moreover, PPARγ activation is associated with other ben- eficial effects such as induction of adiponectin expression and secretion, and down-regulation of the expression of pro-inflammatory cytokines including TNF-α. Hence, PPARγ agonists have been hypothesized to be of thera- peutic importance in NAFLD[2]. Noteworthy, ginger’s 6-shogaol has been reported to be a significant agonist of PPARγ in adipocytes[3].

Previous studies showed that both TNF-α and adi- ponectin play an important role in the development of hepatic steatosis and in its progression to NASH[4,5]. These cytokines have conflicting activities and antagonize each other’s production and effects. While adiponectin has sev- eral protective effects against NAFLD such as improve- ment of insulin resistance and reduction of fat accumula-

tion in hepatocytes. TNF-α antagonizes these effects and promotes hepatic steatosis. Therefore, down-regulation of TNF-α may be a potential approach to the treatment of NAFLD and amelioration of liver damage. Ginger is deemed to be effective for this purpose as several previous studies have shown that ginger extract and its bioactive constituents can decrease the TNF-α expression[6,7]. More- over, it has been found that both 6-gingerol and 6-shogaol can significantly inhibit TNF-α mediated down-regulation of adiponectin expression[3].

Along with cytokines, oxidative stress also plays an important role in the second stage of NAFLD, mediating the progression of hepatic steatosis to NASH. Therefore, antioxidants such as vitamin E have gained therapeutic ap- plication in the treatment of NAFLD. In addition to the other benefits mentioned, ginger possesses considerable antioxidant properties including radical scavenging activity and inhibitory effect on lipid peroxidation, which can be ascribed to the presence of polyphenols such as gingerol and curcumin in this plant[8]. Besides, ginger protects the liver against hepatotoxic agents by enhancing the hepatic antioxidant activity[9,10].

Triglyceride accumulation in hepatocytes is the hall- mark of NAFLD. There is evidence that ginger can re- duce hepatic triglyceride content, induce LDL receptor and down-regulate HMG-COA expression in the liver[11].

 

Moreover, ginger extract has been reported to exert its anti-hyperlipidemic effects by decreasing serum levels of total cholesterol, LDL-C and triglycerides and increasing HDL-C[12]. Thus, supplementation with ginger might be effective in the prevention of steatosis and control of dys- lipidemia which is a risk factor for NAFLD[10].

In spite of the aforementioned interesting potentials of ginger, the efficacy of this wonderful spice has not been sufficiently investigated in relation to NAFLD. Giv- en the long reputation of ginger as a medicinal herb and dietary spice with a good safety, tolerability and low price, future clinical trials are warranted to identify its efficacy as a multifunctional adjunctive therapy for NAFLD.

 

reFereNCeS

1. Sekiya K, Ohtani A, Kusano S. Enhancement of insulin sensi- tivity in adipocytes by ginger. Biofactors 2004; 22: 153-156
2. Kallwitz ER, McLachlan A, Cotler SJ. Role of peroxisome proliferators-activated receptors in the pathogenesis and treat- ment of nonalcoholic fatty liver disease. World J Gastroenterol 2008; 14: 22-28
3. Isa Y, Miyakawa Y, Yanagisawa M, Goto T, Kang MS, Kawada T, Morimitsu Y, Kubota K, Tsuda T. 6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downreg- ulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2008; 373: 429-434
4. Polyzos SA, Kountouras J, Zavos Ch. The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in non alcoholic fatty liver disease. Hippokratia 2009; 13: 127; author reply 128
5. Trappoliere M, Tuccillo C, Federico A, Di Leva A, Niosi M, D’Alessio C, Capasso R, Coppola F, Dauria M, Loguercio C. The treatment of NAFLD. Eur Rev Med Pharmacol Sci 2005; 9: 299-304
6. Lee TY, Lee KC, Chen SY, Chang HH. 6-Gingerol inhibits ROS and iNOS through the suppression of PKC-alpha and NF-kappaB pathways in lipopolysaccharide-stimulated mouse macrophages. Biochem Biophys Res Commun 2009; 382: 134-139
7. Habib SH, Makpol S, Abdul Hamid NA, Das S, Ngah WZ, Yusof YA. Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats. Clinics (Sao Paulo) 2008; 63: 807-813
8. Stoilova I, Krastanov A, Stoyanova A, Denev P, Gargova S. Antioxidant activity of a ginger extract (Zingiber officinale). Food Chem 2007; 102: 764-770
9. Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by en- hancing hepatic antioxidant status. Food Chem Toxicol 2007; 45: 2267-2272
10. Mallikarjuna K, Sahitya Chetan P, Sathyavelu Reddy K, Rajendra W. Ethanol toxicity: rehabilitation of hepatic antioxi- dant defense system with dietary ginger. Fitoterapia 2008; 79: 174-178
11. Nammi S, Kim MS, Gavande NS, Li GQ, Roufogalis BD. Regulation of low-density lipoprotein receptor and 3-hy- droxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats. Basic Clin Pharmacol Toxicol 2010; 106: 389-395
12. Ahmida MH, Abuzogaya MH. The effects of oral administra- tion of green tea and ginger extracts on serum and hepatic lipid content in rats fed a hyperlipidemic diet. J Appl Sci Res 2009; 5: 1709-1713

S- Editor Tian L   L- Editor Wang XL    E- Edito[/su_expand]