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Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 7, 2016; 22(1): 8-23
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.8
Table 1 The information of effects of current conventional medicines on the treatment of alcoholic liver disease
Medicine/compoundType of modelDosage/durationEffectsMechanismsRef.
CorticosteroidRCT in severe AHPrednisone (30 mg/d, 30 d)Lower mortality AH group compared to antioxidant treated group[37]
RMT and double blind trials in severe AHMethylprednisolone (32 mg within 7 d) and 28 d treatment and then tapered over 2 wk and discontinuedDecrease short-term mortality of patients with AH[160]
PentoxifyllineA double-blind, placebo-controlled trial400 mg orally 3 times daily for 4 wkDecrease in the risk of Progressing hepatorenal syndrome; Improve short-term survival in patients with AH[42]
A RCT followed by open study in severe AH patients400 mg/d, orally for 4 wk and then tapered by 5 mg/wk for 7 wkBetter reduced mortality compared to prednisolone in AH[161]
SAMEthanol-LPS-induced fibrotic rats10 mg/kg bw, ipAttenuate oxidative stress and HSC activationInhibition of TGF-β signaling pathway[50]
Double-blind, placebo-controlled trial in 220 patients with AH and cirrhosis1600 mg/d orallyDecreased serum markers of cholestasis; Improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell[162]
PPAR-α agonistsC57BL/6J mice with ethanol (27.5% of total calories)0.1% Wy-14643 for 4 wkDecreased serum and hepatic fat accumulationEnhancement of hepatic FA oxidation pathway; Increased PPAR-α mRNA expression by 5-fold[163]
C57BL/6J mice with 4 % ethanol (Ethanol feeding for 12 wk)Wy-14643 (50 mg/kg per day) for last 2 wkDecreased serum AST and ALT Dropped on score of hepatic steatosis and hepatocyte ballooningRepress PI3K and COX-2 expression; Enhance adiponectin and HO-1; Increase SIRT1 protein expression[164]
C57BL/6J mice with ethanol containing diet (29% of total calories)Rosiglitazone (3 mg/kg bw/d) for 2 wkReduced hepatic triglyceride content; Reduced AST and ALTUpregulated level of adiponectin and its receptors; Enhance SIRT1-AMPK signaling pathway[55]
MetforminC57BL/6 mice TNF knockout mice PAI-1 knockout with ethanol (6 g/kg ig)200 mg/kg ip for 4 d prior to ethanol administrationReduced ALT; Prevented hepatic fat accumulationPrevention of the upregulation of PAI-1[57]
MetadoxineHepG2, CFSC-2G and HSC treated with ethanol (50 mM) and acetaldehyde (175 µM)10µg/mL for 24 hReduced peroxidation and oxidized GSH contentDecrease collagen secretion and IL-6, IL-8 and TNF-α secretion[69]
CarvedilolMale Wistar rats with ethanol (5%) fed10 mg/kg per day for last 7 d of total 49 dReduced hepatic TG level and the accumulation of fatty droplets within hepatocytes;Down-regulated FAS and SREBP-1, and up-regulated PPAR-α;[56]
Inhibited ethanol-induced the thickening of zone 3 vessel wallsReduced the activation of HSCs with decrease induction of TGF-β1 and collagen
PropylthiouracilMale Sprague-Dawley rat with ethanol consumption (36%)50 mg/kg per day of Wy-14643 for last 2 wk for the last 5 d of 4-6 wk diets with alcoholIncreased hepatic blood flow; Reduces oxidative stress[71]
ColchicineRCT in 74 patients with cirrhosis1 mg/d for 4.4 yrReduced serum N-terminal peptide of type III procollagen levels[70]
Table 2 The information of effects of current natural medicines on the treatment of alcoholic liver disease
Medicine/compoundType of modelDosage/durationEffectsMechanismsRef.
Vitamin E and CMalnourished rats with ethanolVitamin E (15 mg/kg) Vitamin C (10 mg/kg); single and combined treatmentsDecreased ethanol induced hepatic glutathione peroxidase activity and hepatic fibrosis; Attenuated the development of hepatomegaly and hepatic necroinflammation[165]
Epigallocatechin-3-gallate (EGCG)Male albino Wistar rats with Ethanol (6 g/kg per day) for 60 dEGCG (100 mg/kg per day) for the last of 30 d of ethanol administrationNormalization of activities of enzymatic antioxidants; Reduction of lipid peroxidation[93]
Female Sprague-Dawley rats with ethanol (56%)EGCG (100 mg/bw)Partly blocked the gut leakiness; Reduced endotoxemia and lipid peroxidationBlunted the elevated expressions of CD14, TNF-α, COX-2 and iNOS[94]
Male Wistar rats with ethanol for 5 wkEGCG contained diet (3 g/L) for 2 wk and then ethanol-EGCG diet for 5 wkReduced serum AST and ALTEnhancement of FA oxidation through increasing of CTP-1 and p-ACC expression[95]
Silymarin (Silybum marianum)RCT, double-blind, 170 patients with cirrhosis140 mg/d for 3 times orallyReduced the rate of mortality No side effect[33]
Alcohol induced baboons (50% of calories)0.84 mg/calorie for 36 moImprove histologic stage of fibrosisDecrease collagen I and (I) procollagen[100]
Alcohol and high fat induced rats100 mg/kg per day, 150 mg/kg per day, 200 mg/kg per day for 6 wk200 mg/kg per day decrease serum ALT and AST and hepatic fat contentsAttenuated NF-κB p65, ICAM-1 and IL-6 were found in silymarin groups (150 mg/kg, 200 mg)[101]
BetaineEthanol diet Wistar rats1% (w/v) in dietDecrease hepatic ballooning and fat contentsAttenuate NOS production; Decrease CYP2E1 protein and activity[106]
High fat containing ethanol diet rats 6 g/kg for 8 more wk200 and 400 mg/kg per day for 4 wkDecrease ALT and ASTInhibition of TLR-4 expression; Decrease serum endotoxin, TNF-α, IFN-γ and IL-18[107]
Glycyrrhizin (Glycyrrhiza glabra)Ethanol-CCl4 induced male SD ratsIntraperitoneal injections of potenlin (acquired from Hai Ning Pharmaceutical Co., Zhe Jiang, China)Decreasing serum ALT levelsNormalized NF-κB binding activity[114]
GinsenosidesEthanol-feeding mice Ethanol feeding hepatocytes (AML12 cell lines)Red ginseng extract containing abundant ginsenosides (Rb1, Rb2, and Rd) (250 mg/kg or 500 mg/kg) for 4 wk in miceImproves chronic alcohol-induced histopathological changes; Decreases in hepatic triglyceride contentInhibition of lipogenesis pathway; Attenuated EtOH-induced cytochrome; P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels; Activation of AMPK-SIRT1[166]
Alcohol consumption with high fat diet miceRed ginseng (200 mg/kg per day) for last 2 wkLower ALT levels and no different ASTReduced level of TNF-α and IL-1 and increase IL-10[124]
Fenugreek seed polyphenolEtOH (30 mM) induced Chang liver cells20, 40, 60 mg/mLIncreased GSH/GSSG ratio Reduced EtOH-induced LDH leakageInhibition of NF-κB[129]
Ethanol induced rats (6 g/kg per day) for 30 d200 mg/kg per day for 30 dImproved lipid profile and reduced collagen content, crosslinking, aldehyde content and peroxidation[132]
CurcuminAlcohol (100 mM) induced rat primary hepatocytes0-50 μmol/LAmeliorated MDA and ASTImproved GSH and heme oxygenase-1 (HO-1) induction[133]
Alcohol-induced female Sprague-Dawley rats400 mg/kg bwImproved liver pathology, decreasing elevation of hepatic MDASuppressing of NF-κB activation[134]
LIV-52Ethanol-induced HepG2 cells (100 and 200 mM )1% or 2% Liv.52 for 24 hNormalized suppressed PPAR-α and induced TNF-α[148]