Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Table 2 The information of effects of current natural medicines on the treatment of alcoholic liver disease

Medicine/compound	Type of model	Dosage/duration	Effects	Mechanisms	Ref.
Vitamin E and C	Malnourished rats with ethanol	Vitamin E (15 mg/kg) Vitamin C (10 mg/kg); single and combined treatments	Decreased 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 d	EGCG (100 mg/kg per day) for the last of 30 d of ethanol administration	Normalization 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 peroxidation	Blunted the elevated expressions of CD14, TNF-α, COX-2 and iNOS	[94]
	Male Wistar rats with ethanol for 5 wk	EGCG contained diet (3 g/L) for 2 wk and then ethanol-EGCG diet for 5 wk	Reduced serum AST and ALT	Enhancement of FA oxidation through increasing of CTP-1 and p-ACC expression	[95]
Silymarin (Silybum marianum)	RCT, double-blind, 170 patients with cirrhosis	140 mg/d for 3 times orally	Reduced the rate of mortality No side effect		[33]
	Alcohol induced baboons (50% of calories)	0.84 mg/calorie for 36 mo	Improve histologic stage of fibrosis	Decrease collagen I and (I) procollagen	[100]
	Alcohol and high fat induced rats	100 mg/kg per day, 150 mg/kg per day, 200 mg/kg per day for 6 wk	200 mg/kg per day decrease serum ALT and AST and hepatic fat contents	Attenuated NF-κB p65, ICAM-1 and IL-6 were found in silymarin groups (150 mg/kg, 200 mg)	[101]
Betaine	Ethanol diet Wistar rats	1% (w/v) in diet	Decrease hepatic ballooning and fat contents	Attenuate NOS production; Decrease CYP2E1 protein and activity	[106]
	High fat containing ethanol diet rats 6 g/kg for 8 more wk	200 and 400 mg/kg per day for 4 wk	Decrease ALT and AST	Inhibition of TLR-4 expression; Decrease serum endotoxin, TNF-α, IFN-γ and IL-18	[107]
Glycyrrhizin (Glycyrrhiza glabra)	Ethanol-CCl4 induced male SD rats	Intraperitoneal injections of potenlin (acquired from Hai Ning Pharmaceutical Co., Zhe Jiang, China)	Decreasing serum ALT levels	Normalized NF-κB binding activity	[114]
Ginsenosides	Ethanol-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 mice	Improves chronic alcohol-induced histopathological changes; Decreases in hepatic triglyceride content	Inhibition 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 mice	Red ginseng (200 mg/kg per day) for last 2 wk	Lower ALT levels and no different AST	Reduced level of TNF-α and IL-1 and increase IL-10	[124]
Fenugreek seed polyphenol	EtOH (30 mM) induced Chang liver cells	20, 40, 60 mg/mL	Increased GSH/GSSG ratio Reduced EtOH-induced LDH leakage	Inhibition of NF-κB	[129]
	Ethanol induced rats (6 g/kg per day) for 30 d	200 mg/kg per day for 30 d	Improved lipid profile and reduced collagen content, crosslinking, aldehyde content and peroxidation		[132]
Curcumin	Alcohol (100 mM) induced rat primary hepatocytes	0-50 μmol/L	Ameliorated MDA and AST	Improved GSH and heme oxygenase-1 (HO-1) induction	[133]
	Alcohol-induced female Sprague-Dawley rats	400 mg/kg bw	Improved liver pathology, decreasing elevation of hepatic MDA	Suppressing of NF-κB activation	[134]
LIV-52	Ethanol-induced HepG2 cells (100 and 200 mM )	1% or 2% Liv.52 for 24 h		Normalized suppressed PPAR-α and induced TNF-α	[148]

ACC: Acetyl-CoA carboxylase; AML12: Alpha mouse liver 12; AMPK: 5’ adenosine monophosphate-activated protein kinase; ALT: Alanine transaminase; AST: Aspartate aminotransferase; bw: Body weight; CCL4: Chemokine ligand 4; CD14: Cluster of differentiation 14 gene; COX-2: Cyclooxygenase-2; CPT-1: Carnitine palmitoyl-transferase 1; CYP2E1: Cytochrome P450 2E1; EGCG: Epigallocatechin-3-gallate; etOH: Ethanol; FA: Fatty acid; GSH: Glutathione; GSSG: Glutathione disulfide; HepG2: Hepatoma G2 cell-line; HO-1: Heme oxygenase-1; ICAM-1: Intercellular adhesion molecule-1; IFN-γ: Interferon-γ; IL-1: Interleukin 1; IL-6: Interleukin 6; IL-10: Interleukin-10; IL-18: Interleukin-18; iNOS: Inducible nitric oxide synthase; LDH: Lactate dehydrogenase; MDA: Malondialdehyde; NF-κB: Nuclear factor kappa; NOS: Inducible nitric oxide synthase; RCT: Randomized controlled trial; SIRT1: Sirtuin-1; TLR-4: Toll-like receptor-4; TNF-α: Tumour necrosis factor-α.