Zeaxanthin Dipalmitate in the Treatment of Liver Disease

Table 2

Studies using zeaxanthin dipalmitate and zeaxanthin.

Experimental drug	Model	Experiement duration	Dose (ZD or ZE) and course of treatment	Case/control	Disease type	Method	Efficacy	Control	ZD side effect	Reference	Reference #
ZD	Hepatocytes of Wistar rats	25.5 hours	0.1 μM; 1 μM; 10 μM	NA	ALD/ethanol-induced liver injury	Cell culture in 10 nM CCI4-containing medium	Inhibited ALT and SDH in a dose-dependent manner	Unchallenged and untreated cells	None	Kim	66
ZE			0.1 μM; 1 μM; 10 μM	NA	ALD/ethanol-induced liver injury	Cell culture in 10 nM CCI4-containing medium	Inhibited ALT and SDH in a dose-dependent manner	Unchallenged and untreated cells	None
ZD	Wistar rats	6 weeks	12.5 mg/kg/d; 25.0 mg/kg/d	16/5	Hepatic fibrosis (secondary biliary fibrosis	Bile duct ligation	25 mg/kg significantly reduced collagen content in the liver. TBARS decreased. Elevated serum ALT significantly decreased at 25.0 mg/kg	Sham operation	None	Kim	57
ZE	Mongolian gerbils	6 weeks	12.5 mg/kg/d; 25.0 mg/kg/6	18/6	NASH	MC diet	Decreased oxidative stress and liver fibrosis in a dose-dependent manner. 25 mg/kg/d inhibited fibrosis	Regular chow	None	Chamberlain	58
ZE + LU	Population-based study	4 year and 8 months: July 2008–June 2010 and April 2011–January 2013	NA	2,935/NA	NASH	NA/Regular diet	High serum levels of ZE + LU significantly and inversely correlated with NAFLD severity	NA	None	Cao	77
ZD	Transgenic balb/c mice; wild-type balb/c mice	8 weeks	2 mg/kg for three days a week	70/10	NASH + HBV	MC diet and HBV transgenic mouse phenotype	Restored body weight. Inhibited oxidative stress. Regulated liver enzyme levels. Lowered production HBV DNA replication and serum HBsAg levels	Regular chow	None	Li	60
ZD	Sprague–Dawley rats	10 weeks	25 mg/kg/d from 5 to 10th week	18/6	AFLD	Intragastrically fed 4.0 g/kg ethanol diluted in water for 10 weeks	Restored body weight. Improved liver histology. Decreased inflammation and apoptosis. Reduced hepatic oxidative stress. Did not change blood alcohol level	Regular chow	None	Xiao	59
ZD	Sprague–Dawley rats; BRL-2A cells	6 weeks	Experiments: in vitro: 1 μM. AFLD animal model: 10 mg/kg/d for 2 weeks; systemic autophagy inhibition model: 10 mg/kg/d for 6 weeks; knockdown of P2X7 and AdipoR1: 10 mg/kg/d for 6 weeks	48/16 (not clear)	AFLD	Lieber-DeCarli liquid diet with ethanol intake increased gradually and maintained at 5% (w/v)	Induced mitophagy. Inhibited the P13 K/AKT pathway and restored AMPK/Fox3a. Partially inhibited NLRP3 inflammasome	Dextrin/maltose-based liquid diet	None	Gao	99
ZE	AH109A cells	2 months	5 μM	NA	Hepatocellular carcinoma	AH109 A cells cultured in Donryu rats’ peritoneal cavity and harvested for in vitro assays	Inhibited AH109 A cell invasion through its antioxidant properties. ZE may remain in the cell membrane	Control medium 0.5% DSMO alone	None	Kozuki	103
ZD	Human adipose-derived mesenchymal stem cells (hADMSC); nonobese/diabetic severe combined immunodeficient (NOD/SCID) mice	1 week	0.5 μM	84/12	Liver failure	Intraperitoneal injection of nonobese diabetic severe combined immunodeficient mice with pretreated stem cells	Optimized stem cell therapy in animal model. Improved stem cell visibility ratio and decreased apoptosis. Upregulated miR-210 expression. Reduced the activity of caspases 3/7 and 8 and recovered GSH/GSSG and CAT/SOD1 levels	Intraperitoneal injection with PBS only	None	Liu	111