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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 # |
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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 |
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