Korean J Physiol Pharmacol.  2020 Sep;24(5):385-394. 10.4196/kjpp.2020.24.5.385.

The hepato-protective effect of eupatilin on an alcoholic liver disease model of rats

• Lee HY
• Nam Y
• Choi WS
• Kim TW
• Lee J
• Sohn UD

• KMID: 2505773
• DOI: http://doi.org/10.4196/kjpp.2020.24.5.385

Abstract

Eupatilin is known to possess anti-apoptotic, anti-oxidative, and antiinflammatoryproperties. We report here that eupatilin has a protective effect onthe ethanol-induced injury in rats. Sprague–Dawley rats were divided into 6 groups:control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase(ALT) were analyzed to determine the extent of liver damage. Total cholesterol(TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis.Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH)level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor(TNF)- and interleukin (IL)-1 were quantified to verify the degree of inflammation.Based on our findings, chronic alcohol treatment significantly changed the serumindexes and liver indicators of the model rats, which were significantly improved byeupatilin treatment. Rats in the eupatilin-treatment group showed reduced levelsof AST, ALT, TG, TC, TNF-, and IL-1, increased SOD activity and GSH levels, and improvedoverall physiology compared to the alcoholic liver disease model rats. H&Estaining also verified the eupatilin-mediated improvement in liver injury. In conclusion,eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatoryeffects.

Keyword

Alcoholic liver disease; Ethanol; Eupatilin; Inflammation; Oxidative stress

Figure

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  Fig. 1 Eupatilin restored weight loss in the alcoholic liver disease model. Body weights of rats (n = 7) were measured. Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. Data are expressed as mean ± standard error of the mean. CMC-Na, sodium carboxymethyl cellulose; ALD, alcoholic liver disease. ##p < 0.01 vs. control group, *p < 0.05, **p < 0.01 vs. vehicle group.

• 

  Fig. 2 Eupatilin reduced plasma AST and ALT in the alcoholic liver disease model. (A) AST and (B) ALT levels were measured in the rat plasma (n = 7). Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. Data are expressed as mean ± standard error of the mean. CMC-Na, sodium carboxymethyl cellulose; ALD, alcoholic liver disease; AST, aspartate aminotransferase; ALT, alanine aminotransferase. ##p < 0.01 vs. control group, *p < 0.05, **p < 0.01 vs. vehicle group.

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  Fig. 3 Eupatilin reduced plasma TG and TC in the alcoholic liver disease model. (A) TG and (B) TC levels were measured in the rat plasma (n = 7). Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. Data are expressed as mean ± standard error of the mean. CMC-Na, sodium carboxymethyl cellulose; ALD, alcoholic liver disease; TG, triglyceride; TC, total cholesterol. ##p < 0.01 vs. control group, *p < 0.05, **p < 0.01 vs. vehicle group.

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  Fig. 4 Eupatilin reduced plasma MDA and improved antioxidant status in the ALD model. The activities of (A) MDA and (B) SOD and the level of (C) GSH were measured in rat plasma (n = 7). Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. Data are expressed as mean ± standard error of the mean. CMC-Na, sodium carboxymethyl cellulose; ALD, alcoholic liver disease; MDA, malondialdehyde; SOD, superoxide dismutase; GSH, glutathione. #p < 0.05, ##p < 0.01 vs. the control group, *p < 0.05, **p < 0.01 vs. the vehicle group.

• 

  Fig. 5 Eupatilin exhibited an anti-inflammatory effect by reducing the level of inflammatory cytokines. (A) TNF-α and (B) IL-1β levels were measured in rat plasma (n = 7). Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. Data are expressed as mean ± standard error of the mean. CMC-Na, sodium carboxymethyl cellulose; ALD, alcoholic liver disease; TNF, tumor necrosis factor; IL, interleukin. #p < 0.05, ##p < 0.01 vs. the control group, *p < 0.05, **p < 0.01 vs. the vehicle group.

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  Fig. 6 Eupatilin reduced oxidative stress and inflammation in the liver tissue. H&E-stained liver samples in the control, vehicle, silymarin (positive control), eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg groups. Representative photomicrographs of each sample were captured at (A) 20× (scale bar, 50 μm) and (B) 40× (scale bar, 20 μm) magnifications. The red arrow indicated the fat accumulation in liver tissue. The black arrow indicated sinusoidal dilation in liver tissue. Scale bar Control group: saline + 0.1% CMC-Na, vehicle group: 7 g/kg ethanol + 0.1% CMC-Na, silymarin (positive control) group: 7 g/kg ethanol + silymarin 10 mg/kg, eupatilin 10 mg/kg: 7 g/kg ethanol + eupatilin 10 mg/kg, eupatilin 30 mg/kg: 7 g/kg ethanol + eupatilin 30 mg/kg, and eupatilin 100 mg/kg: 7 g/kg ethanol + eupatilin 100 mg/kg. CMC-Na, sodium carboxymethyl cellulose.

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