Thymol ameliorates ethanol-induced hepatotoxicity via regulating metabolism and autophagy.

Alcoholic liver disease represents a serious threat to human health. In terms of safety and acceptability, thymol is widely used in or on foodstuffs to generate odour and taste. The present study aimed to investigate the therapeutic effect and mechanism of thymol against ethanol-induced injury in liver cells. Here we found that thymol is an effective agent for reducing ethanol-induced reactive oxygen species production in mouse liver cells. Thymol improves ethanol-induced lipid accumulation, and this corresponded to altered DGAT2 mRNA expression levels. Metabolomics data analysis showed that thymol alleviated ethanol-induced changes in the levels of thirty-four metabolites including nicotinic acid and l-arginine. By utilizing pathway enrichment analysis, altered metabolites in cells treated with ethanol and ethanol plus thymol were enriched in fourteen pathways including metabolic pathways and arginine and proline metabolism. We further confirmed the alleviation of overdose nitric oxide production in cells treated with ethanol plus thymol compared with that in ethanol-treated cells. It was interesting that up-regulated LC3-II/LC3-I ratio together with higher SQSTM1 protein abundance in ethanol-treated cells were attenuated by treatment with ethanol plus thymol. Thymol ameliorated ethanol-induced reduction of HSPA8 protein abundance. In addition, chloroquine-treated cells exhibited lower HSPA8 protein abundance compared with cells simulated with ethanol plus thymol. These data reveal that improving effect of thymol on ethanol-induced metabolic alteration is related to autophagic flux restoration. Our findings indicate that thymol is an attractive option for treating ethanol-induced liver damage.

Aldose Reductase Inhibitors of Plant Origin in the Prevention and Treatment of Alcoholic Liver Disease: A Minireview.

Alcoholic liver disease (ALD) is caused by heavy alcohol consumption over a long period. Acetaldehyde-mediated toxicity, oxidative stress, and imbalance of lipid metabolism are generally considered involved in the initiation of ALD. There is an increasing requirement for alternative and natural medicine to treat ALD. Recently, aldose reductase (AR) has been reported to be involved in the development of ALD by affecting inflammatory cytokines, oxidative stress, and lipid metabolism. Here, we review the effect of plant-derived AR inhibitors on ALD in rodents. And we conclude that AR inhibitors of plant origin may enhance antioxidant capacity, inhibit lipid peroxidation and inflammatory cytokines expression, and activate AMP-activated protein kinase thereby subsequently suppressing alcohol-induced lipid synthesis in liver to achieve ALD protection. This review reveals that natural AR inhibitor may be potential therapeutic agent for ALD.