Oyster protein hydrolysates alleviated chronic alcohol-induced liver injury in mice by regulating hepatic lipid metabolism and inflammation response.

The oyster protein hydrolysate (OPH) possesses various biological activities that have the potential to ameliorate alcoholic liver disease (ALD). This study aimed to assess the protective effects of OPH on liver injury in mice induced by chronic alcohol treatment and the underlying mechanism was further explored by transcriptome and proteome from a global view. Compared with the Model group, OPH treatment significantly decreased the liver weight (p < 0.01) and reduced the content of liver injury markers alanine aminotransferase (ALT, by 34.14%, p < 0.01), aspartate aminotransferase (AST, by 35.31%, p < 0.01) and alkaline phosphatase (ALP, by 17.18%, p < 0.05) while increased the content of hepatic function marker total protein (TP, by 17.30%, p < 0.05) in serum. Meanwhile, only mild hepatocyte injury accompanied by less lipid droplet accumulation was observed in OPH treated ALD mice. The transcriptome and proteome results indicated that 482 target genes and 111 target proteins were involved in the ameliorative effect of OPH on ALD. After data integration, 43 co-regulated targets were identified, which were mainly related to lipid metabolism (reduction of cholesterol and triglyceride accumulation) and inflammatory response [inhibition of inflammatory responses through toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and tumor necrosis factor (TNF) signaling pathways]. Consistent with omics data, the hepatic levels of total lipid, total cholesterol, triglyceride, interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) were declined by OPH treatment in ALD mice. Collectively, our results prove that OPH possesses potent hepatoprotective activities and has the potential to be used as a novel functional ingredient for the management of ALD.