Abstract: Protocatechuic acid (PCA) is one of the main metabolites of anthocyanins in the body and has good anti-inflammatory activity. In this study, the protective effect of oral administration of PCA at a dose of 100 mg/(kg mb·d) on high-fat diet (HFD)-induced liver inflammation in C57BL/6J mice was investigated, and the underlying mechanism was investigated by in vitro experiments. In vivo studies showed that after 12 weeks of PCA intervention, the body mass and liver fat content of HFD-fed C57BL/6J mice were significantly reduced, and so were the levels of inflammatory factors such as interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS) in serum and liver. In vitro transcriptome sequencing (RNA-Seq) and Western blot analysis of primary hepatocytes and livers demonstrated that PCA could significantly reduce the gene and protein expression of Toll like receptor 4 (TLR4), and then down-regulate the phosphorylation of nuclear transcription factor κB (NF-κB) inhibiting the expression of inflammatory factors such as IL-6. These results suggest that PCA can effectively improve HFD-induced liver inflammation, possibly by down-regulating the TLR4/NF-κB signaling pathway.

Key words: protocatechuic acid; hepatic inflammation; RNA sequencing; Toll like receptor 4; nuclear factor κB