Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice.

OBJECTIVE

To investigate the potential protective effects of chlorogenic acid (CGA) on acute liver injury caused by lipopolysaccharide (LPS) in mice.

METHODS

C57BL/6J mice were pretreated with CGA (50 mg/kg, intraperitoneally) once per day for 5 days before an overnight LPS challenge (30 mg/kg, intraperitoneally). Severity of liver injury was assessed by histological analysis and determination of serum ALT and AST levels. Expression and activation of key regulators involved in the inflammatory response were determined, respectively, by real-time RT-PCR and western blotting.

RESULTS

In contrast to the yellow color of the liver in LPS-treated mice, CGA maintained the normal reddish appearance of the liver. Histological analysis indicated that CGA attenuated the infiltration of neutrophil cells and the necrosis of hepatocytes. CGA also decreased the elevated plasma levels of ALT and AST. At the transcriptional level, CGA pretreatment suppressed hepatic mRNA expression of toll-like receptor 4 (TLR4), TNF-alpha and NF-kappaB p65 subunit. In contrast, mRNA level of the transcriptional coactivator PGC-1alpha was restored by CGA. Finally, CGA reduced the phosphorylation of NF-kappaB p65 subunit in the liver.

CONCLUSIONS

Our data suggest that CGA has remarkable hepatoprotective effects on LPS-induced liver injury and that the possible mechanism is related to its anti-inflammatory action.