Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation

Abstract

Objective. This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice. Methods. We administered GalN (650 mg/kg) together with LPS (30 μg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis. Results. It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect. Conclusion. Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.

Key Words::

• acute liver injury
• apoptosis, inflammation
• D-galactosamine
• echinacoside
• lipopolysaccharide

Acknowledgments

This work was supported by National Natural Science Foundation of China (81372094) to Dr Tao Wen; by Beijing Municipal Science and Technology Activities Preferred Overseas Personnel Project (to Tao Wen); by Beijing Municipal Health System High-level Talent Training Project (to Tao Wen); and by National TCM Project Application in the 11th Five-Year Period (2008 ZX10005-007, 200907001-3 to Dr Xiuhui Li), and Beijing Municipal Science and Technology Plan Project (D08050700630802) to Dr Xiuhui Li; and by National Science Technology Major Program (2012ZX10005005-001-012) and by Beijing Municipal Natural Science Foundation (7132105) to Dr Xiuhui Li. The authors thank Professor Mark Newman (director of State and Federal Policy at Oklahoma State Department of Health) for his help in editing the manuscript for language.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.