Mechanisms Underlying The Protection Of Neutral Sulfate Berberine Against Liver Injury Induced By Lipopolysaccharide In Mice

Objective:Berberine has been extensively studied and is known to exhibit preventive and curative effects on chemical-induced hepatotoxicity in rodents. Liver injury induced by lipopolysaccharide (LPS) is one of severe complications during sepsis, but it is unclear whether berberine protects liver against LPS-induced damage. The aim of the present study was to investigate the protective effects of neutral sulfate berberine against liver injury induced by lipopolysaccharide in mice.Methods:The male mice were divided randomly into control, neutral sulfate berberine group,LPS group and neutral sulfate berberine treatment group. Mice were administeredintragastrically with distilled water (0.01 mL/g) or 5 g/L neutral sulfate berberine (0.01mL/g) once a day for 5 days and injected intraperitoneally with normal saline or LPS(0.02 mL/g, 28 mg/kg) at 1 h after gavage on day 5.Blood was collected for determining alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the content of the tumor necrosis factors-α (TNF-α ) at 10 h and 2 h after LPS or normal saline injection, respectively . The liver tissue was processed, and histological changes and ultrastructure in liver were observed with light and electron microscopy, respectively. Furthermore, malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD) activity in liver were detected.Results:Both ALT and AST activities in serum in LPS group were higher than those in control and neutral sulfate berberine treatment group. LPS increased the serum TNF-a content at 2 h after injection, which was reversed by neutral sulfate berberine treatment. The histological examination showed LPS caused severe hepatic cell edema, degeneration, apoptosis and even necrosis, and ultrastructure observation demonstrated LPS induced mitochondrial swelling, condensation and margination of chromatin, irregular nuclear envelope in hepatocytes. The above pathological changes stimulated by LPS were attenuated by neutral sulfate berberine. Moreover, MDA contents in liver tissue were higher in LPS group than control and neutral sulfate berberine treatment group, but there were no significant difference in SOD activity and NO content between neutral sulfate berberine treatment group and LPS group.Conclusion:Neutral sulfate berberine has a protective effect on LPS-induced liver injury in mice, the mechanisms may be related to decreasing the production of TNF- a , inhibiting lipid peroxidation and protecting mitochondria.