Protective effect of Salvia chinensis Benth. polysaccharides on lipopolysaccharide and D-galactosamine induced acute liver failure in mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To explore the protective effect of polysaccharides from Salvia Chinensis Benth. (PSSC) on lipopolysaccharide (LPS) and D- galactosamine (GalN)- provoked mouse acute liver failure (ALF) and the possible molecular mechanism. METHODS Kunming mice were randomly divided into four groups normal control, model, model+PSSC 30 and 100 mg·kg- 1 groups. PSCC was given once a day and for a week. To establish an ALF model, mice of model and PSSC groups were ip injected with LPS 10 μg·kg-1 and GalN 700 mg·kg-1 at the end of PSSC treatment. The microscopic structure of the liver was detected by HE staining. Serum and hepatic biochemical parameters of glutamic-oxalacetic transaminase (GOT), glutamic- pyruvic transaminase (GPT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and glutathione (GSH) were detected by colorimetric methods. The relative content of hepatic reactive oxygen species (ROS) was measured by DCFH-DA fluorescent probes. Levels of cytokines tumor necrosis factor-α (TNF-α), interleukin 1β(IL-1β) and IL- 6 in the serum and liver were detected by ELISA. Activity of caspase 3 in liver homogenates was detected by aspase 3 activity assay kit. RESULTS Compared with normal control group, in the liver of model group, hepatocytes were arrayed in disorder, cytoplasm of hepatocytes shrank, and boundaries between cells were fuzzy, the infiltration of a large number of inflammatory cells and tissue hemorrhage could be detected, pathological scores were elevated significantly (P<0.01), levels of MDA and ROS in the liver of ALF model mice were elevated to 2.2 and 4.3 times that of the normal control, respectively (P<0.01), the level of GSH decreased to 51% (P<0.01), and the activities of SOD, CAT and GSH- Px declined to 74%, 36% and 42%, respectively (P<0.01). Levels of TNF- α, IL- 1β and IL- 6 in the serum and liver of model group were increased (P<0.01), and caspase 3 activity was increased to 5.3 times that of the normal control (P<0.01). Compared with the model group, the number of surviving mice in PSSC groups increased, liver pathological scores declined (P<0.01), levels of MDA and ROS increased (P<0.01), levels of GSH, TNF-α, IL-1β and IL-6 in the liver and serum declined (P<0.01), and caspase 3 activity decreased (P<0.01). CONCLUSION PSSC is able to alleviate LPS and GalN-induced ALF in mice. Inhibition of hepatic oxidative stress, inflammatory response, and cell apoptosis is possibly implicated in the protective effect of PSSC.