Protective Effect And Mechanism Of Ganoderic Acid A On Mice With Acute Alcoholic Liver Injury

ObjectiveTo investigate the effect of ganoderic acid A on mice with acute alcoholic liver injury and its possible mechanism.MethodsSixty mice were randomly divided into normal control group,model group,ganoderic Acid A low dose group(20 mg/kg),ganoderic Acid A high dose group(40 mg/kg)and silymarin positive control group(50 mg/kg),12/group.After 14 days of pre-administration intervention,all mice were given 30% ethanol solution(12 ml/kg)by gavage,once a day,for 3 consecutive days.Liver histopathological changes were observed by HE staining,and liver index,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST);total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)levels;liver tissue reactive oxygen species(ROS)levels,malondialdehyde(MDA)content,superoxide dismutase(SOD)activity,and glutathione(GSH)levels;serum and liver tissue interleukin-1?(IL-1?),interleukin-6(IL-6)and tumor necrosis factor-?(TNF-?)levels;Toll receptor signal pathway,NF-?B signaling pathway and expression of apoptosis-related proteins in liver tissue were determined.Results1 The liver indexes of mice in model group were significantly higher than those of mice in normal control group.The liver indexes of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than that of model group(P < 0.01).2 The levels of serum AST and ALT in model group were significantly higher than those in normal control group.The levels of serum AST and ALT in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).3 The liver cells of the model group were disordered and the nucleus staining were deepened;the liver slices of mice in silymarin positive group showed that the liver pathological degree of mice was reduced and tended to be normal;while the liver slices of mice in high dose group of ganoderic Acid A and low dose group of ganoderic Acid A showed that the liver pathological degree of mice in both groups were alleviated in varying degrees.4 The levels of serum TC,TG and LDL-C in model group were significantly higher than those in normal control group.The levels of serum TC,TG and LDL-C in ganoderic Acid A low-dose group,ganoderic Acid A high-dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).The levels of serum HDL-C in model group were significantly lower than those in normal control group,while those in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly higher than those in model group(P < 0.01).5 The levels of ROS and MDA in liver tissues of mice in model group were significantly higher than those in normal control group,while the levels of ROS and MDA in liver tissues of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).The levels of SOD and GSH in liver tissues of model group were significantly lower than those in normal control group,while those in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly higher than those in model group(P < 0.01).6 The serum levels of IL-1beta,IL-6 and TNF-alpha in model group were significantly higher than those in the normal control group.The serum levels of IL-1beta,IL-6 and TNF-alpha in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).The levels of IL-1beta,IL-6 and TNF-alpha in liver tissues of mice in model group were significantly higher than those in normal control group.The levels of IL-1beta,IL-6 and TNF-alpha in liver tissues of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).7 The expressions of TLR4,TLR2,MyD88 and NF-kappa Bp65 in liver tissue of mice in model group were significantly higher than those in normal control group.The expressions of TLR4,TLR2,MyD88 and NF-kappa Bp65 in liver tissue of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than those in model group(P < 0.01).The expression of I?B? in liver tissue of mice in model group were significantly lower than those in normal control group,while those in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly higher than those in model group(P < 0.01).8 The expression of Bax,Caspase-3 and Caspase-9 in liver tissue of mice in model group were significantly higher than that of normal control group.The expression of Bax,Caspase-3 and Caspase-9 in liver tissue of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly lower than that of model group(P < 0.01).The expression of Bcl-2 in liver tissue of mice in model group was significantly lower than that of normal control group.The expression of Bcl-2 in liver tissue of mice in ganoderic Acid A low dose group,ganoderic Acid A high dose group and silymarin positive group were significantly higher than that in model group(P < 0.01).ConclusionsGanoderic Acid A has protectice effects on alcohol-induced acute liver injury in mice,and its mechanism may be related to regulation of lipid metabolism,inhibition of oxidative stress,regulation of inflammatory response,inhibition of Toll/NF-kappa B signaling pathway and apoptotic signaling pathway proteins.