Hepatoprotective Effect Of Compound Astragalus Extract And Its Mechanism Of Action

Compound astragalus extract (CAE) is composed of active parts(Pa, Pb, Pcand Pa). In this study,the hepatoprotective effect of CAE and its mechanism of action was investegated in vivo and in vitro.Furthermore,we compared activities of the fuor parts of CEA. The main contents are as follows :1. Protective effect of CAE on D-galactosamine-induced liver injury in miceAcute liver damage model induced by D-galactosamine (D-GalN,800 mg-kg-1,ip) in mice was used in this study.The results showed that CAE (60,120 and 240 mg-kg-1,ig) could obviously lowen the elevated liver index, ALT level in serum and MDA content in liver homogenate of mice treated with D-GalN. This suggested that CAE had protective effect on D-GalN-induced acute liver injury significantly, probably being related to its anti-inflammatory and anti-oxidative effect.2. Protective effect of CAE on BCG+LPS-induced immunological liver injury in miceBCG+LPS-induced liver injury model was successlly duplicated, the results showed that CAE (120 , 240 mg-kg-1,ig) could markedly lowen the elevated ALT activity in serum and liver index, restore the diminished proliferative response of splenocyte induced by ConA and decrease the elevated IL-1, TNFa production of peritoneal macrophages from BCG+LPS treated mice. This suggested that CAE had protective effects on BCG+LPS-induced immunological liver injury significantly, probably being related to its immunomodulatory and anti-inflammatory effect.3. Inhibitory effect of CAE on function of peritoneal macrophages from normal rats in vitro.In order to find out the mechanism of the heoatoprotective effects,its effect on thefunction of peritoneal macrophages from normal rats was studied in vitro.Our results showed that CAE(11.3-90 mg-L-1) could markedly inhibit LPS-induced production of NO, TNF and IL-1 of PMS from normal rats.This suggested that CAE has direct inhibitory effect on the function of activated rat M s.4. Comparison of activities of the four parts of CAE.We also compared the effect of four parts of CAE(Pa ,Pb ,PC and Pd) on the secretory function of PM S from normal rats in vitro.The results showed that four parts of CAE all could lowen NO, TNFa and IL-1 productions of PM S induced by LPS from normal rats.The order of their inhibtory action to IL-1 and NO is Pd>Pb>Pc>Pa evaluated by IC50;and that to TNFa is Pd>Pb>Pa>Pc -This suggested that the four parts of CAE are all active,however their activities were different.On conclusion, these results indicated that CAE has markedly protective effect on D-GalN induced liver injury and immunological liver damage in mice. CAE also has inhibitory effect on the secretion of inflammatory factor such as TNFa, IL-1 and NO of PM ,from normal rats in vitro. Moreover,four parts of CAE(Pa ,Pb ,PC and Pd) all have inhibitory effect on function of PM stated above.The order of their activities to IL-1 and NO isPd>Pb>Pc>Pa evaluated by IC50, and that to TNF is Pd>Pb>Pa>Pc .These suggested that the heoatoprotective effect of CAE might be related to these as follows: l)anti-inflammatory effect and inhibiting inflammatory factors secretion of PMS directly; 2) enhancing anti-oxidative function and decreasing lipid peroxidation level; 3) immunomodulatory effect.