The Protective Effect Of Seven Compounds From The Roots Of Rhodiola Sachalinesis (A. Bor) Against Septic Shock And Its Mechanism

OBJECTIVE:To investigate the protective effect of seven compounds (Salidroside, Tyrosol, Ferulic acid, Kaempferol, Gallic acid, Catechin and Caffeic acid phenethyl ester) from the roots of Rhodiola sachalinesis (A. Bor) against sepsis and septic shock in mice, and research the mechanism of seven compounds against LPS-induced the macrophages RAW264.7 cells. METHODS:Male ICR mice were randomized into normal group, model group, dexamethasone group and groups treated with different doses of drugs. The model was made by intraperitoneal injected with D-GalN and LPS after 1 hour injected the drugs. After D-GalN/LPS treatment, the levels of TNF-α, IL-2 and NO, ALT, AST, and NOS activities in serum were detected. And LDH activity in liver was also evaluated. The cytoxicity of the seven compounds to macrophages RAW264.7 cells was examined using MTT test. Effects on LPS-induced pro-inflammatory mediators TNF-a, NO, PGE2 in macrophages RAW264.7 cells were assessed by ELISA. RESULTS:Salidroside 100 mg/kg group, ferulic acid 50 mg/kg, kaempferol 100 mg/kg, gallic acid 150 mg/kg, catechin 75 mg/kg and CAPE 75 mg/kg groups could significantly increased survival rate to 20%, 60%,20%,20%,40%,20% and 40% respectively in mice, All of the compounds could reduced the levels of ALT, AST and TNF-αin serum. Salidroside, tyrosol 25 mg/kg, kaempferol 100 mg/kg, gallic acid 150mg/kg, catechin 100 mg/kg and CAPE 75 mg/kg groups decreased NO and i-NOS, but no effect to T-NOS activity. Tyrosol 25 mg/kg, kaempferol 100 mg/kg, ferulic acid 50 mg/kg, gallic acid 150 mg/kg and catechin 100 mg/kg groups reduced the levels of LDH in mice liver than model groups, tyrosol 50μm, kaempferol 100μm and 50μm, catechin 50μm and gallic acid 100μM showed inhibitory effects on the levels of NO, PGE2 and TNF-α, and inhibited i-NOS and COX-2 protein expression in LPS-induced macrophages RAW264.7 cells. CONCLUSIONS:Seven compounds showed remarkable protective effects on D-GalN/LPS-induced sepsis and septic shock in mice. It may be through decreasing the contents of NO and TNF-α, and reducing the levels of i-NOS, LDH, ALT and AST. Six compounds have obvious inhibition to various kinds of pro-inflammatory mediators in LPS-induced macrophages RAW264.7 cells. It may be through inhibiting NOS and COX-2 protein expression, decreasing the content of NO and PGE2.