The role of cAMP /Epac / Rap1 signaling pathway regulate the secretion of IL-1 β, TNF-α, BDNF from NG2 cell and the effect of Jujuboside A / 安徽医科大学学报

Objective@#To investigate whether the cyclic adenosine monophosphate (cAMP) / exchange proteins directly activated by cAMP (Epac) / ras-related protein 1 ( Rap1 ) signalling pathway is involved in the intervening mechanisms of interleukin-1 β (IL-1 β) ，tumor necrosis factor-α (TNF-α) ，brain-derived neurotrophic factor (BDNF) and Jujuboside A(JuA) secretion by NG2 cells． @*Methods@#NG2 cells were cultured in vitro and the experiment was divided into control group ，pertussis toxin ( PTX) group ，ESI-09 group，JuA group and positive drug group．The effect of different concentrations of JuA on the survival rate of NG2 cells was detected by CCK-8 method，and the expression of IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein in each group was detected by RT-PCR and Western blot. @*Results@#Compared with the control group，the PTX group decreased the expression of IL-1 β and TNF-α mRNA and protein (P＜0. 01) and increased the expression of cAMP and BDNF mRNA and protein (P＜0. 01) ; the ESI-09 group increased the expression of IL-1 β and TNF-α mRNA and protein (P < 0. 05) and decreased the expression of BDNF，Epac and Rap1 mRNA and protein expression (P＜0. 01) ; the JuA group and positive drug group increased IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein expression (P＜0. 01) ．@*Conclusion @#The cAMP / Epac / Rap1 signaling pathway is involved in the secretion of IL-1 β , TNF- α , and BDNF by NG2 cells．JuA may act on cAMP / Epac / Rap1 signaling pathway to affect the secretion of BDNF by NG2 cells.

Pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus Herb-pair Extract, in kidney-yin deficiency model

Abstract To investigate the pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus herb-pair in kidney-yin deficiency model, which was made by continuously oral gavage of thyroxine. A simple and rapid LC-MS/MS method was developed and validated for the determination of loganin and morroniside in rat plasma and used for the pharmacokinetics study. The kidney-yin deficiency significantly changed the AUC(0-∞), Cmax and CLz/F of loganin and morroniside. The T1/2z of morroniside increased significantly in the kidney-yin deficiency rats. For the pharmacodynamics study, the liver index, kidney index, and ALT, TBIL, UREA, CREA level in the kidney-yin deficiency mice were examined. The herb-pair had been proved to be effective for the treatment of kidney-yin deficiency by affecting the liver, kidney, ALT, UREA and CREA, which showed positively correlated with the dose. The pharmacokinetics and pharmacodynamics studies in the pathological status could offer more valuable information for the future application of Astragali Radix-Corni Fructus herb-pair.