Effect of Huannao Yicong Decoction extract on activity ofγsecretase and γsecretase-related regulation pathway of human APP/PS 1 double transgenic cell line / 中国药理学通报

ABSTRACT

Aim Toobservetheeffectofconcisepre-scriptions of Chinese medicine Huannao Yicong Decoc-tion(HYD)on regulatory pathway of secretase in APP/PS1 double transgenic cell line(HEK293),and to in-vestgateitsmechanism.Methods Theproliferationof AD cell model and the toxicity of each investigational drugs were ebserved by CCK-8;the changes in micro-scopic structure of each group were observed by(Trans-mission electron microscope,TEM);the activities of gamma-secretes was observed by Dual Luciferase Re-porter Gene Assay Kit ,and then the expression of pre-senilin 1(PS1),carboxyl terminus of Hsc70-interacting protein(CHIP),GTP binding protein (CDC42 ),ante-rior pharynx defective-1α(APH-1α),Hypoxia induc-ible factor-1α(HIF-1α) were detected by Western blot.Results 15%HYDserumincreasedthecellac-tivity compared to blank serum (P 0. 05 );compared to control group,HYD directly group inhibited the HIF-1αprotein ex-pression after 48h medication(P<0. 05);compared to 0h midicaiton,DAPT group inhibited the HIF-1αpro-tein expression at the point of 24 h (P<0. 05 ).Con-clusions HYDcantreatADthroughprotectingthe mitochondrial function,reducing the formation of lipo-fuscin,inhibiting the activity of γsecretase by down-regulating the activity of HIF-1α,decreasing the stabil-ity and activity of PS1 by promoting the expression of CDC42.This shows that HYD has good research and development prospect as an effective drug for preven-tion and treatment of AD.