Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors  

作　　者：Zi-ru Yu Wei-hua Jia Chao Liu Hong-qing Wang Hai-guang Yang Guo-rong He Ruo-yun Chen Guan-hua Du 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Beijing Key Laboratory of Drug Target and Screening Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Acta Pharmacologica Sinica》2020年第4期516-522,共7页中国药理学报（英文版）

基　　金：supported by the CAMS Innovation Fund for Medical Sciences(2017-I2M-1-010,China);the Drug Innovation Major Project(2018ZX09711001-003-005,China);the Peking Union Medical College Graduate Innovation Fund Project(2017-1007-11).

摘　　要：Excessive nitric oxide(NO)causes extensive damage to the nervous system,and the adrenergic system is disordered in many neuropsychiatric diseases.However,the role of the adrenergic system in protection of the nervous system against sodium nitroprusside(SNP)injury remains unclear.In this study,we investigated the effect of ganoderic acid A(GA A)against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection.We found that SNP(0.125?2mM)dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents.Pretreatment with GA A(10μM)signi?cantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells,but not in PC12 cells.Furthermore,pretreatment with GA A caused signi?cantly higher adrenaline content in SH-SY5Y cells than in PC12 cells.In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells,we added adrenaline,phentolamine,metoprolol,or ICI 1185511 h before GA A was added to the culture medium.We found that addition of adrenaline(10μM)signi?cantly improved GA A protection in PC12 cells.The addition ofβ1-adrenergic receptor antagonist metoprolol(10μM)orβ2-adrenergic receptor antagonist ICI 118551(0.1μM)blocked the protective effect of GA A,whereas the addition ofα-adrenergic receptor antagonist phentolamine(0.1μM)did not affect GA A protection in SH-SY5Y cells.These results suggest thatβ-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries,and excessive adrenaline system activation caused great damage to the nervous system.

关 键 词：β-adrenergic receptors sodium nitroprusside(SNP) SH-SY5Y CELLS PC12 CELLS ganoderic acid A ADRENALINE norepinephrine PHENTOLAMINE METOPROLOL ICI 118551 

分 类 号：R965[医药卫生—药理学]