Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease  

作　　者：Jia Meng Sai-zhen Wang Jin-zhao He Shuai Zhu Bo-yue Huang Shu-yuan Wang Min Li Hong Zhou Shu-qian Lin Bao-xue Yang 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Department of Pharmacology,School of Basic Medical Sciences,Peking University,Beijing 100191,China [2]Fuzhou Institute of Green Valley Bio-Pharm Technology,Fuzhou 350002,China [3]JUNCAO Technology Research Institute,Fujian Agriculture and Forestry University,Fuzhou 350002,China [4]Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education,Beijing 100191,China

出　　处：《Acta Pharmacologica Sinica》2020年第6期782-790,共9页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China grants 81620108029,81330074,81261160507,81170632,and 81873597 and the Beijing Natural Science Foundation grant 7172113.

摘　　要：Autosomal dominant polycystic kidney disease(ADPKD)is one of the most common life-threatening monogenetic diseasescharacterized by progressive enlargement of fluid-filled renal cysts.Our previous study has shown that Ganoderma triterpenes(GT)retards PKD renal cyst development.In the present study we identified the effective ingredient of GT in suppression of kidney cystdevelopment.Using an in vitro MDCK cystogenesis model,we identified ganoderic acid A(GA-A)as the most promising candidateamong the 12 ganoderic acid(GA)monomers.We further showed that GA-A(6.25-100μM)significantly inhibited cyst growth inMDCK cyst model and embryonic kidney cyst model in vitro,and the inhibitory effect was reversible.In kidney-specific Pkd1knockout(kPKD)mice displaying severe cystic kidney disease,administration of GA-A(50 mg·kg^-1·d^-1,sc)significantly attenuatedrenal cyst development.In both MDCK cells and kidney of kPKD mice,we revealed that GA-A dose-dependently downregulated theRas/MAPK signaling pathway.The expression of proliferating cell nuclear antigen(PCNA)was also suppressed,suggesting apossible effect of GA-A on cell proliferation.These experimental data suggest that GA-A may be the main ingredient of GT as apotential therapeutic reagent for treating ADPKD.

关 键 词：ADPKD Ganoderma triterpenes Ganoderic acids Ganoderic acid A MDCK kPKD mice Ras/MAPK signaling pathway 8-BR-CAMP 

分 类 号：R285[医药卫生—中药学]