Identification of berbamine dihydrochloride from barberry as an anti-adipogenic agent by high-content imaging assay  

作　　者：Shifeng Wang Qiao Zhang Yuxin Zhang Yanling Zhang Qinghua Wu Shiyou Li Yanjiang Qiao 

机构地区：[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100102,China [2]HD Biosciences Co.,Ltd.,Shanghai 201201,China [3]Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,1 Beichen West Road,Chaoyang District,Beijing 100101,China

出　　处：《Journal of Traditional Chinese Medical Sciences》2016年第2期91-99,共9页中医科学杂志（英文）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China(grant number 81430094).

摘　　要：Objective:Lipid droplet(LD)deposition in adipose tissue is a critical factor leading to metabolic dysfunction.Various herbal medicines in traditional Chinese medicine(TCM)are used to treat hyperlipidemia,type 2 diabetes,obesity,and other diseases.The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds.Methods:One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening.Anti-adipogenic effects of identified hits were further confirmed at various concentrations.In addition,drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds.Results:Berbamine(BBM),a chemical isolated from barberry,and a derivative of BBM,berbamine dihydrochloride(BBMD),reduced LDs formation by more than 50%.Dose-dependent effects were observed and the IC50 values of the two hits,BBM and BBMD,were determined as 1.88 mM and 0.95 mM,respectively.Moreover,BBM induced mild HepG2 cell injury,while its dihydrochloridedBBMD did not exhibit hepatotoxicity within 40 mM.Conclusion:This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

关 键 词：3T3-L1 adipocyte Berbamine dihydrochloride HEPATOTOXICITY High content screening Lipid droplet 

分 类 号：R283.6[医药卫生—中药学]