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 diabet...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.展开更多
以L-天冬氨酸为原料,经缩合得N-甲酰-L-天冬氨酸酐,然后经酰化、酯化、还原、成环得(S)-1-苄基-3-氨基吡咯烷,最后脱苄合成(S)-(+)3-氨基吡咯烷二盐酸盐,总收率62.8%。考察了工艺条件对反应的影响。(S)-1-苄基-3-氨基吡咯烷适宜工艺条件...以L-天冬氨酸为原料,经缩合得N-甲酰-L-天冬氨酸酐,然后经酰化、酯化、还原、成环得(S)-1-苄基-3-氨基吡咯烷,最后脱苄合成(S)-(+)3-氨基吡咯烷二盐酸盐,总收率62.8%。考察了工艺条件对反应的影响。(S)-1-苄基-3-氨基吡咯烷适宜工艺条件为:n(KBH4)∶n(H2SO4)∶n(混合物4)=3∶1.5∶1,反应温度50～60℃,反应时间6h,收率71.6%。产物结构经MS和1 H NMR进行确证。展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China(grant number 81430094).
文摘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.
文摘以L-天冬氨酸为原料,经缩合得N-甲酰-L-天冬氨酸酐,然后经酰化、酯化、还原、成环得(S)-1-苄基-3-氨基吡咯烷,最后脱苄合成(S)-(+)3-氨基吡咯烷二盐酸盐,总收率62.8%。考察了工艺条件对反应的影响。(S)-1-苄基-3-氨基吡咯烷适宜工艺条件为:n(KBH4)∶n(H2SO4)∶n(混合物4)=3∶1.5∶1,反应温度50～60℃,反应时间6h,收率71.6%。产物结构经MS和1 H NMR进行确证。
