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

• Main Authors: Shifeng Wang, Qiao Zhang, Yuxin Zhang, Yanling Zhang, Qinghua Wu, Shiyou Li, Yanjiang Qiao
• Format: Article
• Language: English
• Published: Elsevier 2016-04-01
• Series: Journal of Traditional Chinese Medical Sciences
• Subjects: 3T3-L1 adipocyte; Berbamine dihydrochloride; Hepatotoxicity; High content screening; Lipid droplet
• Online Access: http://www.sciencedirect.com/science/article/pii/S2095754816300151

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 μM and 0.95 μM, respectively. Moreover, BBM induced mild HepG2 cell injury, while its dihydrochloride—BBMD did not exhibit hepatotoxicity within 40 μM. Conclusion: This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.