In-vitro Synergistic Effect of Metformin and Berberine on High Glucose-induced Lipogenesis

Metformin and berberine have been reported to have lipid lowering effects. This study aims to investigate lipid lowering effects of berberine and metformin, alone and in combination, in HepG2 cells to determine whether berberine and metformin work synergistically and elucidate their mechanisms. HepG2 cells were treated with 33 mM glucose in the presence of various concentrations of berberine and metformin, alone and in combination, for 24 h. The cytotoxic effects of these compounds were determined by MTT assay. Oil red O staining, triglyceride measurement, and gene expression analyses were performed to evaluate the effects of these compounds on hepatocytes lipogenesis. Berberine at doses 20 µM and 40 µM and metformin at doses 1 mM  and 2 mM reduced total lipid content and triglyceride level in HepG2 cells. Metformin (mM) and berberine (µM) at combination ratios of 2:40, 1:20, 0.5:10, and 0.25:5 exhibited a synergistic lipid-lowering effect on HepG2 cells. These ratios could significantly decrease total lipid content and triglyceride level in HepG2 cells. The lowest dose of the combination [metformin (0.25 mM) and berberine (5 μM)] also synergistically reduced the expression of the FAS and SREBP-1c genes in HepG2 cells treated with high glucose. The combination of metformin and berberine exerted synergistic lipid-lowering effects on HepG2 cells by reducing total lipid content, triglyceride level, and the expression of the genes involved in lipogenesis.