Metformin improves lipid profile, however, combination therapy is developing to increase its effectiveness and reduce the deleterious effects of metformin. Chlorogenic acid (CGA) has exhibited lipid-lowering effects. This study aimed to investigate the combined effect of metformin and CGA on lipid accumulation, as well as to elucidate the engaged mechanism in HepG2 cells. To find the non-lethal doses of metformin and CGA, MTT assay was performed. High Glucose (HG) at 33 mM was used to induce lipogenesis in HepG2 cells. Following treatment with different concentrations of metformin and CGA, total lipid content (Oil Red O-staining), triglyceride level, the genes expression of SREBP-1c and FAS, and phosphorylation of AMPK and ACC were measured. Both Metformin and CGA decreased HG-induced lipid accumulation individually, by decreasing total lipid content and triglyceride level. The lowest effective doses of metformin and CGA were 0.25 mM and 5 μM, respectively, which significantly reduced SREBP-1c and FAS genes expression. The combination of these concentrations reinforced these effects. The phosphorylation of AMPK and ACC were more increased by metformin in combination with CGA than both individually. Our findings suggest that CGA synergistically enhances metformin lipid reducing action via the regulating of involved factors in fatty acid synthesis. Therefore, co-administration of metformin with CGA may have further medical value in treating lipid metabolism disorders.

二甲双胍可改善血脂，然而，正在开发联合疗法以提高其有效性并减少二甲双胍的有害作用。绿原酸 (CGA) 具有降脂作用。本研究旨在探讨二甲双胍和 CGA 对脂质积累的联合作用，并阐明 HepG2 细胞的参与机制。为了找到二甲双胍和 CGA 的非致死剂量，进行了 MTT 测定。33 mM 的高葡萄糖 (HG) 用于诱导 HepG2 细胞中的脂肪生成。在用不同浓度的二甲双胍和 CGA 处理后，测量总脂质含量（油红 O 染色）、甘油三酯水平、SREBP-1c 和 FAS 的基因表达以及 AMPK 和 ACC 的磷酸化。二甲双胍和 CGA 分别降低了 HG 诱导的脂质积累，通过降低总脂质含量和甘油三酯水平。二甲双胍和 CGA 的最低有效剂量分别为 0.25 mM 和 5 μM，显着降低了 SREBP-1c 和 FAS 基因的表达。这些浓度的组合强化了这些效果。二甲双胍与 CGA 联合使用比单独使用更能增加 AMPK 和 ACC 的磷酸化。我们的研究结果表明，CGA 通过调节脂肪酸合成中的相关因子协同增强二甲双胍的降脂作用。因此，二甲双胍与 CGA 的联合给药可能在治疗脂质代谢紊乱方面具有进一步的医学价值。这些浓度的组合强化了这些效果。二甲双胍与 CGA 联合使用比单独使用更能增加 AMPK 和 ACC 的磷酸化。我们的研究结果表明，CGA 通过调节脂肪酸合成中的相关因子协同增强二甲双胍的降脂作用。因此，二甲双胍与 CGA 的联合给药可能在治疗脂质代谢紊乱方面具有进一步的医学价值。这些浓度的组合强化了这些效果。二甲双胍与 CGA 联合使用比单独使用更能增加 AMPK 和 ACC 的磷酸化。我们的研究结果表明，CGA 通过调节脂肪酸合成中的相关因子协同增强二甲双胍的降脂作用。因此，二甲双胍与 CGA 的联合给药可能在治疗脂质代谢紊乱方面具有进一步的医学价值。