Non‐alcoholic fatty liver disease (NAFLD) has become an important health problem in the world. Natural products, with anti‐inflammatory properties, are potential candidates for alleviating NAFLD. Metformin (MET) and chlorogenic acid (CGA) have been reported to be effective in the improvement of NAFLD. Here, we aimed to evaluate the efficacy of MET and CGA combination in ameliorating NAFLD in high‐fat diet (HFD) fed mice. Fifty C57BL/6 male mice were divided into two groups, one fed a standard chow diet (n = 10) and the other was fed an HFD (n = 40) for 10 weeks. Animals in the HFD group were then randomly divided into a four groups (HFD, HFD + MET (0.25%), HFD + CGA (0.02%) and HFD + MET + CGA (0.25 + 0.02%). MET and CGA combination decreases fasting blood glucose and improves glucose intolerance. Decreased hepatic triglyceride level was associated with lower expression levels of fatty acid synthase and sterol regulatory element‐binding protein‐1c in MET+CGA treated mice. MET and CGA combination treatment resulted in the polarization of macrophages to the M2 phenotype, reduction of the expression of pro‐inflammatory cytokines (TNF‐α, IL‐1β and IL‐6), and decreasing protein level of NF‐kB p65. It was found that the lowering effect of combined MET and CGA on the expression of gluconeogenic genes was accompanied by increasing phosphorylation of glycogen synthase kinase 3β. Treatment of HFD mice with the combination of MET and CGA was found to be more effective at alleviating inflammation and lipid accumulation by increasing phosphorylation of AMP‐activated protein kinase. In conclusion, these findings suggest that the MET + CGA combination might exert therapeutic effects against NAFLD.

中文翻译：

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二甲双胍和绿原酸的组合减轻高脂饮食喂养小鼠的肝脏脂肪变性和炎症

非酒精性脂肪性肝病（NAFLD）已成为全球重要的健康问题。具有抗炎特性的天然产品是缓解 NAFLD 的潜在候选者。据报道，二甲双胍 (MET) 和绿原酸 (CGA) 可有效改善 NAFLD。在这里，我们旨在评估 MET 和 CGA 组合在改善高脂饮食 (HFD) 喂养小鼠中 NAFLD 的功效。将 50 只 C57BL/6 雄性小鼠分成两组，一组喂食标准食物 (n = 10)，另一组喂食 HFD (n = 40) 10 周。然后将HFD组中的动物随机分为四组（HFD，HFD + MET（0.25％），HFD + CGA（0.02％）和HFD + MET + CGA（0.25 + 0.02％）。MET和CGA组合减少禁食血糖和改善葡萄糖不耐受。在 MET+CGA 治疗的小鼠中，肝脏甘油三酯水平降低与脂肪酸合酶和甾醇调节元件结合蛋白-1c 的表达水平降低有关。MET 和 CGA 联合治疗导致巨噬细胞极化为 M2 表型，减少促炎细胞因子（TNF-α、IL-1β 和 IL-6）的表达，并降低 NF-kB p65 的蛋白水平。发现联合MET和CGA对糖异生基因表达的降低作用伴随着糖原合酶激酶3β磷酸化的增加。发现用 MET 和 CGA 联合治疗 HFD 小鼠可通过增加 AMP 活化蛋白激酶的磷酸化来更有效地减轻炎症和脂质积累。综上所述，