Classical activation of macrophage and monocyte differentiation induced by β-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow–derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.

由β-葡聚糖诱导的巨噬细胞和单核细胞分化的经典激活伴随着葡萄糖的代谢变化。然而，代谢重连在单核细胞/巨噬细胞活化中的作用仍然难以捉摸。在这项研究中，我们表明小檗碱通过阻断三羧酸循环来诱导有氧糖酵解，并调节来自小鼠和人 PBMC 的骨髓衍生巨噬细胞 (BMDM) 中的细胞因子反应。13-Methyberberine 对葡萄糖代谢和 BMDM 活化具有与小檗碱相似的活性，而其他测试的衍生物则失去这两种活性。在小檗碱存在的情况下，BMDMs 中的葡萄糖转运蛋白 (GLUT)1 表达和总细胞己糖激酶活性逐渐增加。相比之下，LPS 在 6 小时内上调 GLUT1 和 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) 水平。细胞外葡萄糖水平和培养基中用半乳糖替代葡萄糖会影响 BMDMs 的细胞因子分泌。小檗碱缓解肠炎鼠伤寒沙门氏菌感染并保护小鼠免受内毒素休克。在腹腔注射LPS的小鼠中，小檗碱处理可减轻血清TNF-α的升高和血糖的下降。这些数据共同表明巨噬细胞活化与葡萄糖代谢密切相关。