Berberine Modulates Macrophage Activation by Inducing Glycolysis.
Min LiHaifeng ZhangYameng ZhangJinting FanJinhao ZhuXinyue GuZhonghui LiChengyang ZhangZhen LiuYuebai LiMingxi ZangGe JinGuoping LiYang MiPublished in: Journal of immunology (Baltimore, Md. : 1950) (2022)
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.
Keyphrases
- blood glucose
- endothelial cells
- adipose tissue
- dendritic cells
- high fat diet induced
- inflammatory response
- magnetic resonance
- escherichia coli
- blood pressure
- magnetic resonance imaging
- mesenchymal stem cells
- type diabetes
- computed tomography
- peripheral blood
- anti inflammatory
- metabolic syndrome
- deep learning
- immune response
- wild type
- smoking cessation
- weight loss
- high intensity