Center for Creative Biomedical Scientists at Chonnam National University, Republic of Korea; Research Institute of Medical Sciences, Chonnam National University, Republic of Korea.
Departments of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 5 Hak-dong, Gwangju 501-746, Republic of Korea; Center for Creative Biomedical Scientists at Chonnam National University, Republic of Korea.
Eur J Pharmacol. 2014 Apr 5;728:176-82. doi: 10.1016/j.ejphar.2014.01.039. Epub 2014 Jan 31.
AMP-activated protein kinase (AMPK) plays an important role in inflammation in various cells and increases the phagocytic ability of macrophages. In this study, we found that sauchinone increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in mouse peritoneal macrophages. Sauchinone increased macrophage phagocytosis of fluorescent Escherichia coli, which was blocked by compound C, an AMPK inhibitor. Sauchinone also increased the phosphorylation of p38 mitogen activated protein kinase (MAPK) in cultured macrophages in a concentration-dependent fashion, which was not blocked by compound C. However, the increase of sauchinone-induced phagocytosis was prevented by SB203580. An inhibitor of the upstream kinase TGF-beta-activated kinase (TAK1), (5z)-7-oxozeaenol, abolished the phosphorylation of ACC and p38 MAPK. Systemic administration of sauchinone to mice led to increased phosphorylation of AMPK and p38 MAPK in the lung, and enhanced phagocytosis of fluorescent E. coli in bronchoalveolar lavage fluid as compared with control mice. These results suggest sauchinone to be a useful adjunctive treatment for bacterial infection.
腺苷酸活化蛋白激酶 (AMPK) 在各种细胞的炎症反应中发挥重要作用，并能提高巨噬细胞的吞噬能力。在本研究中，我们发现莪术二酮能增加小鼠腹腔巨噬细胞中 AMPK 及其下游靶标乙酰辅酶 A 羧化酶 (ACC) 的磷酸化。莪术二酮能增加巨噬细胞对荧光大肠杆菌的吞噬作用，而 AMPK 抑制剂 Compound C 则能阻断该作用。莪术二酮还能浓度依赖性地增加培养的巨噬细胞中 p38 丝裂原活化蛋白激酶 (p38 MAPK) 的磷酸化，而 Compound C 并不能阻断这一作用。然而，SB203580 能阻止莪术二酮诱导的吞噬作用增加。上游激酶 TGF-β 激活激酶 (TAK1) 的抑制剂 (5z)-7-氧杂豆甾醇能消除 ACC 和 p38 MAPK 的磷酸化。与对照组小鼠相比，莪术二酮在体内给药能增加小鼠肺部的 AMPK 和 p38 MAPK 的磷酸化，并增强支气管肺泡灌洗液中荧光大肠杆菌的吞噬作用。这些结果表明莪术二酮可能是治疗细菌感染的一种有效辅助药物。
