Kim Hong Min, Kwon Mi-Hye, Lee Eun Soo, Ha Kyung Bong, Chung Choon Hee
Astrogen Inc., Daegu, Korea.
The East Coast Research Institute of Life Science, Gangneung-Wonju National University, Gangneung, Korea.
J Yeungnam Med Sci. 2024 Apr;41(2):103-112. doi: 10.12701/jyms.2023.01389. Epub 2024 Mar 15.
Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation.
Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW264.7 cells.
DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages.
Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.
非酒精性脂肪性肝病（NAFLD）的特征是肝脏甘油三酯含量增加，且通过肝脏中的C-C基序趋化因子受体（CCR）5途径导致炎性巨噬细胞浸润增加。DA-6034（7-羧甲基氧基-3'，4'，5-三甲氧基黄酮）是灯盏乙素的合成衍生物，在炎症性肠病中表现出抗炎活性。然而，DA-6034对NAFLD炎症反应的影响尚未得到充分阐明。因此，我们旨在确定DA-6034对肝脏脂肪变性和炎症的影响。
将40只雄性C57BL/6J小鼠分为以下四组：（1）正常饮食（RD）组，（2）正常饮食+DA-6034组，（3）高脂饮食（HFD）组，（4）高脂饮食+DA-6034组。实验开始12周后处死所有小鼠。使用RAW264.7细胞评估DA-6034对巨噬细胞的影响。
DA-6034不仅降低了高脂饮食喂养小鼠的肝脏甘油三酯水平和脂质蓄积，还减少了巨噬细胞浸润和促炎细胞因子。根据荧光激活细胞分选分析，DA-6034降低了高脂饮食喂养小鼠肝脏中的CD8+T细胞比例。DA-6034还降低了高脂饮食喂养小鼠肝脏巨噬细胞的CCR5表达和迁移，并抑制了刺激巨噬细胞迁移的CCR2配体和CCR4配体。
总体而言，DA-6034通过调节巨噬细胞中CCR5的表达减轻肥胖中的肝脏脂肪变性和炎症。
