J Yeungnam Med Sci.
2024 Apr;41(2):103-112. 10.12701/jyms.2023.01389.
DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice
- Affiliations
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- 1Astrogen Inc., Daegu, Korea
- 2The East Coast Research Institute of Life Science, Gangneung-Wonju National University, Gangneung, Korea
- 3Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- 4Research Institute of Metabolism and Inflammation, Yonsei University Wonju College of Medicine, Wonju, Korea
- 5Department of Clinical Research, Vaccine Center for Assisting Safety & Technology, Hwasun, Korea
- KMID: 2554771
- DOI: http://doi.org/10.12701/jyms.2023.01389
Abstract
- Background
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.
Methods
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.
Results
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.
Conclusion
Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.
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