Journal of Yeungnam Medical Science

Yeungnam University College of Medicine, Yeungnam University Institute Medical Science (영남대 의대 학술지 편집위원회)
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DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice

  • Hong Min Kim (Astrogen Inc.) ;
  • Mi-Hye Kwon (The East Coast Research Institute of Life Science, Gangneung-Wonju National University) ;
  • Eun Soo Lee (Department of Internal Medicine, Yonsei University Wonju College of Medicine) ;
  • Kyung Bong Ha (Department of Clinical Research, Vaccine Center for Assisting Safety & Technology) ;
  • Choon Hee Chung (Department of Internal Medicine, Yonsei University Wonju College of Medicine)
  • Received : 2023.12.14
  • Accepted : 2024.02.09
  • Published : 2024.04.30
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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 RAW 264.7 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.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Program of the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2021R1A2B5B01002354) and Ministry of Education (NRF-2019R1I1A1A01042030).

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