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Eun Soo Lee 1 Article
DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice
Hong Min Kim, Mi-Hye Kwon, Eun Soo Lee, Kyung Bong Ha, Choon Hee Chung
J Yeungnam Med Sci. 2024;41(2):103-112.   Published online March 15, 2024
DOI: https://doi.org/10.12701/jyms.2023.01389
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AbstractAbstract PDF
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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    Mohammad Muzaffar Mir, Jaber Alfaifi, Shahzada Khalid Sohail, Syeda Fatima Rizvi, Md Tanwir Akhtar, Mushabab Ayed Abdullah Alghamdi, Rashid Mir, Javed Iqbal Wani, Zia Ul Sabah, Fahad A. Alhumaydhi, Fahad Alremthi, AbdulElah Al Jarallah AlQahtani, Muffarah
    Journal of Personalized Medicine.2024; 14(7): 743.     CrossRef

JYMS : Journal of Yeungnam Medical Science
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