DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Journal of Yeungnam medical science - 41(2024), 2 vom: 08. Apr., Seite 103-112 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Hong Min [VerfasserIn] |
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| Links: |
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| Themen: |
CCR5 receptor |
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| Anmerkungen: |
Date Revised 09.05.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.12701/jyms.2023.01389 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369761529 |
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| 245 | 1 | 0 | |a DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CCR5 receptor | |
| 650 | 4 | |a DA-6034 | |
| 650 | 4 | |a Fatty liver | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Macrophages | |
| 700 | 1 | |a Kwon, Mi-Hye |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Eun Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Ha, Kyung Bong |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Choon Hee |e verfasserin |4 aut | |
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