Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4
Inflammation, an innate immune response mediated by macrophages, has been a hallmark leading to the pathophysiology of diseases. In this study, we examined the inhibitory effects of ginsenoside compound K (CK) on lipopolysaccharide (LPS)-induced inflammation and metabolic alteration in RAW 264.7 mac...
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MDPI AG
2023-03-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/7/1626 |
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| author | Hyunju Kang Shin Kim Jin-Young Lee Bohkyung Kim |
| author_facet | Hyunju Kang Shin Kim Jin-Young Lee Bohkyung Kim |
| author_sort | Hyunju Kang |
| collection | DOAJ |
| description | Inflammation, an innate immune response mediated by macrophages, has been a hallmark leading to the pathophysiology of diseases. In this study, we examined the inhibitory effects of ginsenoside compound K (CK) on lipopolysaccharide (LPS)-induced inflammation and metabolic alteration in RAW 264.7 macrophages by regulating sirtuin 1 (SIRT1) and histone deacetylase 4 (HDAC4). LPS suppressed SIRT1 while promoting HDAC4 expression, accompanied by increases in cellular reactive oxygen species accumulation and pro-inflammatory gene expression; however, the addition of CK elicited the opposite effects. CK ameliorated the LPS-induced increase in glycolytic genes and abrogated the LPS-altered genes engaged in the NAD+ salvage pathway. LPS decreased basal, maximal, and non-mitochondrial respiration, reducing ATP production and proton leak in macrophages, which were abolished by CK. SIRT1 inhibition augmented <i>Hdac4</i> expression along with increased LPS-induced inflammatory and glycolytic gene expression, while decreasing genes that regulate mitochondrial biogenesis; however, its activation resulted in the opposite effects. Inhibition of HDAC4 enhanced <i>Sirt1</i> expression and attenuated the LPS-induced inflammatory gene expression. In conclusion, CK exerted anti-inflammatory and antioxidant properties with the potential to counteract the alterations of energy metabolism, including glycolysis and mitochondrial respiration, through activating SIRT1 and repressing HDAC4 in LPS-stimulated macrophages. |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T05:28:28Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-24b601e6363f4a63b9faa3b11dce9cec2023-11-17T17:19:40ZengMDPI AGNutrients2072-66432023-03-01157162610.3390/nu15071626Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4Hyunju Kang0Shin Kim1Jin-Young Lee2Bohkyung Kim3Department of Food and Nutrition, Keimyung University, Daegu 42601, Republic of KoreaDepartment of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of KoreaDepartment of Biological Sciences, Keimyung University, Daegu 42601, Republic of KoreaDepartment of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of KoreaInflammation, an innate immune response mediated by macrophages, has been a hallmark leading to the pathophysiology of diseases. In this study, we examined the inhibitory effects of ginsenoside compound K (CK) on lipopolysaccharide (LPS)-induced inflammation and metabolic alteration in RAW 264.7 macrophages by regulating sirtuin 1 (SIRT1) and histone deacetylase 4 (HDAC4). LPS suppressed SIRT1 while promoting HDAC4 expression, accompanied by increases in cellular reactive oxygen species accumulation and pro-inflammatory gene expression; however, the addition of CK elicited the opposite effects. CK ameliorated the LPS-induced increase in glycolytic genes and abrogated the LPS-altered genes engaged in the NAD+ salvage pathway. LPS decreased basal, maximal, and non-mitochondrial respiration, reducing ATP production and proton leak in macrophages, which were abolished by CK. SIRT1 inhibition augmented <i>Hdac4</i> expression along with increased LPS-induced inflammatory and glycolytic gene expression, while decreasing genes that regulate mitochondrial biogenesis; however, its activation resulted in the opposite effects. Inhibition of HDAC4 enhanced <i>Sirt1</i> expression and attenuated the LPS-induced inflammatory gene expression. In conclusion, CK exerted anti-inflammatory and antioxidant properties with the potential to counteract the alterations of energy metabolism, including glycolysis and mitochondrial respiration, through activating SIRT1 and repressing HDAC4 in LPS-stimulated macrophages.https://www.mdpi.com/2072-6643/15/7/1626ginsenoside compound Kmacrophageinflammationsirtuin 1histone deacetylase 4 |
| spellingShingle | Hyunju Kang Shin Kim Jin-Young Lee Bohkyung Kim Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 Nutrients ginsenoside compound K macrophage inflammation sirtuin 1 histone deacetylase 4 |
| title | Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 |
| title_full | Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 |
| title_fullStr | Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 |
| title_full_unstemmed | Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 |
| title_short | Inhibitory Effects of Ginsenoside Compound K on Lipopolysaccharide-Stimulated Inflammatory Responses in Macrophages by Regulating Sirtuin 1 and Histone Deacetylase 4 |
| title_sort | inhibitory effects of ginsenoside compound k on lipopolysaccharide stimulated inflammatory responses in macrophages by regulating sirtuin 1 and histone deacetylase 4 |
| topic | ginsenoside compound K macrophage inflammation sirtuin 1 histone deacetylase 4 |
| url | https://www.mdpi.com/2072-6643/15/7/1626 |
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