Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model
<i>Ribes diacanthum</i> Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by li...
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MDPI AG
2020-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/7/622 |
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| author | Na Yeon Kim Sun Hee Cheong Kun Jong Lee Dai-Eun Sok Mee Ree Kim |
| author_facet | Na Yeon Kim Sun Hee Cheong Kun Jong Lee Dai-Eun Sok Mee Ree Kim |
| author_sort | Na Yeon Kim |
| collection | DOAJ |
| description | <i>Ribes diacanthum</i> Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis in mice. We demonstrated that EARDP protected against LPS-induced cell death by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production, as well as the synthesis of pro-inflammatory mediators and cytokines, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. EARDP inhibited the phosphorylation and degradation of inhibitory κB-α (IκB-α) and the activation of nuclear factor (NF)-κB, indicating that the anti-inflammatory effect of EARDP was mediated via the suppression of NF-κB nuclear translocation. In addition, EARDP induced the heme oxygenase-1 (HO-1) expression and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), indicating that EARDP induced HO-1 via the Nrf2 pathway in RAW 264.7 cells. Furthermore, EARDP significantly suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. However, ZnPP, a specific inhibitor of HO-1, reversed the EARDP-mediated inhibition of NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages. EARDP blocked the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt in LPS-stimulated RAW 264.7 cells. In the in vivo animal model, EARDP significantly and dose-dependently reduced TPA-induced secretion of TNF-α and IL-6 in mouse ear. Based on these results, EARDP represents a promising natural compound, protective against oxidative stress and inflammatory diseases. |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:27:30Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-42450b32729147eabcde3076d907a1b72023-11-20T06:53:00ZengMDPI AGAntioxidants2076-39212020-07-019762210.3390/antiox9070622Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal ModelNa Yeon Kim0Sun Hee Cheong1Kun Jong Lee2Dai-Eun Sok3Mee Ree Kim4Department of Food and Nutrition, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaDepartment of Marine Bio Food Science, College of Fisheries and Ocean Science, Chonnam National University, Yeosu 550-749, KoreaDepartment of Food and Nutrition, Soongui Women’s College, 10 Soparo 2-gil, Joong Gu, Seoul 100-751, KoreaCollege of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, KoreaDepartment of Food and Nutrition, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea<i>Ribes diacanthum</i> Pall (RDP) is a Mongolian traditional medicine used to treat renal inflammation. In the present study, we initially investigated the anti-inflammatory effects and mechanisms of action of ethylacetate extract of RDP (EARDP) in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis in mice. We demonstrated that EARDP protected against LPS-induced cell death by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production, as well as the synthesis of pro-inflammatory mediators and cytokines, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. EARDP inhibited the phosphorylation and degradation of inhibitory κB-α (IκB-α) and the activation of nuclear factor (NF)-κB, indicating that the anti-inflammatory effect of EARDP was mediated via the suppression of NF-κB nuclear translocation. In addition, EARDP induced the heme oxygenase-1 (HO-1) expression and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), indicating that EARDP induced HO-1 via the Nrf2 pathway in RAW 264.7 cells. Furthermore, EARDP significantly suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. However, ZnPP, a specific inhibitor of HO-1, reversed the EARDP-mediated inhibition of NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages. EARDP blocked the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt in LPS-stimulated RAW 264.7 cells. In the in vivo animal model, EARDP significantly and dose-dependently reduced TPA-induced secretion of TNF-α and IL-6 in mouse ear. Based on these results, EARDP represents a promising natural compound, protective against oxidative stress and inflammatory diseases.https://www.mdpi.com/2076-3921/9/7/622anti-inflammationHO-1NF-κBNrf2RAW 264.7 macrophages<i>Ribes diacanthum</i> Pall |
| spellingShingle | Na Yeon Kim Sun Hee Cheong Kun Jong Lee Dai-Eun Sok Mee Ree Kim Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model Antioxidants anti-inflammation HO-1 NF-κB Nrf2 RAW 264.7 macrophages <i>Ribes diacanthum</i> Pall |
| title | Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model |
| title_full | Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model |
| title_fullStr | Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model |
| title_full_unstemmed | Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model |
| title_short | Anti-Inflammatory Effects of <i>Ribes diacanthum</i> Pall Mediated via Regulation of Nrf2/HO-1 and NF-κB Signaling Pathways in LPS-Stimulated RAW 264.7 Macrophages and a TPA-Induced Dermatitis Animal Model |
| title_sort | anti inflammatory effects of i ribes diacanthum i pall mediated via regulation of nrf2 ho 1 and nf κb signaling pathways in lps stimulated raw 264 7 macrophages and a tpa induced dermatitis animal model |
| topic | anti-inflammation HO-1 NF-κB Nrf2 RAW 264.7 macrophages <i>Ribes diacanthum</i> Pall |
| url | https://www.mdpi.com/2076-3921/9/7/622 |
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