Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice
As the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplemen...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/12/2404 |
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| author | Qiyu Tian Zhixin Xu Qi Sun Alejandro Bravo Iniguez Min Du Mei-Jun Zhu |
| author_facet | Qiyu Tian Zhixin Xu Qi Sun Alejandro Bravo Iniguez Min Du Mei-Jun Zhu |
| author_sort | Qiyu Tian |
| collection | DOAJ |
| description | As the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplementation can prevent mitochondrial dysfunction and oxidative stress in an acute colitis mouse model induced by dextran sulfate sodium (DSS). Eight-week-old mice were fed a regular rodent diet either supplemented with or without GRP. After 4 weeks of dietary treatments, half of the mice within each dietary group were subjected to 2.5% DSS treatment to induce colitis. Dietary GRP decreased DSS-induced body weight loss, disease activity index, and colon shortening. Glucoraphanin supplementation protected the colonic histological structure, suppressed inflammatory cytokines, interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, and nuclear factor erythroid 2-related factor 2 (NRF2) pathways in the colonic tissues of DSS-treated mice, which was associated with increased mitochondrial DNA and decreased content of the oxidative product 8-hydroxydeoxyguanosine (8-OHDG), a nucleotide oxidative product of DNA. In conclusion, dietary GRP attenuated mitochondrial dysfunction, inflammatory response, and oxidative stress induced by DSS, suggesting that dietary GRP provides a dietary strategy to alleviate IBD symptoms. |
| first_indexed | 2024-03-09T17:23:11Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:23:11Z |
| publishDate | 2022-12-01 |
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| series | Antioxidants |
| spelling | doaj.art-962f2957d2c84258b1d036ed3cadcaa72023-11-24T12:57:30ZengMDPI AGAntioxidants2076-39212022-12-011112240410.3390/antiox11122404Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in MiceQiyu Tian0Zhixin Xu1Qi Sun2Alejandro Bravo Iniguez3Min Du4Mei-Jun Zhu5School of Food Science, Washington State University, Pullman, WA 99164, USASchool of Food Science, Washington State University, Pullman, WA 99164, USASchool of Food Science, Washington State University, Pullman, WA 99164, USASchool of Food Science, Washington State University, Pullman, WA 99164, USADepartment of Animal Sciences, Washington State University, Pullman, WA 99164, USASchool of Food Science, Washington State University, Pullman, WA 99164, USAAs the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplementation can prevent mitochondrial dysfunction and oxidative stress in an acute colitis mouse model induced by dextran sulfate sodium (DSS). Eight-week-old mice were fed a regular rodent diet either supplemented with or without GRP. After 4 weeks of dietary treatments, half of the mice within each dietary group were subjected to 2.5% DSS treatment to induce colitis. Dietary GRP decreased DSS-induced body weight loss, disease activity index, and colon shortening. Glucoraphanin supplementation protected the colonic histological structure, suppressed inflammatory cytokines, interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, and nuclear factor erythroid 2-related factor 2 (NRF2) pathways in the colonic tissues of DSS-treated mice, which was associated with increased mitochondrial DNA and decreased content of the oxidative product 8-hydroxydeoxyguanosine (8-OHDG), a nucleotide oxidative product of DNA. In conclusion, dietary GRP attenuated mitochondrial dysfunction, inflammatory response, and oxidative stress induced by DSS, suggesting that dietary GRP provides a dietary strategy to alleviate IBD symptoms.https://www.mdpi.com/2076-3921/11/12/2404glucoraphanininflammatory bowel diseasesDSSNRF2oxidative stressmitochondrial homeostasis |
| spellingShingle | Qiyu Tian Zhixin Xu Qi Sun Alejandro Bravo Iniguez Min Du Mei-Jun Zhu Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice Antioxidants glucoraphanin inflammatory bowel diseases DSS NRF2 oxidative stress mitochondrial homeostasis |
| title | Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice |
| title_full | Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice |
| title_fullStr | Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice |
| title_full_unstemmed | Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice |
| title_short | Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice |
| title_sort | broccoli derived glucoraphanin activates ampk pgc1α nrf2 pathway and ameliorates dextran sulphate sodium induced colitis in mice |
| topic | glucoraphanin inflammatory bowel diseases DSS NRF2 oxidative stress mitochondrial homeostasis |
| url | https://www.mdpi.com/2076-3921/11/12/2404 |
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