PMID- 36552612 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221225 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 11 IP - 12 DP - 2022 Dec 4 TI - Broccoli-Derived Glucoraphanin Activates AMPK/PGC1alpha/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice. LID - 10.3390/antiox11122404 [doi] LID - 2404 AB - 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)-1beta, IL-18, and tumor necrosis factor-alpha (TNF-alpha), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, 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. FAU - Tian, Qiyu AU - Tian Q AD - School of Food Science, Washington State University, Pullman, WA 99164, USA. AD - Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA. FAU - Xu, Zhixin AU - Xu Z AD - School of Food Science, Washington State University, Pullman, WA 99164, USA. FAU - Sun, Qi AU - Sun Q AUID- ORCID: 0000-0002-5434-1324 AD - School of Food Science, Washington State University, Pullman, WA 99164, USA. FAU - Iniguez, Alejandro Bravo AU - Iniguez AB AD - School of Food Science, Washington State University, Pullman, WA 99164, USA. FAU - Du, Min AU - Du M AD - Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA. FAU - Zhu, Mei-Jun AU - Zhu MJ AD - School of Food Science, Washington State University, Pullman, WA 99164, USA. LA - eng GR - 2018-67017-27517/USDA-National Institute of Food and Agriculture (USDA-NIFA)/ PT - Journal Article DEP - 20221204 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC9774969 OTO - NOTNLM OT - DSS OT - NRF2 OT - glucoraphanin OT - inflammatory bowel diseases OT - mitochondrial homeostasis OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2022/12/24 06:00 MHDA- 2022/12/24 06:01 PMCR- 2022/12/04 CRDT- 2022/12/23 01:16 PHST- 2022/11/04 00:00 [received] PHST- 2022/11/30 00:00 [revised] PHST- 2022/12/01 00:00 [accepted] PHST- 2022/12/23 01:16 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/24 06:01 [medline] PHST- 2022/12/04 00:00 [pmc-release] AID - antiox11122404 [pii] AID - antioxidants-11-02404 [pii] AID - 10.3390/antiox11122404 [doi] PST - epublish SO - Antioxidants (Basel). 2022 Dec 4;11(12):2404. doi: 10.3390/antiox11122404.