ReferenceID 4565
Arctigenin disrupts NLRP3 inflammasome assembly in colonic macrophages via downregulating fatty acid oxidation to prevent colitis-associated cancer
Cancer Lett
Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associ
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Record Fields
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- Reference Id
- 4565
- Evidence Id
- 21155
- Core Evidence Id
- 21155
- Source Reference Id
- 2402
- Herb2 Reference Id
- HBREF003199
- Subject Paper Key
- HBIN016609_32861708
- Pubmed Id
- 32861708
- Doi
- 10.1016/j.canlet.2020.08.033
- Paper Title
- Arctigenin disrupts NLRP3 inflammasome assembly in colonic macrophages via downregulating fatty acid oxidation to prevent colitis-associated cancer
- Paper Abstract
- Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associated cancer (CAC) and explore its mechanisms. Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mice. Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation (FAO) metabolism in macrophages, as determined by untargeted metabolomics. Arctigenin also inhibited the expression of carnitine palmitoyltransferase 1 (CPT1), reduced the acetylation of alpha-tubulin, and disrupted NLRP3 complex formation, which in turn inactivated the NLRP3 inflammasome. Downregulation of the CPT1-FAO-acetyl-coenzyme A (acetyl-CoA)-acetylated alpha-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly, as confirmed by CPT1 overexpression. Lastly, arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice, and the effect was significantly diminished by the overexpression of adeno-associated virus (AAV)9-CPT1. Taken together, these results show that the inhibition of NLRP3 inflammasome assembly in macrophages due to FAO downregulation contributes to the preventative effect of arctigenin against CAC. Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis.
- Journal
- Cancer Lett
- Publish Year
- 2020
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal Experiment
- Phenotype Related
- Colon Carcinogenesis; Colitis-associated Cancer; Colitis; Tumors
- Paper Title Cn
- Paper Title En
- Arctigenin disrupts NLRP3 inflammasome assembly in colonic macrophages via downregulating fatty acid oxidation to prevent colitis-associated cancer
- Bilingual Status
- semi_complete