Altechromone A Ameliorates Inflammatory Bowel Disease by Inhibiting NF-κB and NLRP3 Pathways

阿替克罗酮A通过抑制NF-κB和NLRP3通路改善炎症性肠病

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Abstract

Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, and antiviral activities. However, there is no study about its anti-inflammatory activity in inflammatory bowel disease (IBD). Here, we assess the anti-inflammatory activity, especially in IBD, and its potential mechanism using the zebrafish model. Our results indicated that Altechromone A has anti-inflammatory activity in a CuSO(4)-, tail-cutting-, and LPS-induced inflammatory model in zebrafish, respectively. In addition, Altechromone A greatly reduced the number of neutrophils, improved intestinal motility and efflux efficiency, alleviated intestinal damage, and reduced reactive oxygen species production in the TNBS-induced IBD zebrafish model. The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response.

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