Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/1/47 |
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| Summary: | Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine organisms, especially in IBD, using a zebrafish model. The results indicated that MBD could inhibit the inflammatory responses induced by CuSO<sub>4</sub>, tail amputation and LPS in zebrafish. Furthermore, MBD notably inhibited the intestinal migration of immune cells, enhanced the integrity of the gut mucosal barrier and improved intestinal peristalsis function in a zebrafish IBD model induced by trinitro-benzene-sulfonic acid (TNBS). In addition, MBD could inhibit ROS elevation induced by TNBS. Network pharmacology analysis, molecular docking, transcriptomics sequencing and RT-PCR were conducted to investigate the potential mechanism. The results showed that MBD could regulate the TLR/NF-κB pathways by inhibiting the mRNA expression of <i>TNF-α</i>, <i>NF-κB</i>, <i>IL-1</i>, <i>IL-1β</i>, <i>IL6</i>, <i>AP1</i>, <i>IFNγ</i>, <i>IKKβ</i>, <i>MyD88</i>, <i>STAT3</i>, <i>TRAF1</i>, <i>TRAF6</i>, <i>NLRP3</i>, <i>NOD2</i>, <i>TLR3</i> and <i>TLR4</i>, and promoting the mRNA expression of <i>IL4</i>, <i>IκBα</i> and <i>Bcl-2.</i> In conclusion, these findings indicate that MBD could be a potential candidate for the treatment of IBD. |
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| ISSN: | 1660-3397 |