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: Jing Huang, Lei Li, Liyan Xu, Lixin Feng, Yuxin Wang, Attila Gabor SIK, Meng Jin, Rongchun Wang, Kechun Liu, Xiaobin Li
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/1/47
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author Jing Huang
Lei Li
Liyan Xu
Lixin Feng
Yuxin Wang
Attila Gabor SIK
Meng Jin
Rongchun Wang
Kechun Liu
Xiaobin Li
author_facet Jing Huang
Lei Li
Liyan Xu
Lixin Feng
Yuxin Wang
Attila Gabor SIK
Meng Jin
Rongchun Wang
Kechun Liu
Xiaobin Li
author_sort Jing Huang
collection DOAJ
description 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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publishDate 2025-01-01
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series Marine Drugs
spelling doaj-art-b8027f9910184c5c8cfe984e9fe8648a2025-01-24T13:39:37ZengMDPI AGMarine Drugs1660-33972025-01-012314710.3390/md23010047Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB PathwaysJing Huang0Lei Li1Liyan Xu2Lixin Feng3Yuxin Wang4Attila Gabor SIK5Meng Jin6Rongchun Wang7Kechun Liu8Xiaobin Li9Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaBiology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, ChinaInflammatory 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.https://www.mdpi.com/1660-3397/23/1/47methyl 3-bromo-4,5-dihydroxybenzoatezebrafishTNBSinflammatory bowel diseaseNF-κB pathway
spellingShingle Jing Huang
Lei Li
Liyan Xu
Lixin Feng
Yuxin Wang
Attila Gabor SIK
Meng Jin
Rongchun Wang
Kechun Liu
Xiaobin Li
Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
Marine Drugs
methyl 3-bromo-4,5-dihydroxybenzoate
zebrafish
TNBS
inflammatory bowel disease
NF-κB pathway
title Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
title_full Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
title_fullStr Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
title_full_unstemmed Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
title_short Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways
title_sort methyl 3 bromo 4 5 dihydroxybenzoate attenuates inflammatory bowel disease by regulating tlr nf κb pathways
topic methyl 3-bromo-4,5-dihydroxybenzoate
zebrafish
TNBS
inflammatory bowel disease
NF-κB pathway
url https://www.mdpi.com/1660-3397/23/1/47
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