Huang Jing, Li Lei, Xu Liyan, Feng Lixin, Wang Yuxin, Sik Attila Gabor, Jin Meng, Wang Rongchun, Liu Kechun, Li Xiaobin
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan 250103, China.
Mar Drugs. 2025 Jan 19;23(1):47. doi: 10.3390/md23010047.
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, 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 , , , , , , , , , , , , , , and , and promoting the mRNA expression of , and In conclusion, these findings indicate that MBD could be a potential candidate for the treatment of IBD.
炎症性肠病(IBD)的特征是胃肠道中不受控制的慢性复发性炎症,已成为一个全球性的医疗保健问题。在此,我们旨在利用斑马鱼模型阐明源自海洋生物的化合物3-溴-4,5-二羟基苯甲酸甲酯(MBD)的抗炎活性及其潜在机制,尤其是在IBD中的作用。结果表明,MBD可抑制硫酸铜、尾鳍截肢和脂多糖在斑马鱼中诱导的炎症反应。此外,在三硝基苯磺酸(TNBS)诱导的斑马鱼IBD模型中,MBD显著抑制免疫细胞的肠道迁移,增强肠道黏膜屏障的完整性并改善肠道蠕动功能。此外,MBD可抑制TNBS诱导的活性氧升高。进行了网络药理学分析、分子对接、转录组测序和逆转录聚合酶链反应以研究潜在机制。结果表明,MBD可通过抑制 、 、 、 、 、 、 、 、 、 、 、 、 、 和 的mRNA表达,并促进 、 和 的mRNA表达来调节TLR/NF-κB信号通路。总之,这些发现表明MBD可能是治疗IBD的潜在候选药物。