炎症性肠病（IBD）的治疗方法多种多样，但疗效有限，因此迫切需要找到更好的治疗方法。控制粘膜炎症是 IBD 药物治疗的必须条件。抗肿瘤坏死因子α（TNF-α）单克隆抗体的出现，提供了更安全、更有效的治疗方法。然而，这种治疗仍然面临着失去反应的失败。 β-咔啉生物碱具有抗炎药理活性。虽然 Kumujan B 含有 β-咔啉，但其生物活性仍然未知。在本研究中，我们尝试使用 TNF-α 诱导的体外炎症和 DSS 诱导的体内小鼠 IBD 模型来确定 Kumujan B 的抗炎作用。我们的数据显示 Kumujan B 减弱了小鼠腹膜巨噬细胞中由 TNF-α 诱导的白细胞介素 1β (IL-1β) 和白细胞介素 6 (IL-6) 的表达。 Kumujan B 抑制 c-Jun N 末端蛋白激酶 (JNK) 信号传导，尤其是 c-Jun，以实现抗炎反应。此外，Kumujan B 通过蛋白酶体途径促进 K11 连接的泛素化和 c-Jun 的降解。在一项体内研究中，Kumujan B 抑制葡聚糖硫酸钠 (DSS) 诱导的实验小鼠结肠炎中 IL-1β、IL-6 和 TNF-α 的表达，并改善结肠屏障功能。 Kumujan B 表现出体内和体外抗炎作用，使其成为治疗 IBD 的潜在治疗候选药物。版权所有 © 2024 Li, Di, Li, Zhao, Wu, Shaw, Tang, Huang, Chen, Chen, Gau, Gau,萧、陈。

Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.Copyright © 2024 Li, Di, Li, Zhao, Wu, Xiao, Tang, Huang, Chen, Chen, Gao, Gao, Xiao and Chen.