Zhao Zibo, Lin Shimin, Liu Tao, Hu Xiao, Qin Shurong, Zhan Fengyun, Ma Jiaqi, Huang Chen, Huang Zhibin, Wang Yifei, Zheng Kai, Zhang Wenqing, Ren Zhe
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
Guangdong Province Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China.
Front Pharmacol. 2024 Jul 18;15:1415352. doi: 10.3389/fphar.2024.1415352. eCollection 2024.
Natural plants are valuable resources for exploring new bioactive compounds. L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from L. with unclear biological activities.
The immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation.
AE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling.
AE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.
天然植物是探索新型生物活性化合物的宝贵资源。[植物名称]是一种传统的中草药，历史上一直用于治疗多种疾病。从[植物名称]中分离提取的活性化合物通常具有免疫调节和抗炎特性。青蒿内酯E（AE）是从[植物名称]中分离提取的一种新型倍半萜内酯，其生物学活性尚不清楚。
通过ELISA、RT-qPCR、免疫荧光和蛋白质免疫印迹分析评估AE对巨噬细胞的免疫调节作用。通过蛋白质免疫印迹分析检测AE对脂多糖（LPS）相关信号通路的影响。在斑马鱼模型中，对幼虫进行卵黄显微注射LPS以建立炎症模型，并通过测定斑马鱼的存活率、心率、卵黄囊水肿大小、中性粒细胞和巨噬细胞浸润情况来评估AE的作用。通过分子对接和动态模拟研究AE与Toll样受体4（TLR4）之间的相互作用。
AE降低了LPS刺激的巨噬细胞中促炎细胞因子（TNF-α和IL-6）、炎症介质iNOS和COX-2的表达和分泌，同时减少了细胞内NO和ROS的产生。此外，AE通过抑制MAPK/JAK/STAT3-NF-κB信号通路协同发挥抗炎作用。此外，AE提高了用LPS处理的斑马鱼胚胎的存活率并减轻了炎症反应。最后，分子动力学结果表明，AE通过Ser127残基与LPS受体TLR4形成稳定复合物，从而完全损害MAPK-NF-κB信号的后续激活。
AE具有显著的抗炎活性，是治疗炎症相关疾病的潜在药物。
