痰热清注射液通过调控 NF-κB-ICAM-1/VCAM-1 轴发挥抗登革热作用。

Tanreqing injection demonstrates anti-dengue activity through the regulation of the NF-κB-ICAM-1/VCAM-1 axis.

机构信息

Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.

Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China.

出版信息

Phytomedicine. 2024 Jul 25;130:155764. doi: 10.1016/j.phymed.2024.155764. Epub 2024 May 19.

DOI:10.1016/j.phymed.2024.155764

PMID:38797030

Abstract

BACKGROUND

Tanreqing injection (TRQ) has been employed in clinical practice as a treatment for dengue fever (DF). Nevertheless, the precise pharmacological mechanism underlying its efficacy remains elusive.

METHOD

Network pharmacology, molecular docking, transcriptome sequencing, and experimental evaluation were employed to analyze and study the inhibitory potential of TRQ against dengue virus (DENV).

RESULT

We found that TRQ inhibited the replication of DENV in human umbilical vein endothelial cells, Huh-7 cells, and Hep3B cells. In addition, TRQ prolonged the survival duration of AG129 mice infected with DF, decreased the viral load in serum and organs, and alleviated organ damage. Subsequently, ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of TRQ was performed to identify 314 targets associated with 36 active compounds present in TRQ. Integration of multiple databases yielded 47 DF-related genes. Then, 15 hub targets of TRQ in DF were determined by calculating the network topology parameters (Degree). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these pathways were primarily enriched in the processes of cytokine activation and leukocyte cross-endothelial migration, with significant enrichment of cell adhesion molecules. Molecular docking revealed favorable binding affinity between TRQ's key active compounds and the predicted hub targets. Transcriptome sequencing results showed TRQ's ability to restore the expression of vascular cell adhesion molecule-1 (VCAM-1) post-DENV infection. Finally, TRQ was found to modulate the immune status by regulating the nuclear factor kappa-B (NF-κB)- intercellular cell adhesion molecule-1 (ICAM-1)/VCAM-1 axis, as well as reduce immune cell alterations, inflammatory factor secretion, vascular permeability, and bleeding tendencies induced by DENV infection.

CONCLUSION

Our research suggests that TRQ exerts therapeutic effects on DF by regulating the NF-κB-ICAM-1/VCAM-1 axis.

摘要

背景

痰热清注射液（TRQ）已在临床上用于治疗登革热（DF）。然而，其确切的药理机制仍不清楚。

方法

采用网络药理学、分子对接、转录组测序和实验评价方法分析和研究 TRQ 对登革热病毒（DENV）的抑制潜力。

结果

我们发现 TRQ 抑制 DENV 在人脐静脉内皮细胞、Huh-7 细胞和 Hep3B 细胞中的复制。此外，TRQ 延长了感染 DF 的 AG129 小鼠的存活时间，降低了血清和器官中的病毒载量，并减轻了器官损伤。随后，对 TRQ 进行超高效液相色谱-串联质谱分析，鉴定出与 TRQ 中 36 种活性化合物相关的 314 个靶标。整合多个数据库得到 47 个与 DF 相关的基因。然后，通过计算网络拓扑参数（Degree）确定 TRQ 治疗 DF 的 15 个关键靶标。GO 和京都基因与基因组百科全书分析显示，这些途径主要富集在细胞因子激活和白细胞穿过内皮迁移的过程中，细胞粘附分子显著富集。分子对接显示 TRQ 的关键活性化合物与预测的关键靶标之间具有良好的结合亲和力。转录组测序结果表明 TRQ 能够恢复 DENV 感染后血管细胞粘附分子-1（VCAM-1）的表达。最后，TRQ 通过调节核因子-κB（NF-κB）-细胞间粘附分子-1（ICAM-1）/VCAM-1 轴来调节免疫状态，减少 DENV 感染引起的免疫细胞改变、炎症因子分泌、血管通透性和出血倾向。