Analyzing How Zhizi Baipi Decoction Regulates VEGF to Suppress RA Angiogenesis Using Network Pharmacology and Experimental Validation.

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily manifests with symptoms such as heat and toxin. However, the key components and molecular mechanisms of Zhizi Baipi decoction (ZBD) in the treatment of RA are still unclear.

Objectives: The study aimed to explore the mechanism of action of ZBD for treating RA through ingredient analysis, network pharmacology, and experimental validation.

Material and methods: The chemical constituents of ZBD were identified by ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS^E). Additionally, the active ingredients of ZBD treating RA were screened by network pharmacology and using molecular docking to verify the binding energy of the active ingredients and ZBD's targets. Then we elucidated ZBD's mechanism of action on collagen-induced arthritis (CIA) model rats. Subsequently, experimental validations were used to validate the findings of network pharmacology.

Results: A total of 84 chemical constituents was identified by UPLC-Q-TOF-MS^E. The results of network pharmacology indicated that ZBD could exert its therapeutic effect on RA through the vascular endothelial growth factor (VEGF) pathway. Molecular docking revealed a strong binding capacity between the target KDR and the active ingredients. Additionally, we quantified the five active ingredients of ZBD. In vivo experiments demonstrated that ZBD inhibited synovial angiogenesis and alleviated the occurrence and progression of RA.

Conclusion: Overall, ZBD has a significant therapeutic effect on RA. The results of qualitative analysis, network pharmacology, molecular docking, and in vivo experiments indicated that the main active components of ZBD could modulate the VEGF pathway to treat RA.