Exploring mechanism of Porana racemosa Roxb. in treating rheumatoid arthritis based on integration of network pharmacology and molecular docking combined with experimental validation
10.16438/j.0513-4870.2024-0759
- VernacularTitle:网络药理学、分子对接结合实验验证探讨飞蛾藤治疗类风湿关节炎的作用机制
- Author:
Chen-yu YE
1
;
Ning LI
2
;
Yin-zi CHEN
1
;
Tong QU
2
;
Jing HU
2
;
Zhi-yong CHEN
2
;
Hui REN
2
Author Information
1. School of Life Sciences, Northwest University, Xi'an
2. Shaanxi Academy of Traditional Chinese Medicine, Xi'an
- Publication Type:Research Article
- Keywords:
rheumatoid arthritis;
italic>Porana racemosa Roxb.;
network pharmacology;
molecular docking;
apoptosis;
MH7A cell
- From:
Acta Pharmaceutica Sinica
2025;60(1):117-129
- CountryChina
- Language:Chinese
-
Abstract:
Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.
