Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification.
10.19540/j.cnki.cjcmm.20221212.402
- Author:
Zhi-Hao DUAN
1
;
Can JIN
2
;
Ying DENG
2
;
Jin-Lang LIU
3
;
Jie WANG
3
;
Shi-Gang LI
2
;
You ZHOU
3
Author Information
1. Department of Orthopedics,Affiliated Renhe Hospital of China Three Gorges University Yichang 443001,China Sports Medicine Research Institute of China Three Gorges University Yichang 443001,China Clinical Medical Research Center of Yichang Sports Injury and Repair Yichang 443001,China Medical College,China Three Gorges University Yichang 443000,China Three-Level Laboratory for Traditional Chinese Pharmacologic (Tumor) Research,China Three Gorges University Yichang 443000,China.
2. Medical College,China Three Gorges University Yichang 443000,China Three-Level Laboratory for Traditional Chinese Pharmacologic (Tumor) Research,China Three Gorges University Yichang 443000,China.
3. Department of Orthopedics,Affiliated Renhe Hospital of China Three Gorges University Yichang 443001,China Sports Medicine Research Institute of China Three Gorges University Yichang 443001,China Clinical Medical Research Center of Yichang Sports Injury and Repair Yichang 443001,China.
- Publication Type:Journal Article
- Keywords:
Chaenomelis Fructus;
experimental verification;
mechanism of action;
molecular docking;
network pharmacology
- MeSH:
Animals;
Mice;
Network Pharmacology;
Vascular Endothelial Growth Factor A;
Molecular Docking Simulation;
Arthritis, Rheumatoid/genetics*;
Tumor Necrosis Factor-alpha;
NF-kappa B;
Drugs, Chinese Herbal/therapeutic use*;
Medicine, Chinese Traditional
- From:
China Journal of Chinese Materia Medica
2023;48(18):4852-4863
- CountryChina
- Language:Chinese
-
Abstract:
The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
