The mechanism of modified Gan Cao Fu Zi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and experimental validation
10.16438/j.0513-4870.2023-0052
- VernacularTitle:基于网络药理学探究加味甘草附子汤治疗类风湿关节炎的作用机制
- Author:
Tian-yu WU
1
;
Ming ZHANG
2
;
Xiao-yu HE
3
;
Yan ZHANG
4
;
Tian XIA
4
;
Yi-qing YANG
4
;
Cheng-zhi TANG
1
;
Yong-jie CHEN
1
;
Zi-xia DING
4
;
Li-qiu CHEN
5
;
Xiao-nan ZHANG
2
Author Information
1. School of Public Health, Bengbu Medical College, Bengbu 233030, China
2. Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Bengbu Medical College, Bengbu 233030, China
3. The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
4. Clinical Medicine Department of Bengbu Medical College, Bengbu 233030, China
5. The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233040, China
- Publication Type:Research Article
- Keywords:
modified Gan Cao Fu Zi Decoction;
rheumatoid arthritis;
network pharmacology;
molecular docking;
collagen-induced arthritis rat
- From:
Acta Pharmaceutica Sinica
2023;58(6):1441-1451
- CountryChina
- Language:Chinese
-
Abstract:
We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.
