Network Pharmacology and Molecular Docking-Based Prediction of the Mechanism of Qianghuo Shengshi Decoction against Rheumatoid Arthritis.

Zhihao Zeng,Jieyi Jiang,Jiaoting Hu,Huixian Zhong,Guanlin Xiao,Sumei Li,Yangxue Li,Huajing Huang,Ruipei Yang,Xiaoli Bi,Mohammad Hassan Baig

doi:10.1155/2021/6623912

Abstract

Qianghuo Shengshi decoction (QHSSD) is a classical Chinese medicine formula, which is used in clinical practice for the treatment of rheumatoid arthritis (RA) in China. However, the pharmacological mechanism of QHSSD on RA has remained unclear by now. We collected and screened active compounds and its potential targets by the pharmacology platform of Chinese herbal medicines. In addition, the therapeutic targets of RA were obtained and selected from databases. Network construction analyzed that 128 active compounds may act on 87 candidate targets and identified a total of 18 hub targets. GO annotation and KEGG enrichment investigated that the action mechanism underlying the treatment of RA by QHSSD might be involved in cell proliferation, angiogenesis, anti-inflammation, and antioxidation. Finally, molecular docking verification showed that TP53, VEGFA, TNF, EGFR, and NOS3 may be related to the RA treatment and molecular dynamics simulation showed the stability of protein-ligand interactions. In this work, QHSSD might exert therapeutic effect through a multicomponent, multitarget, and multipathway in RA from a holistic aspect, which provides basis for its mechanism of action and subsequent experiments.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease with the following symptoms: tender, warm, swollen, and stiff joints in the morning and as RA progresses, resulting in bone erosion, joint deformity, and physical disabilities [1,2,3,4]
In order to verify the rationality of the docking for the TP53 and quercetin system, we investigated the docking of IRAK4 (PDB ID: 2a9i) and quercetin; the binding affinity of IRAK4-quercetin was −6.6 kcal/mol
The traditional Chinese medicine integrative database (TCMID) and a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-Traditional Chinese medicine (TCM)) database were used to predict the targets of Chinese herbal medicine [27, 28], whereas we found that the results of these databases were different because of the screening criteria

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease with the following symptoms: tender, warm, swollen, and stiff joints in the morning and as RA progresses, resulting in bone erosion, joint deformity, and physical disabilities [1,2,3,4]. The drug treatment of RA mainly focuses on nonsteroidal antiinflammatory drugs (NSAIDs), steroids, disease-modifying antirheumatic drugs (DMARDs), and glucocorticoids. These drugs can only delay the progression of RA, which may increase the risk of infection. There is a rising trend of the application of traditional Chinese medicine in the treatment of RA, and the RA patients are more inclined to choose complementary medicine as a medical treatment [8,9,10]. Traditional Chinese medicine (TCM) has a long history of clinical use in China, used as complementary and alternative medicines in treatment [11]. Qianghuo Shengshi decoction (QHSSD) is a classic clinical prescription from internal and external causes (Nei Wai Shang Bian Huo Lun). QHSSD can dispel wind and dampness and sweat and alleviate pain, consisting of seven herbs: Notopterygii rhizoma et radix (Qianghuo, QH), Angelicae pubescentis radix (Duhuo, DH), Qianghuo shengshi decoction (QHSSD)

Methods

Results

Discussion

Conclusion