A Preliminary Inquiry Into the Potential Mechanism of Huang-Lian-Jie-Du Decoction in Treating Rheumatoid Arthritis via Network Pharmacology and Molecular Docking.

Jingjing Pan,Zhenlin Jin,Xupeng Chen,Chang Xu,Chenlu Li

doi:10.3389/fcell.2021.740266

Abstract

Huang-Lian-Jie-Du decoction (HLJDD) has been widely applied to treat inflammation-associated diseases for thousands of years in China. However, the concrete molecular mechanism of HLJDD in the treatment of rheumatoid arthritis (RA) remains unclear. In this work, network pharmacology and molecular docking were applied to preliminarily analyze the potential active ingredients, drug targets, and related pathways of HLJDD on treating RA. A total of 102 active compounds with corresponding 189 targets were identified from HLJDD, and 41 common targets were further identified by intersecting with RA-related targets. Functional enrichment analysis was performed to screen the biological pathways associated with RA. Ten hub targets were further identified through constructing the protein–protein interaction (PPI) network of common targets, which were mainly enriched in the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway. Furthermore, a complex botanical drugs-ingredients-hub-targets-disease network was successfully constructed. The molecular docking results exhibited that these vital ingredients of HLJDD had a stable binding to the hub targets. Among these ingredients, quercetin (MOL000098) was the most common molecule with stable binding to all the targets, and PTGS2 was considered the most important target with multiple regulations by the most active ingredients. In vitro, we successfully validated the inhibitory role of quercetin in the cellular proliferation of human RA fibroblast-like synoviocyte cell line (MH7A cells). These findings indicated that the potential mechanisms of HLJDD for RA treatment might be attributed to inhibiting the immune-inflammatory response, reducing the release of chemokines, and alleviating the destruction of extracellular matrix (ECM) in the synovial compartment.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, pannus formation, and cartilage erosion, eventually leading to progressive joint dysfunction, deformity, and increased mortality risk (Smolen et al, 2016)
Huang-Lian-Jie-Du decoction (HLJDD) has been widely applied to the treatment of inflammationassociated diseases including hepatitis (Wei et al, 2016), pneumonia (Li et al, 2021), Alzheimer’s disease (AD) (Gu et al, 2018), inflammatory bowel disease (IBD) (Yuan et al, 2019), and rheumatoid arthritis (RA) (Hu et al, 2013)
During the period of COVID19, HLJDD was found to play a therapeutic role in COVID-19 through regulating multiple signaling pathways based on targeting genes such as IL6, IL10, Matrix metalloproteinase-9 (MMP9), NOS2, VEGF, and TGFβ1 (Liu et al, 2021)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, pannus formation, and cartilage erosion, eventually leading to progressive joint dysfunction, deformity, and increased mortality risk (Smolen et al, 2016). The treatment of RA was mainly dependent on the appropriate combination of physical, pharmacological, and surgical approaches, of which nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) were widely used to lighten inflammation and improve joint function (Wilsdon and Hill, 2017; Conigliaro et al, 2019). These drugs may result in some adverse effects, including infection, gastrotract reaction, skin rashes, bone marrow suppression, and liver and kidney toxicity (Chen et al, 2019). The concrete molecular mechanism of HLJDD in the treatment of RA was still unclear

Methods

Discussion

Conclusion