Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Cornus Officinalis and Paeonia Lactiflora in Rheumatoid Arthritis via Network Pharmacology Analysis.

Qinglin Li,Lichuang Huang,Jida Zhang,Gang Cao,Shaoqi Hu

doi:10.3389/fphar.2021.648037

Abstract

Cornus officinalis Sieb et. Zucc and Paeonia lactiflora Pall. have exhibited favorable therapeutic effects against rheumatoid arthritis (RA), but the specific mechanisms of their active compounds remain unclear. The aim of this study was to comprehensively analyze the therapeutic mechanisms of selected active compounds in Cornus officinalis (loganin, ursolic acid, and morroniside) and Paeonia lactiflora (paeoniflorin and albiflorin) via network pharmacology. The pharmacological properties of the five active compounds were evaluated and their potential target genes were identified by database screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analysis were performed to determine the enriched molecular pathways associated with the active compounds. Using network pharmacology tools, eight genes (IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3) were identified as common targets between RA and the five active compounds. Molecular docking simulation revealed the compound-target relationship between the five active compounds and three selected targets from the eight common ones (LGALS3, STAT3, and VEGFA). The compound-target relationships were subsequently validated via preliminary in vivo experiments in a rat model of collagen-induced arthritis. Rats subjected to collagen-induced arthritis showed increased protein expression of LGALS3, STAT3, and VEGFA in synovial tissues. However, treatment using Cornus officinalis or/and Paeonia lactiflora, as well as their most drug-like active compounds (ursolic acid or/and paeoniflorin, respectively, identified based on pharmacological properties), attenuated the expression of these three targets, as previously predicted. Collectively, network pharmacology allowed the pharmacological and molecular roles of Cornus officinalis and Paeonia lactiflora to be systematically revealed, further establishing them as important candidate drugs in the treatment and management of RA.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly affects the joints and causes pain and stiffness
For a preliminary in vivo experimental validation of the predicted compound-target relationship, we evaluated the expression of LGALS3, STAT3, and VEGFA in a rat model of collagen-induced arthritis (CIA) (Figure 8A)
We found that the active compounds of Cornus officinalis and Paeonia lactiflora included in this study share eight common target genes with rheumatoid arthritis (RA), namely IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease that mainly affects the joints and causes pain and stiffness. Disease-modifying antirheumatic drugs such as hydroxychloroquine and leflunomide may be applied to slow the progression of RA, but the use of these drugs may result in a variety of adverse effects (Deng et al, 2020). Surgery is another method of managing RA that aims to repair or fuse joints and may help in certain situations. The popularity of alternative and complementary medicine has grown substantially in recent years, but its effectiveness remains to be validated

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