Revealing the Active Constituents and Mechanisms of Semiliquidambar cathayensis Chang Roots against Rheumatoid Arthritis through Network Pharmacology, Molecular Docking, and in Vivo Experiment.

Abstract

Semiliquidambar cathayensis Chang roots (SC) are traditional Chinese medicine for treating rheumatoid arthritis (RA). However, the effect and potential mechanism of SC remain unclear. This study aims to reveal the anti-RA constituents and mechanisms of SC based on network pharmacology, molecular docking, and adjuvant-induced arthritis (AIA) model rat experiment. In this work, 9 potential active constituents, including kaempferol, quercetin, naringenin, paeoniflorin, catechin, fraxin, gentianin, hesperetin, and ellagic acid 3,3',4-trimethyl ether, in SC crossed 65 target genes of RA. In addition, 28 core targets were enriched in inflammation and others, among which interleukin-17 (IL-17) and tumor necrosis factor (TNF) were the major targets. The binding of bio-constituents with IL-17 and TNF were performed using molecular docking. Rat experiment demonstrated that the extract of SC restored body weight loss, reduced arthritis score and the indices of thymus and spleen, alleviated ankle joint histopathology, decreased the levels of rheumatoid factor (RF), C-reactive protein (CRP), IL-17, TNF-α, IL-1β, IL-6, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and matrix metalloproteinase-2 (MMP-2), whereas elevated the levels of IL-4 and IL-10. Collectively, it was the first time to comprehensively reveal the anti-RA efficacy and mechanism of SC via suppressing the inflammatory pathway based on network pharmacology, molecular docking, and experimental verification, which provide chemical and pharmacological evidences for the clinical application of SC.