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 adjuvantinduced 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 bioconstituents 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.

Magnoflorine Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response via the NF-κB/MAPK Signaling Pathways

“…41 There is a growing number of research papers that have used the network pharmacology to elucidate the mechanism of TCM in treatment of RA. [42][43][44][45] Therefore, in this work, we applied network pharmacology as well as molecular docking to predict and shed light on the potential molecular mechanisms of action of Mag on RA. The results showed that the intersection of Mag targets and RA targets contained 6 genes: ACHE, PXR, PTGS2, PTGS1, RXRA and CA2.…”

Activating Blood Circulation, Anti‐Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling

“…Inflammation is a commonly regulated process of the host defense system in response to infections of tissue damage, harmful stimuli, physical stress, and others. [34,[46][47][48][49][50][51] Commonly, inflammation is closely related to BS, and inflammatory cytokine overexpression is accompanied by blood stasis. [10,52] In this study, LJ prominently reduced the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-8, while notably enhancing the anti-inflammatory cytokine IL-10 level compared with the model group.…”

“…Inflammation is a commonly regulated process of the host defense system in response to infections of tissue damage, harmful stimuli, physical stress, and others [34,46–51] . Commonly, inflammation is closely related to BS, and inflammatory cytokine overexpression is accompanied by blood stasis [10,52] .…”

The efficacy of bone marrow mesenchymal stem cells on rat intestinal immune-function injured by ischemia/reperfusion

“…TNF-α is increased in many pathological conditions, including sepsis, malignancy, heart failure, and chronic inflammatory diseases [ 30 , 31 ]. Increased TNF can be found in the blood and joints of patients with severe rheumatoid arthritis [ 32 ]. The level of TNF-α can directly reflect the degree of intestinal mucosal injury during intestinal I/R injury in rats.…”