Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

Publication date: Available online 20 July 2019Source: Pharmacological ResearchAuthor(s): Jiasi Wu, Yu Luo, Qing Jiang, Sheng Li, Wenge Huang, Li Xiang, Deming Liu, Yingfan Hu, Ping Wang, Xiaoxia Lu, Guolin Zhang, Fei Wang, Xianli MengAbstractInflammasome mediates the activation of caspase-1, which promotes the secretion of proinflammatory cytokines. In this work, we aimed to investigate whether natural compounds from a Traditional Chinese Medicine prescription called San-Huang-Xie-Xin-Tang exert its clinical efficacy by inhibiting inflammasome activation and the underlying mechanism. The inhibitory effects of compounds on caspase-1 were evaluated in recombinant expressed caspase-1 protein and macrophages. Molecular docking was conducted to examine the interaction between compounds and caspase-1. The effects of the compounds on pro-inflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mechanism of the compounds on nucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome activation was investigated in macrophages. The anti-inflammasome effects of compounds were examined in mice stimulated by lipopolysaccharide (LPS) and monosodium urate crystal (MSU). Coptisine was the most potent inhibitor of caspase-1 in the San-Huang-Xie-Xin-Tang prescription. Coptisine adopted a favorable conformation at the active site of caspase-1. Coptisine significantly attenuated mature interleukin (IL)-1β secretion in RAW264.7 macrophages stim...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research

Related Links:

Abstract Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by the arthritis of unknown origin and IL6 is a known target for JIA. 20 known inhibitors towards IL-6 were screened and Methotrexate (MTX) having PubChem ID: 126941 showed high binding capacity with the receptor IL-6. The similarity searching with this compound gave 269 virtual screened compounds. The said screening presented 269 possible drugs having structural similarity to Methotrexate. The docking studies of the screened drugs separated the compound having PubChem CID: 122677576 (re-rank value of -140.262). Toxicity and inte...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Abstract Multiple cytokines play a pivotal role in the pathogenesis of Rheumatoid Arthritis by inducing intracellular signaling and it is known that the members of the Janus kinase (JAK) family are essential for such signal transduction. Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Drugs targeting JAK3 in the treatment of Rheumatoid arthritis is relevant. Therefore, it is of interest to design suitable inhibitors for JAK3 dimer using molecular docking with Molegro Virtual Docker. The compound possessing the highest affinity score is subjected to virtual screening to retrieve inh...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Publication date: Available online 22 August 2019Source: Journal of Clinical NeuroscienceAuthor(s): Bruno Kusznir Vitturi, Bruno Azeredo Coutinho Nascimento, Beatriz Rizkallah Alves, Felipe Sobolewski Carneiro de Campos, Dawton Yukito TorigoeAbstractBackgroundNeurological manifestations of Rheumatoid Arthritis (RA) are usually uncommon. However, a number of recent studies have reported that the burden of cognitive impairment in RA could be significant. We sought to explore the prevalence and clinical predictors of cognitive impairment in persons with RA.MethodsThis is a cross-sectional case-control study with patients with...
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
This study explored the role of central sensitization (CS) pain in patients with various rheumatic diseases using the CS inventory (CSI).MethodsA total of 193 patients of mean age 50.72  ± 9.65 years were included; they were divided into four different groups in terms of their rheumatic diseases. Patients with rheumatoid arthritis (RA), spondyloarthropathy (SpA), osteoarthritis (OA), and fibromyalgia syndrome (FMS) were evaluated in tertiary care rheumatology/pain medicine se ttings. Disease duration and activity, the Bath Ankylosing Spondylitis Disease Activity Index, the Disease Activity Score-2...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Abstract OBJECTIVES: Evaluate the relationship between arthritis diagnosis in those over 50 and exposure to extreme air pollution in utero or infancy (
Source: Environmental Pollution - Category: Environmental Health Authors: Tags: Environ Pollut Source Type: research
Publication date: Available online 22 August 2019Source: Life SciencesAuthor(s): Mehana E. El-Sayed, Khafaga F. Asmaa, El-Blehi S. SamarAbstractExtensive degeneration of articular cartilage (AC) is a primary event in the pathogenesis of osteoarthritis (OA) and other types of joint and bone inflammation. OA results in the loss of joint function, usually accompanied by severe pain, and are the most common type of arthritis, affecting more than 10% of adults. The characteristic signs of OA are progressive cartilage destruction and, eventually, complete loss of chondrocytes. A key enzyme responsible for these degenerative chan...
Source: Life Sciences - Category: Biology Source Type: research
Findings show a dose - or frequency - dependent association; all antibiotic classes linked to higher odds for RA
Source: Pulmonary Medicine News - Doctors Lounge - Category: Respiratory Medicine Tags: Family Medicine, Infections, Internal Medicine, Pharmacy, Pulmonology, Rheumatology, Journal, Source Type: news
ConclusionGEN inhibits IL-6–induced VEGF expression and angiogenesis partially through the JAK2/STAT3 pathway in RA, which has provided a novel insight into the antiangiogenic activity of GEN in RA.The translational potential of this articleOur study provides scientific guidance for the clinical translational research of GEN in the RA treatment.
Source: Journal of Orthopaedic Translation - Category: Orthopaedics Source Type: research
FRIDAY, Aug. 23, 2019 -- Antibiotic prescriptions are associated with a higher risk of rheumatoid arthritis (RA), according to a study published online Aug. 7 in BMC Medicine. Alyshah Abdul Sultan, Ph.D., from Keele University in the United Kingdom,...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
Authors: Strand V, Shah R, Atzinger C, Zhou J, Clewell J, Ganguli A, Tundia N Abstract Objective: Determine healthcare resource utilization (HCRU) and associated costs associated with fatigue and stiffness among patients with rheumatoid arthritis (RA). Methods: A retrospective claims analysis compared RA patients with fatigue or stiffness to matched RA control patients with neither. Claims from a large U.S. commercial insurance database identified new cases of stiffness/fatigue among newly diagnosed patients. Study patients had ≥2 medical claims for RA ≥45 days apart, continuous insurance coverage ≥12 mont...
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
More News: Arthritis | China Health | Drugs & Pharmacology | Men | Rheumatology