Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia

Abstract

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibrogenic factors Lum, CIV, CXI and Tgfbi participated in the synovial inflammation, fibrosis and hyperplasia in CIA. Based on KOG function class analysis, the proteins involved in the events of the central dogma was explored. They might be hyperplasia related proteins for most of them are related to the proliferation of cancer. ETD significantly attenuated synovial inflammation, fibrosis and hyperplasia in CIA rats by downregulating these proteins. Several proteins have not been observed in RA so far, such as Tmsb4x, Pura, Nfic, Ruvbl1, Snrpd3, U2af2, Srrm2, Srsf7, Elavl1, Hnrnph1, Wars, Yars, Bzw2, Mcts1, Eif4b, Ctsh, Lamp1, Dpp7, Ptges3, Cdc37 and Septin9, they might be potentials targets for RA. Blood biochemistry tests showed the safety of 7 months use of ETD on rats. In conclusion, present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed.

Natural medicines of targeted rheumatoid arthritis and its action mechanism

“…Clinically, non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of RA are achieved by inhibiting COX to inhibit the expression of PGE2. The selective COX-2 inhibitors are a new class of NSAIDs, such as etodolac ( 186 ) and indomethacin ( 187 ). The synovial tissues and fluids of patients with RA have high levels of MMP-1, MMP-3, MMP-9 and MMP-13, which play a key role in the degradation of connective tissue components in RA cartilage ( 156 , 188 ).…”

Multifunctional IL-Based Hydrogel Modulator for the Synergistic Acceleration of Wound Healing: Optimizing Drug Solubility, Antioxidant, and Anti-Inflammatory Effects

“…ETC blocks the cyclooxygenase enzymes that form prostanoids, thus lowering concentrations of prostaglandins and consequently inhibiting inflammation, pain, and fever. Further, ETC is superior to other NSAIDs because it produces less gastrointestinal toxicity and is not addictive compared with them; thus, it is generally selected as a target drug. , Nevertheless, as an active pharmaceutical ingredient, ETC is actually a solid drug that is insoluble in water and cannot be fully and efficiently absorbed by the body, let alone effectively released into the blood . Owing to the relatively poor water solubility of ETC despite its superiority, the simple modification of its structure to improve its dissolution efficiency is not ideal.…”

The accelerated organ senescence and proteotoxicity in thyrotoxicosis mice

“…And the problem of proteasome degradation might be the downstream problem, the upstream events such as transcription, splicing, and translation were the cause. Proteomics can directly detect the changes of proteins in the processes of gene transcription, RNA splicing, protein translation, and folding, and can more comprehensively understand the molecular changes of each segment in the central rule (Feng et al, 2021). TMT (tandem mass tags) employs multiple isotope tags that react covalently with amino groups of peptides to enable simultaneous qualitative and quantitative analysis of proteins in up to 16 different samples (Nusinow et al, 2020).…”