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      Natural medicines of targeted rheumatoid arthritis and its action mechanism

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          Abstract

          Rheumatoid arthritis (RA) is an autoimmune disease involving joints, with clinical manifestations of joint inflammation, bone damage and cartilage destruction, joint dysfunction and deformity, and extra-articular organ damage. As an important source of new drug molecules, natural medicines have many advantages, such as a wide range of biological effects and small toxic and side effects. They have become a hot spot for the vast number of researchers to study various diseases and develop therapeutic drugs. In recent years, the research of natural medicines in the treatment of RA has made remarkable achievements. These natural medicines mainly include flavonoids, polyphenols, alkaloids, glycosides and terpenes. Among them, resveratrol, icariin, epigallocatechin-3-gallate, ginsenoside, sinomenine, paeoniflorin, triptolide and paeoniflorin are star natural medicines for the treatment of RA. Its mechanism of treating RA mainly involves these aspects: anti-inflammation, anti-oxidation, immune regulation, pro-apoptosis, inhibition of angiogenesis, inhibition of osteoclastogenesis, inhibition of fibroblast-like synovial cell proliferation, migration and invasion. This review summarizes natural medicines with potential therapeutic effects on RA and briefly discusses their mechanisms of action against RA.

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          Mechanisms of NF-κB p65 and strategies for therapeutic manipulation

          The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, and Rel-B proteins, which form homo- or heterodimers and remain as an inactive complex with the inhibitory molecules called IκB proteins in resting cells. Two distinct NF-κB signaling pathways have been described: 1) the canonical pathway primarily activated by pathogens and inflammatory mediators, and 2) the noncanonical pathway mostly activated by developmental cues. The most abundant form of NF-κB activated by pathologic stimuli via the canonical pathway is the p65:p50 heterodimer. Disproportionate increase in activated p65 and subsequent transactivation of effector molecules is integral to the pathogenesis of many chronic diseases such as the rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even neurodegenerative pathologies. Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB p65 in the context of chronic inflammation.
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            Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

            Rheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.
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              Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis

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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                01 August 2022
                2022
                : 13
                : 945129
                Affiliations
                [1] 1 School of Medicine, Jiangsu University , Zhenjiang, China
                [2] 2 Chinese Academy of Chinese Medical Sciences , Beijing, China
                [3] 3 Department of Traditional Chinese Medicine, Affiliated Hospital of Jiangsu University , Zhenjiang City, China
                Author notes

                Edited by: Laijun Lai, University of Connecticut, United States

                Reviewed by: Yuhua Fan, Harbin Medical University, China; Jingyu Chen, Anhui Medical University, China

                *Correspondence: Qi Guo, guoqi608@ 123456ujs.edu.cn

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.945129
                9376257
                35979373
                4a9cd29e-ff84-47c7-9f24-bc2dd1eaeb5f
                Copyright © 2022 Liu, Wang, Qian, Tao, Zhang, Hu, Mao and Guo

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 May 2022
                : 11 July 2022
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 235, Pages: 19, Words: 10509
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81803991, 81904166
                Funded by: Natural Science Foundation of Jiangsu Province , doi 10.13039/501100004608;
                Award ID: BK20130543
                Categories
                Immunology
                Review

                Immunology
                rheumatoid arthritis,autoimmune disease,flavonoids,polyphenols,alkaloids,glycosides,terpenes,natural medicines

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