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      Astilbin from Smilax glabra Roxb. Attenuates Inflammatory Responses in Complete Freund's Adjuvant-Induced Arthritis Rats

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          Abstract

          Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. (with red cross-section) grown in Guizhou Province, China. We accessed its effect and potential mechanism on attenuation of the inflammatory response in CFA-induced AA rats. Our results showed that daily oral administration of astilbin at 5.3 mg/kg reduced joint damage in the hind paw of AA rats. Accordingly, astilbin exhibited remarkable inhibitory effects on TNF- α, IL-1 β, and IL-6 mRNA expression. Significant decrease of serum cytokine levels of TNF- α, IL-1 β, and IL-6 was also observed in astilbin-treated AA rats compared to the vehicle-treated AA rats. The reduced expression of these cytokines was associated with protein activity suppression of three key molecular targets in the pathogenesis of RA, including IKK β, NF- κB p65 subunit, and TLR adaptor MyD88. Furthermore, the therapeutic effects of astilbin on the inhibition of cytokines production as well as the reduction of inflammatory response in AA rats are close to a commonly used antirheumatic drug, leflunomide. Collectively, our data suggest that the action mechanism of astilbin, as an anti-inflammatory agent for RA treatment, is associated with modulating the production of proinflammatory cytokines and inhibiting the expression of key elements in NF- κB signaling pathway mediated by TLR.

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          Most cited references40

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          The role of interleukin 6 in the pathophysiology of rheumatoid arthritis.

          Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the synovial fluid and serum of patients with RA and the level correlates with the disease activity and joint destruction. IL-6 can promote synovitis and joint destruction by stimulating neutrophil migration, osteoclast maturation and vascular endothelial growth factor (VEGF)-stimulated pannus proliferation. IL-6 may also be mediating many of the systematic manifestations of RA including inducing the acute-phase reaction [including C-reactive protein (CRP)], anaemia through hecipidin production, fatigue via the hypothalamic-pituitary-adrenal (HPA) axis) and osteoporosis from its effect on osteoclasts. In addition, IL-6 may contribute to the induction and maintenance of the autoimmune process through B-cell maturation and TH-17 differentiation. All of the above makes IL-6 blockade a desirable therapeutic option in the treatment of RA. Following successful animal studies, a humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown to be an effective treatment in several large phase III clinical trials in RA with rapid and sustained improvement in disease activity, reducing radiographic joint damage and improving physical function.
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            NF-kappaB in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction

            The transcription factor NF-κB has been well recognized as a pivotal regulator of inflammation in rheumatoid arthritis (RA), but recent developments revealed a broad involvement of NF-κB in other aspects of RA pathology, including development of T helper 1 responses, activation, abnormal apoptosis and proliferation of RA fibroblast-like synovial cells, and differentiation and activation of bone resorbing activity of osteoclasts. In agreement with this, studies in animal models of RA have demonstrated the high therapeutic efficacy of specific inhibitors of NF-κB pathway, indicating the feasibility of anti-NF-κB therapy for human disease.
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              The role of toll-like receptors in rheumatoid arthritis.

              An increasing body of data supports the role of the innate immune system in the pathogenesis of rheumatoid arthritis (RA). Toll-like receptors (TLRs) are expressed by cells within the RA joint and various endogenous TLR ligands are present within the inflamed joints of patients with RA. Further, various animal models suggest that TLR signaling is important in the pathogenesis of disease. Overall, the data suggest that activation by endogenous TLR ligands may contribute to the persistent expression of proinflammatory cytokines by macrophages and the joint damage to cartilage and bone that occurs in RA. The data support a potential role for suppression of TLR signaling as a novel therapeutic approach in patients with RA.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2017
                22 August 2017
                : 2017
                : 8246420
                Affiliations
                1School of Pharmacy, Guiyang College of Traditional Chinese Medicine, Guiyang 550002, China
                2Center of Miao Medicine Engineering Technology, Guiyang 550002, China
                3School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China
                4Department of Epidemiology and Environmental Health, The State University of New York, Buffalo, NY, USA
                5School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
                Author notes

                Academic Editor: Subash C. Gupta

                Author information
                http://orcid.org/0000-0003-1090-2609
                http://orcid.org/0000-0001-9048-7606
                Article
                10.1155/2017/8246420
                5585559
                29104606
                b501bff9-7c40-4898-ba6a-d91d4c045191
                Copyright © 2017 Lisha Dong et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 May 2017
                : 22 June 2017
                : 9 July 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81460588
                Award ID: 30960503
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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