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      Chinese Herbal Medicines for Rheumatoid Arthritis: Text-Mining the Classical Literature for Potentially Effective Natural Products

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          Abstract

          Background

          Rheumatoid arthritis (RA) is an autoimmune disease characterized by multijoint swelling, pain, and destruction of the synovial joints. Treatments are available but new therapies are still required. One source of new therapies is natural products, including herbs used in traditional medicines. In China and neighbouring countries, natural products have been used throughout recorded history and are still in use for RA and its symptoms. This study used text-mining of a database of classical Chinese medical books to identify candidates for future clinical and experimental investigations of therapeutics for RA.

          Methods

          The database Encyclopaedia of Traditional Chinese Medicine ( Zhong Hua Yi Dian) includes the full texts of over 1,150 classical books. Eight traditional terms were searched. All citations were assessed for relevance to RA. Results and Conclusions. After removal of duplications, 3,174 citations were considered. After applying the exclusion and inclusion criteria, 548 citations of traditional formulas were included. These derived from 138 books written from 206 CE to 1948. These formulas included 5,018 ingredients (mean, 9 ingredients/formula) comprising 243 different natural products. When these text-mining results were compared to the 18 formulas recommended in a modern Chinese Medicine clinical practice guideline, 44% of the herbal formulas were the same. This suggests considerable continuity in the clinical application of these herbs between classical and modern Chinese medicine practice. Of the 15 herbs most frequently used as ingredients of the classical formulas, all have received research attention, and all have been reported to have anti-inflammatory effects. Two of these 15 herbs have already been developed into new anti-RA therapeutics—sinomenine from Sinomenium acutum (Thunb.) Rehd. & Wils and total glucosides of peony from Paeonia lactiflora Pall. Nevertheless, there remains considerable scope for further research. This text-mining approach was effective in identifying multiple natural product candidates for future research.

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          Counting on natural products for drug design.

          Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.
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            Rheumatoid Arthritis

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              Sinomenine Inhibits the Progression of Rheumatoid Arthritis by Regulating the Secretion of Inflammatory Cytokines and Monocyte/Macrophage Subsets

              Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy associated with articular damage and attendant comorbidities. Even although RA treatment has advanced remarkably over the last decade, a significant proportion of patients still do not achieve sustained remission. The cause of RA is not yet known despite the many potential mechanisms proposed. It has been confirmed that RA is associated with dysregulated immune system and persistent inflammation. Therefore, management of inflammation is always the target of therapy. Sinomenine (SIN) is the prescription drug approved by the Chinese government for RA treatment. A previous study found that SIN was a robust anti-inflammation drug. In this study, we screened the different secretory cytokines using inflammation antibody arrays and qRT-PCR in both LPS-induced and SIN-treated RAW264.7 cells followed by evaluation of the ability of SIN to modulate cytokine secretion in a cell model, collagen-induced arthritis (CIA) mouse model, and RA patients. Several clinical indexes affecting the 28-joint disease activity score (DAS28) were determined before and after SIN treatment. Clinical indexes, inflammatory cytokine secretion, and DAS28 were compared among RA patients treated with either SIN or methotrexate (MTX). To explore the mechanism of SIN anti-inflammatory function, RA-associated monocyte/macrophage subsets were determined using flow cytometry in CIA mouse model and RA patients, both treated with SIN. The results demonstrated that SIN regulated IL-6, GM-CSF, IL-12 p40, IL-1α, TNF-α, IL-1β, KC (CXCL1), Eotaxin-2, IL-10, M-CSF, RANTES, and MCP-1 secretion in vivo and in vitro and reduced RA activity and DAS28 in a clinical setting. Furthermore, SIN attenuated CD11b+F4/80+CD64+ resident macrophages in the synovial tissue, CD11b+Ly6C+CD43+ macrophages in the spleen and draining lymph nodes of CIA mice. The percentage of CD14+CD16+ peripheral blood mononuclear cells was reduced by SIN in RA patients. These data indicated that SIN regulates the secretion of multiple inflammatory cytokines and monocyte/macrophage subsets, thereby suppressing RA progression. Therefore, along with MTX, SIN could be an alternative cost-effective anti-inflammatory agent for treating 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
                2020
                28 April 2020
                28 April 2020
                : 2020
                : 7531967
                Affiliations
                1The Second Clinical College of Guangzhou University of Chinese Medicine, No. 111, Dade Road, Yuexiu District, Guangzhou 510120, China
                2Department of Rheumatology and Immunology, Guangdong Provincial Hospital of Chinese Medicine, No. 55, Neihuanxi Road, Higher Education Mega Center, Guangzhou 510006, China
                3China-Australia International Research Centre for Chinese Medicine, RMIT University, P.O. Box 71, Bundoora, Victoria 3083, Australia
                Author notes

                Academic Editor: Antonella Fioravanti

                Author information
                https://orcid.org/0000-0002-3208-2755
                https://orcid.org/0000-0002-5864-3020
                https://orcid.org/0000-0002-0968-9380
                https://orcid.org/0000-0003-2699-9740
                https://orcid.org/0000-0001-6937-9088
                https://orcid.org/0000-0003-1689-8006
                Article
                10.1155/2020/7531967
                7206865
                32419824
                4e4004e3-85d9-469d-a077-0d4d50133c37
                Copyright © 2020 Xuan Xia 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
                : 14 January 2020
                : 9 March 2020
                Funding
                Funded by: National Key Research and Development Project
                Award ID: 2018YFC1705200
                Award ID: 2018YFC1705203
                Funded by: RMIT University
                Funded by: Guangdong Provincial Academy of Chinese Medical Sciences
                Funded by: Guangdong Provincial Hospital of Chinese Medicine
                Award ID: 2017KT1820
                Award ID: 2016KT1571
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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