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      Qing-Luo-Yin Alleviated Monocytes/Macrophages-Mediated Inflammation in Rats with Adjuvant-Induced Arthritis by Disrupting Their Interaction with (Pre)-Adipocytes Through PPAR-γ Signaling

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          Abstract

          Background

          The Chinese herbal formula Qing-Luo-Yin (QLY) has been successfully used in rheumatoid arthritis treatment for decades. It exhibits notable immune and metabolism regulatory properties. Thereby, we investigated its effects on the interplay between (pre)-adipocytes and monocytes/macrophages under adjuvant-induced arthritis (AIA) circumstances.

          Methods

          Fat reservoir and histological characteristics of white fat tissues (WAT) in AIA rats receiving QLY treatment were examined upon sacrifice. Metabolic parameters, clinical indicators, and oxidative stress levels were determined using corresponding kits, while mRNA/protein expression was investigated by PCR and immunoblotting methods. M1 macrophage distribution in WAT was assessed by flow cytometry. The effects of QLY on (pre)-adipocytes were further validated by experiments in vitro.

          Results

          Compared with normal healthy controls, body weight and circulating triglyceride were declined in AIA rats, but serological levels of free fatty acids and low-density lipoprotein cholesterol were increased. mRNA IL-1β and iNOS expression in white blood cells and rheumatoid factor, C-reactive protein, anti-cyclic citrullinated peptide antibody, MCP-1 and IL-1β production in serum/WAT were up-regulated. Obvious CD86 +CD11b + macrophages were enriched in WAT. Meanwhile, expression of PPAR-γ and SIRT1 and secretion of adiponectin and leptin in these AIA rats were impaired. QLY restored all these pathological changes. Of note, it significantly stimulated PPAR-γ expression in the treated AIA rats. Accordingly, QLY-containing serum promoted SCD-1, PPAR-γ, and SIRT1 expression in pre-adipocytes cultured in vitro. AIA rats-derived peripheral blood mononuclear cells suppressed PPAR-γ and SCD-1 expression in co-cultured pre-adipocytes, but serum from AIA rats receiving QLY treatment did not exhibit this potential. The changes on PPAR-γ expression eventually resulted in varied adipocyte differentiation statuses. PPAR-γ selective inhibitor T0070907 abrogated QLY-induced MCP-1 production decline in LPS-primed pre-adipocytes and reduced adiponectin secretion.

          Conclusion

          QLY was potent in promoting PPAR-γ expression and consequently disrupted inflammatory feedback in WAT by altering monocytes/macrophages polarization and adipocytes differentiation.

          Most cited references32

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          The pathogenesis of rheumatoid arthritis.

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            Inflammation and metabolism in tissue repair and regeneration

            Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue's regenerative capacity and the quality of the inflammatory response, the outcome is generally imperfect, with some degree of fibrosis, which is defined by aberrant accumulation of collagenous connective tissue. Inflammatory cells multitask at the wound site by facilitating wound debridement and producing chemokines, metabolites, and growth factors. If this well-orchestrated response becomes dysregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. Here we review the current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, and briefly discuss where important knowledge gaps remain.
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              Targeting monocytes/macrophages in the treatment of rheumatoid arthritis.

              Biotherapies have revolutionized the treatment of RA. However, much work is needed to understand all the mechanisms of these biotherapies, and alternatives are needed to circumvent adverse effects and the high cost of these long-lasting treatments. In this article we outline some of the approaches we have used to target monocytes/macrophages as major components of inflammation and bone homeostasis. We also discuss how anti-TNF-α antibodies target monocytes/macrophages in the complex mechanisms contributing to inhibition of inflammation.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                16 July 2021
                2021
                : 15
                : 3105-3118
                Affiliations
                [1 ]Department of Traditional Chinese Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) , Wuhu, 241000, People’s Republic of China
                [2 ]Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College , Wuhu, 241000, People’s Republic of China
                [3 ]Faculty of Traditional Thai Medicine, Prince of Songkla University , Hat Yai, 90112, Thailand
                [4 ]Department of Pharmacy, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) , Wuhu, 241000, People’s Republic of China
                [5 ]Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College , Wuhu, 241000, People’s Republic of China
                Author notes
                Correspondence: Jian Zuo Department of Traditional Chinese Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) , Wuhu, 241000, People’s Republic of China Email zuojian8178@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-6800-4919
                Article
                320599
                10.2147/DDDT.S320599
                8291661
                34295151
                d4164780-870c-4ea5-82c6-cd5c27632d21
                © 2021 Wang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 17 May 2021
                : 09 July 2021
                Page count
                Figures: 6, References: 32, Pages: 14
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                fat metabolism,qing-luo-yin,rheumatoid arthritis,macrophages polarization,adipokine,(pre)-adipocytes

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