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      Drug Design, Development and Therapy (submit here)

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      Effect of Eriodictyol on Collagen-Induced Arthritis in Rats by Akt/HIF-1α Pathway

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          Abstract

          Purpose

          The aim of the experiment was to explore the effect of eriodictyol (ERI) on arthritis.

          Methods

          We established a rat model of collagen-induced rheumatoid arthritis (CIA) using type II collagen plus Freund’s complete adjuvant. We evaluated the degree of paw swelling, joint pathology, inflammatory cytokine levels, and the Akt/hypoxia-inducible factor (HIF)-1α signaling pathway in the CIA rats.

          Results

          ERI significantly ameliorated joint swelling; improved joint pathology; and suppressed the release of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha. Moreover, ERI inhibited the Akt/HIF-1α pathway in the joints of rats and in lipopolysaccharide-treated RAW264.7 cells.

          Conclusion

          ERI ameliorated arthritis in a manner involving the Akt/HIF-1α signaling pathway.

          Most cited references22

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          Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats.

          Claudio Bucolo, Gian Marco Leggio, Filippo Drago … (2012)
          Diabetic retinopathy is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. We hypothesized that eriodictyol, one of the most abundant dietary flavonoids, could be effective against diabetic retinopathy, which involves significant oxidative stress and inflammation. The aim of the present study was to investigate the effects of eriodictyol in early retinal and plasma changes of streptozotocin-induced diabetic rats. The effect of eriodictyol treatment (0.1, 1, 10 mg/kg daily for 10 days) was evaluated by TNF-α, ICAM-1, VEGF, and eNOS protein levels measurement in the retina, plasma lipid peroxidation, and blood-retinal barrier (BRB) integrity. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina from diabetic rats. Eriodictyol treatment significantly lowered retinal TNF-α, ICAM-1, VEGF, and eNOS in a dose-dependent manner. Further, treatment with eriodictyol significantly suppressed diabetes-related lipid peroxidation, as well as the BRB breakdown. These data demonstrated that eriodictyol attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the BRB in early diabetic rats. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis.

            Gemma S Morgan, Paul P. Tak, K A Zwinderman … (2004)
            To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA). Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model. After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 +/- 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy. Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.
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              Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis.

              Aroldo Rizzo, Antonio Manzo, Giuliana Guggino … (2015)
              IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): DDDT
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 29 April 2020
                Publication date Collection: 2020
                Volume: 14
                Pages: 1633-1639
                Affiliations
                [1 ]Department of Orthopedics, Zhujiang Hospital, Southern Medical University , Guangzhou 510282, People’s Republic of China
                [2 ]Department of Orthopedics, The Sixth Peoples Hospital of Huizhou , Huizhou 516211, People’s Republic of China
                [3 ]Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, People’s Republic of China
                Author notes
                Correspondence: Bo Yu Email yubozj@yeah.net
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-9973-2011
                Article
                Publisher ID: 239662
                DOI: 10.2147/DDDT.S239662
                PMC ID: 7196781
                SO-VID: 8138d255-7e8f-4c9c-a20b-bb15cdbfffa3
                Copyright © © 2020 Lei et al.
                License:

                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
                Date received : 22 November 2019
                Date accepted : 25 February 2020
                Page count
                Figures: 5, References: 27, Pages: 7
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: eriodictyol,arthritis,inflammation,akt/hif-1α pathway
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: eriodictyol, arthritis, inflammation, akt/hif-1α pathway

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