Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis

Li, Yi Rong; Chen, Der Yuan; Chu, Ching-Liang; Li, Shiming; Chen, Yu-Kuo; Wu, Chao‐Liang; Lin, Chi Chen

doi:10.1016/j.jnutbio.2015.07.016

Cited by 62 publications

(41 citation statements)

References 58 publications

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“…Wogonoside inhibits LPS-induced angiogenesis both in vitro and in vivo [45]. Naringenin can manipulate the immunostimulatory properties of DCs and thus represents a potential therapeutic for the treatment of RA [46]. In addition, Formononetin can increase allergic responses by enhancing IL-4 production in T cells [47].…”

Section: Discussionmentioning

confidence: 99%

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

Li¹,

Wei²,

Li³

et al. 2017

BMC Complement Altern Med

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BackgroundXian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment.MethodsA high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MSn) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis.ResultsIn our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3+ T cells and CD3−CD19+ B cells significantly. However, XFHM had no significant effect on CD3−NK1.1+ NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling.ConclusionsXFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA in modern complementary and alternative therapeutics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1526-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

Li¹,

Wei²,

Li³

et al. 2017

BMC Complement Altern Med

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“…The other is the MyD88-independent pathway, which induces IRF3 activation and the production of IFNs, as well as IFN inducible mediators such as RANTES and IP-102021. Previously, naringenin was reported to inhibit the activation of MAPK and NF-κB signalling pathways in epithelia cells and dendritic cells, which was required to suppress inflammation or cell maturation2223. However, it is not known whether naringenin affects the MyD88-independent pathway.…”

Section: Discussionmentioning

confidence: 99%

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

Liu

Wang

Fan

et al. 2016

Sci Rep

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Excessive activation of the TLR4 signalling pathway is critical for inflammation-associated disorders, while negative regulators play key roles in restraining TLR4 from over-activation. Naringenin is a citrus flavonoid with remarkable anti-inflammatory activity, but the mechanisms underlying its inhibition of LPS/TLR4 signalling are less clear. This study investigated the molecular targets and therapeutic effects of naringenin in vitro and in vivo. In LPS-stimulated murine macrophages, naringenin suppressed the expression of TNF-α, IL-6, TLR4, inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2) and NADPH oxidase-2 (NOX2). Naringenin also inhibited NF-κB and mitogen-activated protein kinase (MAPK) activation. However, it did not affect the IRF3 signalling pathway or interferon production, which upregulate activating transcription factor 3 (ATF3), an inducible negative regulator of TLR4 signalling. Naringenin was demonstrated to directly increase ATF3 expression. Inhibition of AMPK and its upstream calcium-dependent signalling reduced ATF3 expression and dampened the anti-inflammatory activity of naringenin. In murine endotoxaemia models, naringenin ameliorated pro-inflammatory reactions and improved survival. Furthermore, it induced AMPK activation in lung tissues, which was required for ATF3 upregulation and the enhanced anti-inflammatory activity. Overall, this study reveals a novel mechanism of naringenin through AMPK-ATF3-dependent negative regulation of the LPS/TLR4 signalling pathway, which thereby confers protection against murine endotoxaemia.

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“…Synovial DC was found activated in vivo with upregulation of MHC and costimulatory molecules (CD80, CD86) . In fact, studies suggest that suppression of DC maturation and activation attenuates RA . Dendritic cell activation can be assessed by monitoring the expression of cell surface activation markers CD80, CD86 and MHC class II .…”

Section: Discussionmentioning

confidence: 72%

“…Immature DCs and spleen cells were stained with conjugated antibodies specific for mouse CD11c‐eFluor450, MHCII‐Alexa Fluor 488, CD86‐APC, CD80‐PE, CD4‐FITC and IL17‐PerCP‐Cy™5.5 in PBS + 0.1%BSA at 4 °C for 15 min. After staining, 5 × 10 4 cells were acquired on BD FACSAria™ and analysed by FACS Diva software on a FACS Aria …”

Section: Methodsmentioning

confidence: 99%

“…After staining, 5 9 10 4 cells were acquired on BD FACSAria TM and analysed by FACS Diva software on a FACS Aria. [19] Lymphocyte proliferation On day of sacrifice, spleens were collected and flushed by RPMI with the help of syringe and then gently minced, passed through 70-lm cell strainer. RBC was lysed with ACK RBC lysis buffer.…”

Section: Histopathological Analysismentioning

confidence: 99%

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Standardized Xylocarpus moluccensis fruit fraction mitigates collagen-induced arthritis in mice by regulating immune response

Gupta

Kumar

Pal

et al. 2020

Journal of Pharmacy and Pharmacology

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Objective This study was undertaken to evaluate the effect of Xylocarpus moluccensis fruit fraction (F018) on the pathogenesis of collagen‐induced arthritis in mice. Methods Arthritis was induced by intradermal injection of collagen (2 mg/ml) with complete Freund’s adjuvant in DBA/1J mice. F018 was administered orally at 1, 3 and 10 mg/kg for 20 days. Disease progression and mechanism were assessed by micro‐CT analysis, RT‐PCR, flow cytometry assay, myeloperoxidase (MPO) and MTT assay. Results F018 at 3 and 10 mg/kg significantly reduced paw thickness, clinical score, mononuclear cell infiltration and collagen layer depletion in the knee section of collagen‐induced arthritis (CIA) mice when compared with collagen‐induced arthritis mice alone. Furthermore, F018 treatment in collagen‐induced arthritis mice significantly recovered bone volume and trabecular number and decreased the trabecular space by modulating RANKL and OPG mRNA expression in the synovial tissue. F018 treatment in collagen‐induced arthritis mice significantly attenuated spleen index, lymphocyte proliferation and paw myeloperoxidase (MPO) activity, pro‐inflammatory cytokine TNFα, IL1β, and IL6 mRNA expression and enhanced IL10 mRNA expression in paw tissue. Furthermore, F018 treatment in collagen‐induced arthritis mice significantly reduced splenic dendritic cell maturation and Th17 cells. In culture, F018 significantly decreased collagen‐induced arthritis‐FLS proliferation and promoted apoptosis. Conclusion F018 may serve as a potential curative agent for arthritis.

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Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis

Cited by 62 publications

References 58 publications

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

The citrus flavonoid naringenin confers protection in a murine endotoxaemia model through AMPK-ATF3-dependent negative regulation of the TLR4 signalling pathway

Standardized Xylocarpus moluccensis fruit fraction mitigates collagen-induced arthritis in mice by regulating immune response

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