Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). Both NF-κB activation and NLRP3 inflammasome activation are implicated in LN pathogenesis, suggesting they are potential targets for LN treatment. Icariin, which is isolated from Chinese medicine Horn...

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Veröffentlicht in:Life sciences (1973) 2018-09, Vol.208, p.26-32
Hauptverfasser: Su, Bofeng, Ye, Hong, You, Xiaohan, Ni, Haizhen, Chen, Xuduan, Li, Linlin
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creator Su, Bofeng
Ye, Hong
You, Xiaohan
Ni, Haizhen
Chen, Xuduan
Li, Linlin
description Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). Both NF-κB activation and NLRP3 inflammasome activation are implicated in LN pathogenesis, suggesting they are potential targets for LN treatment. Icariin, which is isolated from Chinese medicine Horny Goat Weed (Ying Yang Huo), has been shown to have anti-inflammation activity, and inhibit activations of both NF-κB and NLRP3 inflammasome. In present study, the effects of icariin on LN were evaluated in MRL/lpr mice. We treated MRL/lpr mice with icariin for 8 weeks and then analyzed the renal function and kidney pathology. We monitored the levels of anti-dsDNA antibody and the deposition of immune complex after icariin treatment. We also detected the macrophage infiltration, NF-κB activation, NLRP3 inflammasome activation and inflammatory cytokine TNF-α production in MRL/lpr mice after icariin treatment. We found that MRL/lpr mice treated with icariin displayed significantly attenuated the renal disease. Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1β production in MRL/lpr mice. Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.
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Both NF-κB activation and NLRP3 inflammasome activation are implicated in LN pathogenesis, suggesting they are potential targets for LN treatment. Icariin, which is isolated from Chinese medicine Horny Goat Weed (Ying Yang Huo), has been shown to have anti-inflammation activity, and inhibit activations of both NF-κB and NLRP3 inflammasome. In present study, the effects of icariin on LN were evaluated in MRL/lpr mice. We treated MRL/lpr mice with icariin for 8 weeks and then analyzed the renal function and kidney pathology. We monitored the levels of anti-dsDNA antibody and the deposition of immune complex after icariin treatment. We also detected the macrophage infiltration, NF-κB activation, NLRP3 inflammasome activation and inflammatory cytokine TNF-α production in MRL/lpr mice after icariin treatment. We found that MRL/lpr mice treated with icariin displayed significantly attenuated the renal disease. Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1β production in MRL/lpr mice. 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Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1β production in MRL/lpr mice. Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.</description><subject>Animals</subject><subject>Female</subject><subject>Flavonoids - pharmacology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Icariin</subject><subject>Inflammasome</subject><subject>Inflammasomes - antagonists &amp; inhibitors</subject><subject>Kidney Diseases - immunology</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - prevention &amp; control</subject><subject>Lupus nephritis</subject><subject>Lupus Nephritis - immunology</subject><subject>Lupus Nephritis - metabolism</subject><subject>Lupus Nephritis - pathology</subject><subject>Lupus Nephritis - prevention &amp; control</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred MRL lpr</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - physiology</subject><subject>Signal Transduction - drug effects</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1O3DAQx62qqCy0D9BL5WMvCeM4HxtxahFf0gpQxd3y2uPurBIn2MkiXq0PwTNhtNAjp9FofvPXzI-x7wJyAaI-2eadi3kBYplDkwO0n9hCLJs2g1qKz2wBUJSZLKA6ZEcxbgGgqhr5hR1KEGWdEhaMro0ORJ7rrsMd6Qkj7-dAHnk3j3PkHsdNoIkiT1NOfkPr1Pm__OYie_73m2sz0U5PNHg-6mnzqJ-49pbfrP7cyYS7Tve9jkOPX9mB013Eb2_1mN1fnN-fXWWr28vrs1-rzMhKTlll2xrT3aY00mqzdK1pnbNrKUS6vZbQwBIEFm1RCOcgcU5Li3bdNGAMymP2cx87huFhxjipnqLBrtMehzmqAtqyFFVdiYSKPWrCEGNAp8ZAvQ5PSoB6Fay2KglWr4IVNCoJTjs_3uLndY_2_8a70QSc7gFMP-4Ig4qG0Bu0FNBMyg70QfwLySCNaw</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Su, Bofeng</creator><creator>Ye, Hong</creator><creator>You, Xiaohan</creator><creator>Ni, Haizhen</creator><creator>Chen, Xuduan</creator><creator>Li, Linlin</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6272-7294</orcidid></search><sort><creationdate>20180901</creationdate><title>Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome</title><author>Su, Bofeng ; 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Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1β production in MRL/lpr mice. Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>30146016</pmid><doi>10.1016/j.lfs.2018.07.009</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-6272-7294</orcidid></addata></record>
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subjects Animals
Female
Flavonoids - pharmacology
Gene Expression Regulation - drug effects
Icariin
Inflammasome
Inflammasomes - antagonists & inhibitors
Kidney Diseases - immunology
Kidney Diseases - metabolism
Kidney Diseases - pathology
Kidney Diseases - prevention & control
Lupus nephritis
Lupus Nephritis - immunology
Lupus Nephritis - metabolism
Lupus Nephritis - pathology
Lupus Nephritis - prevention & control
Male
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
NF-kappa B - metabolism
NF-κB
NLR Family, Pyrin Domain-Containing 3 Protein - physiology
Signal Transduction - drug effects
title Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome
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