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

Su, Bofeng; Ye, Hong; You, Xin; Ni, Hong-Bo; Chen, Xuduan; Li, Linlin

doi:10.1016/j.lfs.2018.07.009

Cited by 63 publications

(43 citation statements)

References 29 publications

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“…It has been established that NLRP3 inflammasome and its associated signals, 45 together with active form NF-kB, play a critical role in regulating priming signals of the inflammasome. 15,16 In the present study, we found that Xe treatment significantly reduced renal phosphorylated-NF-kB p65 (Figure 4f and g) and renal NF-kB p65 activity (Figure 4e), and increased HIF-1a, a protective barrier against NF-kB activation, 30,49 in the ASLN mice (Figure 4f and g). Interestingly, Xe treatment also inhibited splenic B-cell activation and reduced the serum level of the anti-double-stranded DNA antibody and glomerular deposition of IgG and C3.…”

Section: Discussionsupporting

confidence: 61%

“…Nuclear factor (NF)-kB and NLRP3 inflammasome are implicated in the pathogenesis of glomerular injury in LN. [13][14][15] NF-kB-dependent upregulation of intercellular adhesion molecule (ICAM)-1 is involved in the pathogenesis of systemic lupus erythematosus 16 and LN, 17,18 and NF-kB activation is considered a major disease-developing mediator of LN. 19,20 Of note, immune complexes obtained from systemic lupus erythematosus patients can trigger NLRP3 inflammasome activation, thus contributing to the development of renal lesions.…”

Section: Translational Statementmentioning

confidence: 99%

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Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

Yang

Hua

Chu

et al. 2020

Kidney International

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Section: Discussionsupporting

confidence: 61%

Section: Translational Statementmentioning

confidence: 99%

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

Yang

Hua

Chu

et al. 2020

Kidney International

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“…Subsequently, the NF‐κB transcriptional complex is released into the nucleus where it binds negative regulatory DNA elements and promotes the transcription of pro ‐ metastatic genes 35,36 . Previous studies have shown that icariin can alleviate murine lupus nephritis and improve anemia hematopoietic stem cell function by inhibiting the activation of NF‐κB 24,25 . In this study, we found that the expression levels of p‐IκBα in the cytoplasm and NF‐κB p65 in the nucleus in 4T1 cells were both significantly inhibited following treatment with icariin.…”

Section: Discussionmentioning

confidence: 56%

“…Icariin, a prenylated flavonol glycoside, which is extracted from the medical plant Herba Epimedii (Figure 1A), has demonstrated numerous pharmacological actions, including as an aphrodisiac, osteogenic, antidepressant, cardiovascular protective, and has immunomodulatory activities 21‐23 . It has been reported that icariin can serve as an effective NF‐κB inhibitor to alleviated murine lupus nephritis and improved Fanconi anemia hematopoietic stem cell function 24,25 . In recent years, studies have demonstrated the anti‐cancer effect of icariin against osteosarcoma, prostate, lung, and gastric cancer cells 26‐28 .…”

Section: Introductionmentioning

confidence: 99%

Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer

et al. 2020

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Abnormal activation of the nuclear factor‐kappa B (NF‐κB) signaling pathway is closely implicated in triple‐negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti‐cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration‐ and time‐dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria‐mediated pathway, as indicated by the upregulated ratio of Bax/Bcl‐2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF‐κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss‐128167, an inhibitor of SIRT6, dramatically attenuated anti‐migration and anti‐invasion effects of icariin. Transcriptomic analysis verified that impairment of NF‐κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti‐pulmonary metastasis effect in a tumor mouse model of MDA‐MB‐231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF‐κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

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“…Cytokines can be produced when the NF-κB signaling pathway is activated during the progression of a direct autoantibody-mediated tissue injury and the deposition of complement-fixing immune complexes, inducing chronic inflammatory response. Importantly, the activation of NF-κB is critically responsible for the secretion of cytokines including, IL-6, IL-1β, PTGS2, CCL2, and TNF-α [50,51]. IL-1β and IL-6 belong to the IL family as inflammatory cytokines and could impact on SLEDAI as inflammatory mediators in the active stage of disease.…”

Section: Discussionmentioning

confidence: 99%

Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology

Yang

Xie

Zhong

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Systemic lupus erythematosus (SLE) is a refractory autoimmune disease. Zhibai Dihuang Wan (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients’ morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we collected putative targets of ZDW based on TCMSP, GeneCards, and STITCH databases and built a network containing the interactions between the putative targets of ZDW and known therapeutic targets of SLE. Then, the key hubs were imported to DAVID Bioinformatics Resources 6.7 to perform gene ontology biological process (GOBP) and pathway enrichment analysis. A total of 95 nodes including 73 putative targets of ZDW were determined as major hubs in terms of their node degree. The results of GOBP and pathway enrichment analysis indicated that putative targets of ZDW mostly were involved in various pathways associated with inflammatory response and apoptosis. More importantly, eleven putative targets of ZDW (CASP3, BCL2, BAX, CYCS, NFKB1, NFKBIA, IL-6, IL-1β, PTGS2, CCL2, and TNF-α) were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZDW acting on SLE. This study provides novel insights into the mechanisms of ZDW in SLE, from the molecular level to the pathway level.

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

Cited by 63 publications

References 29 publications

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

Xenon blunts NF-κB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice

Icariin‐induced inhibition of SIRT6/NF‐κB triggers redox mediated apoptosis and enhances anti‐tumor immunity in triple‐negative breast cancer

Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology

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