Abstract Aims 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. Main methods 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. Key findings 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. Significance Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.
Disease heterogeneity remains a major challenge for the understanding of systemic lupus erythematosus (SLE). Recent work has revealed the important role of nonimmune factors in the development of end-organ damage involvement, shifting the current paradigm that views SLE as a disease inflicted by a disturbed immune system on passive target organs. Here, we discuss the pathogenesis of lupus nephritis in a comprehensive manner, by incorporating the role that target organs play by withstanding and m...
Previous findings have identified that tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is associated with lupus nephritis (LN) activity status; however, the mechanism involved remains unclear. The present study aimed to investigate the roles of TWEAK and the nuclear factor (NF)-κB signaling pathway in LN. TWEAK levels in the blood and urine of patients with LN or non-LN systemic lupus erythematosus were measured by ELISA and compared with those in healthy controls. TWEAK expressi...
#1Jian Fang(Southern Medical University)H-Index: 1
#2Yongjun Zhang(Southern Medical University)H-Index: 1
Icariin is a major bioactive pharmaceutical constituent isolated from Chinese medicine Horny Goat Weed with potent cardiovascular protective functions. Emerging evidence in the past decade has shown that Icariin possesses multiple atheroprotective functions, through multiple mechanisms, including attenuating DNA damage, correcting endothelial dysfunction, inhibiting the proliferation and migration of smooth muscle cells, repressing macrophage-derived foam cell formation and inflammatory response...
#1Lei Zhang(HMU: Harbin Medical University)H-Index: 8
#1Lei Zhang(HMU: Harbin Medical University)H-Index: 10
Last. Li-Rong Hao(HMU: Harbin Medical University)H-Index: 1
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Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti-inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague–Dawley rats by oral and intravenous immunization with bovine gamm...
Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1β (IL-1β) and IL-18...
Abstract Icariin (ICA), a flavonoid extracted from the traditional Chinese herb Herba Epimedii that can freely cross the blood–brain barrier, inhibits neuroinflammation and attenuates oxidative stress damage. Our previous studies demonstrated that icariin exerts an antidepressant-like activity in a social defeat mouse model. However, it is unknown whether icariin is beneficial for the treatment of depression via its modulation of oxidative stress and neuroinflammation. The objective of this stud...
The role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn the cytokines IL-1β and IL-18, is important in lupus pathogenesis. This review will summarize the recent discoveries exploring the role of the inflammasome machinery in SLE. Immune complexes can activate the NLRP3 inflammasome, and S...
#1Jijun Zhao(SYSU: Sun Yat-sen University)H-Index: 14
#2Hongyue Wang(SYSU: Sun Yat-sen University)H-Index: 10
Last. Shu Man Fu(UVA: University of Virginia)H-Index: 38
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The most commonly affected organ in systemic lupus erythematosus (SLE) is the kidney, and lupus nephritis (LN) is a very frequent and potentially fatal complication of SLE (1). Despite the fact that the prognosis has improved over the past few decades, lupus still progresses to end-stage renal disease within 10 years of diagnosis in 10–15% of patients (2). Thus, development of novel therapeutic strategies remains a priority, and to achieve this aim, identification of the specific pathways involv...
#1Jijun Zhao(SYSU: Sun Yat-sen University)H-Index: 14
#2Hui Zhang(SYSU: Sun Yat-sen University)H-Index: 8
Last. Niansheng Yang(SYSU: Sun Yat-sen University)H-Index: 16
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Abstract Nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome are involved in inflammation and autoimmunity. In vitro data have shown that Bay11-7082 selectively inhibits NLRP3 inflammasome activity independent of NF-κB activity. In this study, we evaluated the therapeutic effects of Bay11-7082 on murine lupus nephritis (LN) in vivo. Twelve-week-old MRL/ lpr mice were treated with either Bay11-7082 (5 mg/kg) or vehicle (DMSO/PBS buffer) by intraperitoneal injection thrice per week for 8 weeks. ...
Neutrophil extracellular traps (NETs) represent an important defense mechanism against microorganisms. Clearance of NETs is impaired in a subset of patients with systemic lupus erythematosus, and NETosis is increased in neutrophils and, particularly, in low-density granulocytes derived from lupus patients. NETs are toxic to the endothelium, expose immunostimulatory molecules, activate plasmacytoid dendritic cells, and may participate in organ damage through incompletely characterized pathways. T...
Abstract Objective Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural. Methods Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chroma...
#1Li Chen(CAS: Chinese Academy of Sciences)H-Index: 2
#2Shi-Qi Cao(CAS: Chinese Academy of Sciences)H-Index: 1
Last. Jian-Ping Zuo(CAS: Chinese Academy of Sciences)H-Index: 32
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Autoimmune diseases are chronic immune diseases characterized by dysregulation of immune system, which ultimately results in a disruption in self-antigen tolerance. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) play essential roles in various autoimmune diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, multiple sclerosis (MS), etc. NLR proteins, consisting of a C-term...
Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to pos...
Rheumatoid arthritis (RA) is considered to be a chronic autoimmune disease, pathogenesis of RA is complex and effective treatments for RA is still lacking. Previous studies found that microRNAs (mi...
Abstract NOD-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular receptor that senses foreign pathogens and endogenous danger signals. It assembles with apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 to form a multimeric protein called the NLRP3 inflammasome. Among its various functions, the NLRP3 inflammasome can induce the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 while also promoting gasdermin D (GSDMD)-mediat...
#1Linjiang Song(CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 1
#2Xian Chen(CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 1
Last. Xin Liang(CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 1
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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...
#1Shin-Ruen Yang(NDMC: National Defense Medical Center)H-Index: 2
#2Kuo-Feng Hua(NIU: National Ilan University)H-Index: 27
Last. Ann Chen(NDMC: National Defense Medical Center)H-Index: 34
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Abstract Xenon, an inert anesthetic gas, is increasingly recognized to possess desirable properties including cytoprotective and anti-inflammatory effects. Here we evaluated the effects of xenon on the progression of lupus nephritis (LN) in a mouse model. A two hour exposure of either 70% xenon or 70% nitrogen balanced with oxygen was administered daily for five weeks to female NZB/W F1 mice that had been induced to develop accelerated and severe LN. Xenon treatment improved kidney function and ...
Abstract Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-...