Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-κB and MAPK pathways

Zeng, Ke‐Wu; Li, Jun; Dong, Xin; Wang, Yinghong; Ma, Zhigui; Jiang, Yong; Jin, Hongwei; Tu, Pengfei

doi:10.1016/j.taap.2013.08.028

Cited by 41 publications

(31 citation statements)

References 39 publications

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“…Lee et al demonstrated that HG increases NF-κB transcription activity through the increased phosphorylation of IκBα [43]. In previous studies, other chalcone derivatives have demonstrated to inhibit NF-κB activation in LPS-, H2O2- [44] and even HGstimulated cell lines [25], as well as in several animal models [45]. Our results shown in Fig.…”

Section: Discussionsupporting

confidence: 64%

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

Fang

Wang

et al. 2015

Toxicology and Applied Pharmacology

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Section: Discussionsupporting

confidence: 64%

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

Fang

Wang

et al. 2015

Toxicology and Applied Pharmacology

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“…These data suggest that the induction of IFN-γ by GD-1 is mediated by PKD1-mediated NF-κB signaling pathway. Both PKC and ERK/MEK pathways could activate NF-κB transcriptional activities by phosphorylating IKKs via separate pathways [40] , [41] . Because the treatment of ERK/MEK inhibitors could not inhibit the effect of GD-1 on IFN-γ production (data not shown), NF-κB activation by GD-1 treatment could be mediated through the IKK phosphorylation by PKD1 via MAPK-independent pathway.…”

Section: Resultsmentioning

confidence: 99%

Genkwadaphnin Induces IFN-γ via PKD1/NF-κB/STAT1 Dependent Pathway in NK-92 Cells

Kang

Ahn

et al. 2014

PLoS ONE

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The flower buds of Daphne genkwa Sieb. et Zucc. have been used as a traditional Chinese medicine although their functional mechanisms have not been discovered yet. We have studied the potential effects of the plant extracts on natural killer (NK) cell activation, and isolated an active fraction. Genkwadaphnin (GD-1) displayed a potent efficacy to induce IFN-γ transcription in NK cells with concentration- and time-dependent manners. GD-1 treatment triggered the phosphorylation of PKD1, a member of PKC family, MEK and ERK, resulting in IKK activation to induce IκB degradation, and the nuclear localization of p65, an NF-κB subunit, which regulates IFN-γ transcription. GD-1 effect on IFN-γ production was blocked by the addition of Rottlerin, a PKC inhibitor, CID 755673, a PKD inhibitor, or Bay11-7082, an IKKα inhibitor. The nuclear localization of p65 was also inhibited by the kinase inhibitors. Secreted IFN-γ activates STAT1 phosphorylation as autocrine-loops to sustain its secretion. GD-1 induced the phosphorylation of STAT1 probably through the increase of IFN-γ. STAT1 inhibitor also abrogated the sustained IFN-γ secretion. These results suggest that GD-1 is involved in the activation of PKD1 and/or ERK pathway, which activate NK-κB triggering IFN-γ production. As positive feedback loops, secreted IFN-γ activates STAT1 and elongates its production in NK-92 cells.

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“…The small‐molecule FMHM, a natural derived AR inhibitor, was initially reported to suppress the expression of various inflammatory genes in microglia both in vitro and in vivo. Mechanistically FMHM suppresses the activity of AR‐dependent phospholipase C/protein kinase C signaling, resulting in downstream inactivation of NF‐κB inflammatory pathway (Zeng et al, ); (Figure ). More recently, two other AR inhibitors have been identified, Sorbinil and Zopolrestat, which significantly inhibit inflammatory cytokine expression by blocking NF‐κB and MAPK signaling pathways in Aβ‐treated microglia (X. M. Song et al, ); (Figure ).…”

Section: Metabolic Drugs and Molecular Pathways Which May Be Exploitementioning

confidence: 99%

How to reprogram microglia toward beneficial functions

Fumagalli

Lombardi

Gressèns

et al. 2018

Glia

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Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro-regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.

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Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via phospholipase C/protein kinase C-dependent NF-κB and MAPK pathways

Cited by 41 publications

References 39 publications

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

Genkwadaphnin Induces IFN-γ via PKD1/NF-κB/STAT1 Dependent Pathway in NK-92 Cells

How to reprogram microglia toward beneficial functions

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