Microglial activation in Alzheimer's disease: The role of flavonoids and microRNAs

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(1), P. 47 - 77

Published: March 16, 2022

Abstract Alzheimer's disease (AD) is the most common form of senile dementia and characterized by progressive cognitive impairment neuronal degeneration. Microglial activation an important pathologic hallmark AD. During progression, microglial cells switch from alternative or anti-inflammatory neuroprotective profile (M2) to a classic proinflammatory neurotoxic (M1). Phenotypically, M1 microglia inflammatory signaling pathways that cause increased expression genes, including those coding for cytokines chemokines. This microglia-mediated neuroinflammation contributes cell death. Recent studies in have shown group plant-derived compounds, known as flavonoids, possess properties therefore exert effect through regulating activation. Here, we discuss how flavonoids can promote phenotype M2 this represents valuable opportunity development novel therapeutic strategies blunt boost recovery We also review certain inhibit their action on microglia-specific microRNAs (miRNAs), which constitute key approach different neuropathologies involving component, Finally, propose targets miRNAs may be considered AD treatment.

Language: Английский

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Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV‐induced skin aging by activating Nrf2 defense mechanisms

Phytotherapy Research, Journal Year: 2022, Volume and Issue: 36(8), P. 3276 - 3294

Published: July 12, 2022

Abstract Oxidative stress damage can lead to premature skin aging or age‐related disorders. Therefore, strategies improve oxidative stress‐induced are needed protect the and treat diseases. This study aimed determine whether flavonoid corylin derived from Psoralea corylifolia prevent UV‐induced if so, explore potential molecular mechanisms. We found that potently blocked photoaging in mice by reducing increasing nuclear expression of factor‐erythroid factor 2‐related 2 Nrf2. also stimulated Nrf2 translocation into nucleus increased delivery its target antioxidant genes together with Kelch‐like ECH‐associated protein 1 (Keap1) dissociate These findings indicate could inhibiting via Keap1‐Nrf2 mouse cells. Thus, activation might be a therapeutic for preventing diseases caused aging. Our provided evidence warrants further investigation plant ingredients facilitate discovery novel therapies targeting

Language: Английский

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Pin1 Promotes NLRP3 Inflammasome Activation by Phosphorylation of p38 MAPK Pathway in Septic Shock

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 25, 2021

Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that can specifically recognize and isomerize phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif, change conformation of proteins through protein phosphorylation, thus regulate various cellular processes in body. plays an important role cancer, Alzheimer’s disease, autoimmune diseases. However, specific mechanism regulation LPS-induced septic shock unclear. Here, we found lack reduced mortality organ damage mice, NLRP3 inflammasome activation also was this process. We further confirmed affect expression NLRP3, ASC, Caspase1, process be regulated p38 MAPK pathway. analyzed signaling pathway highly expressed showed a positive correlation with Gene Expression Omnibus database. could phosphorylation MAPK, have no obvious difference extracellular signal-regulated kinases (ERK) Jun-amino-terminal kinase (JNK) signaling. p-p38 interacted, but not directly. In addition, deficiency inhibited cleavage gasdermin D (GSDMD) promoted death macrophages LPS treatment, secretion inflammatory cytokines including IL-1β IL-18. general, our results suggest regulates by macrophages. Thus, may potential target for treatment diseases such as shock.

Language: Английский

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Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(10), P. 1046 - 1046

Published: Oct. 14, 2021

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have anti-inflammatory activities. Herein, we investigated therapeutic potential corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro vivo. The levels proinflammatory cytokine secretions were analyzed by ELISA; expressions inflammation-associated proteins detected using Western blot; number immune cell infiltrations bronchial alveolar lavage fluid (BALF) multicolor flow cytometry tissues hematoxylin eosin (HE) staining, respectively. Experimental results indicated that attenuated LPS-induced IL-6 production human epithelial cells (HBEC3-KT cells). In intratracheal ALI mice, tissue damage, suppressed inflammatory infiltration, decreased TNF-α BALF serum. Moreover, it further inhibited phosphorylation mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, repressed activation signal transducer activator transcription 3 (STAT3) lungs. Collectively, our are first demonstrate effects suggest significant as novel agent for ALI.

Language: Английский

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TLR4-IN-C34 Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses via Downregulating TLR4/MyD88/NF-κB/NLRP3 Signaling Pathway and Reducing ROS Generation in BV2 Cells

Inflammation, Journal Year: 2021, Volume and Issue: 45(2), P. 838 - 850

Published: Nov. 2, 2021

Language: Английский

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