{"title":"Coadministration of Monophosphoryl Lipid and Curcumin Modulates Neuroprotective Effects in LPS Stimulated Rat Primary Microglial Cells.","authors":"Maryam Hooshmand, Ahmad Asoodeh","doi":"10.1155/omcl/9422312","DOIUrl":null,"url":null,"abstract":"<p><p>Lipopolysaccharide (LPS)-induced activation of microglia triggers the release of neuroinflammatory molecules, contributing to the progression of neurodegenerative diseases. Targeting these neuroinflammatory molecules could serve as a potential therapeutic strategy. Given the evidence supporting the immune-boosting properties of curcumin (Curc) and the protective effects of monophosphoryl lipid A (MPL) in the central nervous system (CNS) related to Alzheimer's disease (AD), this study aimed to assess the anti-inflammatory effects of these compounds on primary rat microglial cells, which are crucial in the response to neuroinflammation. This in vitro study investigated the effects of Curc, MPL, and their coadministration (Curc + MPL) on inflammatory cytokine levels in activated microglial cells. Primary microglial cells were isolated from 1-day-old rats and treated with various concentrations of Curc, MPL, and Curc + MPL prior to LPS stimulation. Cell viability was assessed using the MTT assay, followed by the Griess assay to evaluate nitric oxide (NO) production. The levels of inflammatory cytokines interleukin-1<i>β</i> (IL-1<i>β</i>), tumor necrosis factor-alpha (TNF-<i>α</i>), and interleukin-6 (IL-6), as well as the gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), were analyzed via real-time PCR. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the protein levels of IL-1<i>β</i>, TNF-<i>α</i>, and IL-6. Our findings demonstrate that Curc and MPL possess antineuroinflammatory properties in LPS-stimulated microglial cells. Notably, the coadministration of Curc and MPL (Curc + MPL) significantly inhibited the production of pro-inflammatory cytokines IL-1<i>β</i>, TNF-<i>α</i>, and IL-6. Furthermore, Curc + MPL suppressed the expression of iNOS and COX-2. These results strongly suggest that Curc + MPL is a promising neuroprotective agent for the treatment of neurodegenerative disorders by mitigating neuroinflammatory responses.</p>","PeriodicalId":19657,"journal":{"name":"Oxidative Medicine and Cellular Longevity","volume":"2024 ","pages":"9422312"},"PeriodicalIF":0.0000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620803/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oxidative Medicine and Cellular Longevity","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/omcl/9422312","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Lipopolysaccharide (LPS)-induced activation of microglia triggers the release of neuroinflammatory molecules, contributing to the progression of neurodegenerative diseases. Targeting these neuroinflammatory molecules could serve as a potential therapeutic strategy. Given the evidence supporting the immune-boosting properties of curcumin (Curc) and the protective effects of monophosphoryl lipid A (MPL) in the central nervous system (CNS) related to Alzheimer's disease (AD), this study aimed to assess the anti-inflammatory effects of these compounds on primary rat microglial cells, which are crucial in the response to neuroinflammation. This in vitro study investigated the effects of Curc, MPL, and their coadministration (Curc + MPL) on inflammatory cytokine levels in activated microglial cells. Primary microglial cells were isolated from 1-day-old rats and treated with various concentrations of Curc, MPL, and Curc + MPL prior to LPS stimulation. Cell viability was assessed using the MTT assay, followed by the Griess assay to evaluate nitric oxide (NO) production. The levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), as well as the gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), were analyzed via real-time PCR. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the protein levels of IL-1β, TNF-α, and IL-6. Our findings demonstrate that Curc and MPL possess antineuroinflammatory properties in LPS-stimulated microglial cells. Notably, the coadministration of Curc and MPL (Curc + MPL) significantly inhibited the production of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Furthermore, Curc + MPL suppressed the expression of iNOS and COX-2. These results strongly suggest that Curc + MPL is a promising neuroprotective agent for the treatment of neurodegenerative disorders by mitigating neuroinflammatory responses.
期刊介绍:
Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in today’s scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering “bench to bedside” research into clinical strategies.