Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain

Reinicke, Madlen; Leyh, Judith; Zimmermann, S; Chey, Soroth; Brkovic, Ilijana Begcevic; Wassermann, Christin; Landmann, Julia; Lütjohann, Dieter; Isermann, Berend; Bechmann, Ingo; Ceglarek, Uta

doi:10.3390/ijms222413207

Cited by 5 publications

(3 citation statements)

References 52 publications

(71 reference statements)

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“…In addition, PS can reduce cholesterol and lipid-lowering, as well as resist atherosclerosis and immune regulation. PS crosses the blood-brain barrier, regulates lipid-derived pro-inflammatory mediators and plays an anti-neuroinflammation role [ 22 ]. It also has the ability to accumulate in the brain [ 23 ], which is of great significance for the regulation of neurodegenerative pathways.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Sun

et al. 2022

PLoS ONE

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Purpose To study the effects of Lu-tong Granules (LTG) in ICH etermine the underlying mechanism of molecular network Methods Modern bioinformatics and network pharmacology methods were used to predict molecular network mechanisms between ICH and LTG. Animal experiments were carried out to verify the effect of LTG for the treatment of ICH, combined with behavior test and morphologic detection. Results Forty-three active components in LTG and involved 192 gene targets were identified successfully. Moreoner, they were intersected with 1132 genes of ICH,88 intersection targets were obtained. subsequently, Cytoscape was used to screen Hub genes, in which,6 core molecules, including AKT1, IL6, VEGFA, CASP3, JUN and MMP9 were recognized. Furthermore, we constructed Six core compounds by " disease-drug-active ingredient-target-KEGG " (D-D-A-T-K) network, showed including quercetin, luteolin, β sitosterol, stigmasterol, kaempferol and formononetin, and PPI protein network interaction showed that AKT1:OS3 and CNA2:DKN1A had the highest correlation. Whereas the enrichment of GO and KEGG indicated that LTG was most likely to play a therapeutic role in ICH through AGE-RAGE signaling pathway in diabetic complications. Integrated analysis also showed that the first 10 pathways of KEGG are integrated into 59 genes, among which 6 core genes are closely involved. Lastly, molecular docking showed that there was a good binding activity between the core components and the core genes, and animal experiments confirmed effect of LTG in the treatment of ICH, by using TTC staining and behavior test. Conclusion LTG are effective for the treatment of ICH, the underlying mechanism could be involved in gene network including anti-inflammatory response, nerve repair, analgesia, anti-epilepsy and other aspects.

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Section: Discussionmentioning

confidence: 99%

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Sun

et al. 2022

PLoS ONE

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“…Recent research has demonstrated that dietary phytosterols can pass the blood–brain barrier, accumulate in the brain and nervous system, and possibly exert antineuroinflammatory effects (Reinicke et al, 2021). Stigmasterol (C 29 H 48 O, stigmasta‐5,22‐dien‐3‐ol) is a phytosterol that has antiinflammatory and neuroprotective properties (Jie, Yang, Yang, et al, 2022; Mo et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Si,

Li,

Jing

et al. 2023

Phytotherapy Research

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Abstract(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme‐linked immunosorbent assay, hematoxylin‐esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT‐PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL‐1β and IL‐8 levels and increased serum IL‐4 and TGF‐β levels in CCI rats. Stigmasterol reduced IL‐1β, COX‐2, and TLR4 expression in the right sciatic nerve and IL‐1β expression in the spinal cord. Stigmasterol reduced the expression of Iba‐1, TLR4, MyD88, pNF‐κB, pP38 MAPK, pJNK, pERK, COX‐2, IL‐1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL‐10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)‐induced microglia and decreased the expression of Iba‐1, TLR4, MyD88, pNF‐κB, pP38 MAPK, pJNK, pERK, iNOS, COX‐2, and IL‐1β in LPS‐treated microglia while increasing the expression of Arg‐1 and IL‐10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate NP.

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“…Animal investigations showed that PSs accumulate in the brain [ 11 , 12 ]. Recently, PSs were also identified in human cortex samples [ 13 ]. Incorporated into cell membranes, PSs may affect membrane fluidity, cell signaling and the sensitivity of cells to oxidative stress [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Non-Cholesterol Sterols in Microglia Cell Membranes Using Targeted Mass Spectrometry

Brkovic

Reinicke

Chey

et al. 2023

Cells

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Background: Non-cholesterol sterols, as well as plant sterols, cross the blood–brain barrier and, thus, can be incorporated into cell membranes, affecting the cell’s inflammatory response. The aim of our work was to develop an analytical protocol for a quantitative assessment of the sterol composition within the membrane microdomains of microglia. Methods: A protocol for cell membrane isolation using OptiPrepTM gradient ultracentrifugation, in combination with a targeted mass spectrometry (LC-MS/MS)-based assay, was developed and validated for the quantitative analysis of free sterols in microglia cell membranes. Results: Utilizing an established LC-MS/MS assay, cholesterol and seven non-cholesterol sterols were analyzed with a limit of detection from 0.001 to 0.05 mg/L. Applying the detergent-free isolation of SIM-A9 microglia cell membranes, cholesterol (CH), desmosterol (DE), lanosterol (LA) stigmasterol (ST), beta-sitosterol (SI) and campesterol (CA) were quantified with coefficients of variations between 6 and 29% (fractions 4–6, n = 5). The highest concentrations of non-CH sterols within the microglia plasma membranes were found in the microdomain region (DE>LA>SI>ST>CA), with ratios to CH ranging from 2.3 to 435 lower abundancies. Conclusion: By applying our newly developed and validated analytical protocol, we show that the non-CH sterol concentration is about 38% of the total sterol content in microglia membrane microdomains. Further investigations must clarify how changes in the non-sterol composition influence membrane fluidity and cell signaling.

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Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain

Cited by 5 publications

References 52 publications

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Mechanism of gene network in the treatment of intracerebral hemorrhage by natural plant drugs in Lutong granules

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Characterization of Non-Cholesterol Sterols in Microglia Cell Membranes Using Targeted Mass Spectrometry

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