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Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro
Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca(2+) homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603949/ https://www.ncbi.nlm.nih.gov/pubmed/36293507 http://dx.doi.org/10.3390/ijms232012651 |
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author | Fisher, Derek R. Zheng, Tong Bielinski, Donna F. Kelly, Megan E. Cahoon, Danielle S. Shukitt-Hale, Barbara |
author_facet | Fisher, Derek R. Zheng, Tong Bielinski, Donna F. Kelly, Megan E. Cahoon, Danielle S. Shukitt-Hale, Barbara |
author_sort | Fisher, Derek R. |
collection | PubMed |
description | Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca(2+) homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals exhibit potent anti-inflammatory activities which may mitigate these age-related CNS decrements. This study investigated the individual and combination effects of green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane on inflammation and dysregulation in Ca(2+) homeostasis to determine if the individual compounds were working synergistically and/or through independent mechanisms. Rat hippocampal neurons or highly aggressive proliferating immortalized (HAPI) microglial cells were pre-treated for a week with either the individual components or all in combination before inducing Ca(2+) buffering deficits with dopamine (DA, 0.1 µM for 2 h) or inflammation using lipopolysaccharide (LPS, 100 ng/mL for 18 h), respectively. The EGCG (3 µM) and combination protected against DA-induced deficits in Ca(2+) buffering (both % of cells that recovered and recovery time, p < 0.05). Additionally, the EGCG and combination reduced stress-mediated inflammation in HAPI rat microglial cells by attenuating LPS-induced nitrite release, inducible nitrous oxide synthase (iNOS) expression, and tumor necrosis factor-alpha (TNF-α) release (p < 0.05), but not cyclooxygenase-2 (COX-2) expression. Overall, broccoli sprouts (2 µM) and curcumin (1 µM) were not as effective as the EGCG or combination. Further research is needed to determine if dietary intervention with a variety of foods containing compounds such as those found in green tea, turmeric, or broccoli sprouts can play a role in reducing age-related CNS inflammation, microglial activation, and downstream signaling pathways that can lead to neuronal dysfunction. |
format | Online Article Text |
id | pubmed-9603949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96039492022-10-27 Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro Fisher, Derek R. Zheng, Tong Bielinski, Donna F. Kelly, Megan E. Cahoon, Danielle S. Shukitt-Hale, Barbara Int J Mol Sci Article Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca(2+) homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals exhibit potent anti-inflammatory activities which may mitigate these age-related CNS decrements. This study investigated the individual and combination effects of green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane on inflammation and dysregulation in Ca(2+) homeostasis to determine if the individual compounds were working synergistically and/or through independent mechanisms. Rat hippocampal neurons or highly aggressive proliferating immortalized (HAPI) microglial cells were pre-treated for a week with either the individual components or all in combination before inducing Ca(2+) buffering deficits with dopamine (DA, 0.1 µM for 2 h) or inflammation using lipopolysaccharide (LPS, 100 ng/mL for 18 h), respectively. The EGCG (3 µM) and combination protected against DA-induced deficits in Ca(2+) buffering (both % of cells that recovered and recovery time, p < 0.05). Additionally, the EGCG and combination reduced stress-mediated inflammation in HAPI rat microglial cells by attenuating LPS-induced nitrite release, inducible nitrous oxide synthase (iNOS) expression, and tumor necrosis factor-alpha (TNF-α) release (p < 0.05), but not cyclooxygenase-2 (COX-2) expression. Overall, broccoli sprouts (2 µM) and curcumin (1 µM) were not as effective as the EGCG or combination. Further research is needed to determine if dietary intervention with a variety of foods containing compounds such as those found in green tea, turmeric, or broccoli sprouts can play a role in reducing age-related CNS inflammation, microglial activation, and downstream signaling pathways that can lead to neuronal dysfunction. MDPI 2022-10-21 /pmc/articles/PMC9603949/ /pubmed/36293507 http://dx.doi.org/10.3390/ijms232012651 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fisher, Derek R. Zheng, Tong Bielinski, Donna F. Kelly, Megan E. Cahoon, Danielle S. Shukitt-Hale, Barbara Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title | Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title_full | Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title_fullStr | Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title_full_unstemmed | Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title_short | Phytochemical Combination Is More Effective than Individual Components in Reducing Stress Signaling in Rat Hippocampal Neurons and Microglia In Vitro |
title_sort | phytochemical combination is more effective than individual components in reducing stress signaling in rat hippocampal neurons and microglia in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603949/ https://www.ncbi.nlm.nih.gov/pubmed/36293507 http://dx.doi.org/10.3390/ijms232012651 |
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