Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation

Introduction Nucleotide-binding and oligomerization domain like receptors protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1β secretion plays an important role in the progression of Alzheimer’s disease (AD). Curcumin has been shown to improve cognitive impairment and learning ability of AD m...

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Autores principales:	Qiang Shi, Ying-ying Zheng, Le Wang, Yi-dong Xue, Yan-ling Yang
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/2308facc3475432dbcdda9ca52d4b6ab
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spelling	oai:doaj.org-article:2308facc3475432dbcdda9ca52d4b6ab2021-12-02T07:34:51ZCurcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation2058-739210.1177/20587392211058615https://doaj.org/article/2308facc3475432dbcdda9ca52d4b6ab2021-11-01T00:00:00Zhttps://doi.org/10.1177/20587392211058615https://doaj.org/toc/2058-7392Introduction Nucleotide-binding and oligomerization domain like receptors protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1β secretion plays an important role in the progression of Alzheimer’s disease (AD). Curcumin has been shown to improve cognitive impairment and learning ability of AD mice by reducing IL-1β secretion. However, its exact mechanism of action remains unclear. In the present study, we explored the relationship between the neuroprotective effect of curcumin and activation of the NLRP3 inflammasome pathway. Methods BV2 cells were primed with 500 ng/mL lipopolysaccharide (LPS) for 4 h and subsequently treated with 50 μM Aβ 25-35 for 24 h or pretreated with 2.5–10 μM curcumin for 4 h and exposed to 50 μM Aβ 25-35 for 24 h. The effects of curcumin and Aβ 25-35 were assessed by the CCK8 assay. ELISA was used for the detection of IL-1β, IL-6, and tumor necrosis factor (TNF)-α levels in the supernatant of the cell culture medium. The viability of SH-SY5Y cells, which were incubated with conditioned medium (CM) was assessed using the CCK8 assay. The percentage of apoptotic SH-SY5Y cells incubated with CM was assessed using Annexin V-FITC/PI staining flow cytometry analysis. The expression levels of NLRP3, caspase-1 and IL-1β were observed by western blot and immunofluorescence staining analyses; the mRNA levels of nlrp3, caspase-1 and IL-1β were analyzed using qRT-PCR. Results Low (2.5 μM), medium (5 μM), and high (10 μM) concentrations of curcumin and 50 μM Aβ 25-35 were used to perform the experiments in the present study. Curcumin attenuated the IL-1β, IL-6, and TNF-α release and increased SH-SY5Y cell activity, while decreasing the apoptotic percentage of SH-SY5Y cells using Aβ 25-35 for cell stimulation ( p < 0.05). Furthermore, curcumin inhibited the expression of NLRP3, caspase-1 and IL-1β and nlrp3 in BV-2 cells ( p < 0.05), However, curcumin did not affect the expression levels of caspase-1 and IL-1β ( p > 0.05) Conclusion Overall, the data indicated that curcumin is a promising neuroprotective agent for suppressing neuroinflammation by inhibiting the NLRP3 inflammasome pathway.Qiang ShiYing-ying ZhengLe WangYi-dong XueYan-ling YangSAGE PublishingarticleMedicineRENEuropean Journal of Inflammation, Vol 19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Qiang Shi Ying-ying Zheng Le Wang Yi-dong Xue Yan-ling Yang Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
description	Introduction Nucleotide-binding and oligomerization domain like receptors protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1β secretion plays an important role in the progression of Alzheimer’s disease (AD). Curcumin has been shown to improve cognitive impairment and learning ability of AD mice by reducing IL-1β secretion. However, its exact mechanism of action remains unclear. In the present study, we explored the relationship between the neuroprotective effect of curcumin and activation of the NLRP3 inflammasome pathway. Methods BV2 cells were primed with 500 ng/mL lipopolysaccharide (LPS) for 4 h and subsequently treated with 50 μM Aβ 25-35 for 24 h or pretreated with 2.5–10 μM curcumin for 4 h and exposed to 50 μM Aβ 25-35 for 24 h. The effects of curcumin and Aβ 25-35 were assessed by the CCK8 assay. ELISA was used for the detection of IL-1β, IL-6, and tumor necrosis factor (TNF)-α levels in the supernatant of the cell culture medium. The viability of SH-SY5Y cells, which were incubated with conditioned medium (CM) was assessed using the CCK8 assay. The percentage of apoptotic SH-SY5Y cells incubated with CM was assessed using Annexin V-FITC/PI staining flow cytometry analysis. The expression levels of NLRP3, caspase-1 and IL-1β were observed by western blot and immunofluorescence staining analyses; the mRNA levels of nlrp3, caspase-1 and IL-1β were analyzed using qRT-PCR. Results Low (2.5 μM), medium (5 μM), and high (10 μM) concentrations of curcumin and 50 μM Aβ 25-35 were used to perform the experiments in the present study. Curcumin attenuated the IL-1β, IL-6, and TNF-α release and increased SH-SY5Y cell activity, while decreasing the apoptotic percentage of SH-SY5Y cells using Aβ 25-35 for cell stimulation ( p < 0.05). Furthermore, curcumin inhibited the expression of NLRP3, caspase-1 and IL-1β and nlrp3 in BV-2 cells ( p < 0.05), However, curcumin did not affect the expression levels of caspase-1 and IL-1β ( p > 0.05) Conclusion Overall, the data indicated that curcumin is a promising neuroprotective agent for suppressing neuroinflammation by inhibiting the NLRP3 inflammasome pathway.
format	article
author	Qiang Shi Ying-ying Zheng Le Wang Yi-dong Xue Yan-ling Yang
author_facet	Qiang Shi Ying-ying Zheng Le Wang Yi-dong Xue Yan-ling Yang
author_sort	Qiang Shi
title	Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
title_short	Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
title_full	Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
title_fullStr	Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
title_full_unstemmed	Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation
title_sort	curcumin suppresses neuroinflammation to protect neurons by preventing nlrp3 inflammasome activation
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/2308facc3475432dbcdda9ca52d4b6ab
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_version_	1718399325029007360

Curcumin suppresses neuroinflammation to protect neurons by preventing NLRP3 inflammasome activation

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