Natural Xanthone α-Mangostin Inhibits LPS-Induced Microglial Inflammatory Responses and Memory Impairment by Blocking the TAK1/NF-κB Signaling Pathway
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
SCOPE: The effect of α-mangostin (α-M), a polyphenolic xanthone isolated from mangostin, on lipopolysaccharide (LPS)-induced microglial activation and memory impairment is explored. The possible underlying mechanisms are also investigated.
METHODS AND RESULTS: Cytokine production and activation of transforming growth factor activated kinase-1 (TAK1) and nuclear factor-κB (NF-κB) are detected by enzyme-linked immunosorbent assay (ELISA) or Western blot. Microglial migration and phagocytosis are evaluated with scratch wound-healing assay and phagocytosis of fluorescent latex beads, respectively. Learning and memory abilities of mice are evaluated with the Morris water maze test. The nanomolar (100-500 nm) α-M suppresses LPS-induced pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) expression in microglia. It also inhibits LPS-induced microglial migration and phagocytosis. α-M rescues LPS-caused, microglia-mediated neuronal dendritic damage. Moreover, α-M represses LPS-induced toll-like receptor 4 (TLR4) expression and activation of TAK1 and NF-κB. In a mouse neuroinflammation model, α-M (50 mg kg-1 day-1 ) shows obvious anti-neuroinflammatory, neuroprotective, and memory-improving effects in vivo.
CONCLUSION: α-M inhibits microglia-mediated neuroinflammation and prevents neurotoxicity and memory impairment from inflammatory damage. These results indicate that α-M has great potential to be used as a nutritional preventive strategy for neuroinflammation-related neurodegenerative disorders such as Alzheimer's disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
Molecular nutrition & food research - 64(2020), 14 vom: 16. Juli, Seite e2000096 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guan, Huifeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2021 Date Revised 26.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/mnfr.202000096 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310863260 |
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| 245 | 1 | 0 | |a Natural Xanthone α-Mangostin Inhibits LPS-Induced Microglial Inflammatory Responses and Memory Impairment by Blocking the TAK1/NF-κB Signaling Pathway |
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| 500 | |a Date Completed 26.07.2021 | ||
| 500 | |a Date Revised 26.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a SCOPE: The effect of α-mangostin (α-M), a polyphenolic xanthone isolated from mangostin, on lipopolysaccharide (LPS)-induced microglial activation and memory impairment is explored. The possible underlying mechanisms are also investigated | ||
| 520 | |a METHODS AND RESULTS: Cytokine production and activation of transforming growth factor activated kinase-1 (TAK1) and nuclear factor-κB (NF-κB) are detected by enzyme-linked immunosorbent assay (ELISA) or Western blot. Microglial migration and phagocytosis are evaluated with scratch wound-healing assay and phagocytosis of fluorescent latex beads, respectively. Learning and memory abilities of mice are evaluated with the Morris water maze test. The nanomolar (100-500 nm) α-M suppresses LPS-induced pro-inflammatory cytokine production and inducible nitric oxide synthase (iNOS) expression in microglia. It also inhibits LPS-induced microglial migration and phagocytosis. α-M rescues LPS-caused, microglia-mediated neuronal dendritic damage. Moreover, α-M represses LPS-induced toll-like receptor 4 (TLR4) expression and activation of TAK1 and NF-κB. In a mouse neuroinflammation model, α-M (50 mg kg-1 day-1 ) shows obvious anti-neuroinflammatory, neuroprotective, and memory-improving effects in vivo | ||
| 520 | |a CONCLUSION: α-M inhibits microglia-mediated neuroinflammation and prevents neurotoxicity and memory impairment from inflammatory damage. These results indicate that α-M has great potential to be used as a nutritional preventive strategy for neuroinflammation-related neurodegenerative disorders such as Alzheimer's disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Luo, Shenying |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yangdan |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Yiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Baichuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongzhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Juan |e verfasserin |4 aut | |
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