The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice
Background: Despite considerable advances in pharmacotherapy, more effective therapeutic interventions for aging-related neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), remain limited. Urolithin B (UB), one of the major subcategories of urolithins (microbiota metabolites) found...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/f998bb5703aa49e3bdbf7aa54a5a598e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:f998bb5703aa49e3bdbf7aa54a5a598e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:f998bb5703aa49e3bdbf7aa54a5a598e2021-11-15T06:59:36ZThe Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice1663-981210.3389/fphar.2021.768097https://doaj.org/article/f998bb5703aa49e3bdbf7aa54a5a598e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.768097/fullhttps://doaj.org/toc/1663-9812Background: Despite considerable advances in pharmacotherapy, more effective therapeutic interventions for aging-related neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), remain limited. Urolithin B (UB), one of the major subcategories of urolithins (microbiota metabolites) found in various tissues after ellagitannin consumption, has been shown to possess antioxidant, anti-inflammatory, and antiapoptotic effects. However, the neuroprotective effect of UB on brain aging in mice and its potential mechanisms were still unknown.Methods: In the current research, we first assessed the ameliorative effects of UB on oxidative injury and apoptosis induced by H2O2 in neuro-2a cells. Then a subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of UB. The capacity of memory and learning, alterations of hippocampus histology and corresponding molecular mechanisms were all evaluated.Results: The D-gal-induced accelerated aging model in vivo demonstrated that UB could significantly ameliorate deficits in learning and memory by inhibiting the accumulation of advanced glycation end products (AGEs) and elevating the expression and activity of Cu, Zn-SOD and CAT. Furthermore, UB downregulated the c-Jun N-terminal kinase (JNK) signaling pathway and prevented cytochrome c release from isolated mitochondria, thereby inhibiting neuronal apoptosis during the aging process. More importantly, UB stimulation of aging mice activated ERK and phosphoinositide 3-kinase (PI3K), leading to neuronal survival along with Akt and p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and activation.Conclusion: In summary, UB effectively alleviated cognitive deficits and ameliorated brain aging-related conditions and could be considered a healthcare product to prevent aging-associated NDs such as AD.Peng ChenFuchao ChenFuchao ChenJiexin LeiGaohua WangBenhong ZhouBenhong ZhouFrontiers Media S.A.articleUBd-Galaginglearning and memoryapoptosisPI3K pathwayTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
UB d-Gal aging learning and memory apoptosis PI3K pathway Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
UB d-Gal aging learning and memory apoptosis PI3K pathway Therapeutics. Pharmacology RM1-950 Peng Chen Fuchao Chen Fuchao Chen Jiexin Lei Gaohua Wang Benhong Zhou Benhong Zhou The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| description |
Background: Despite considerable advances in pharmacotherapy, more effective therapeutic interventions for aging-related neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), remain limited. Urolithin B (UB), one of the major subcategories of urolithins (microbiota metabolites) found in various tissues after ellagitannin consumption, has been shown to possess antioxidant, anti-inflammatory, and antiapoptotic effects. However, the neuroprotective effect of UB on brain aging in mice and its potential mechanisms were still unknown.Methods: In the current research, we first assessed the ameliorative effects of UB on oxidative injury and apoptosis induced by H2O2 in neuro-2a cells. Then a subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of UB. The capacity of memory and learning, alterations of hippocampus histology and corresponding molecular mechanisms were all evaluated.Results: The D-gal-induced accelerated aging model in vivo demonstrated that UB could significantly ameliorate deficits in learning and memory by inhibiting the accumulation of advanced glycation end products (AGEs) and elevating the expression and activity of Cu, Zn-SOD and CAT. Furthermore, UB downregulated the c-Jun N-terminal kinase (JNK) signaling pathway and prevented cytochrome c release from isolated mitochondria, thereby inhibiting neuronal apoptosis during the aging process. More importantly, UB stimulation of aging mice activated ERK and phosphoinositide 3-kinase (PI3K), leading to neuronal survival along with Akt and p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and activation.Conclusion: In summary, UB effectively alleviated cognitive deficits and ameliorated brain aging-related conditions and could be considered a healthcare product to prevent aging-associated NDs such as AD. |
| format |
article |
| author |
Peng Chen Fuchao Chen Fuchao Chen Jiexin Lei Gaohua Wang Benhong Zhou Benhong Zhou |
| author_facet |
Peng Chen Fuchao Chen Fuchao Chen Jiexin Lei Gaohua Wang Benhong Zhou Benhong Zhou |
| author_sort |
Peng Chen |
| title |
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| title_short |
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| title_full |
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| title_fullStr |
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| title_full_unstemmed |
The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice |
| title_sort |
gut microbiota metabolite urolithin b improves cognitive deficits by inhibiting cyt c-mediated apoptosis and promoting the survival of neurons through the pi3k pathway in aging mice |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/f998bb5703aa49e3bdbf7aa54a5a598e |
| work_keys_str_mv |
AT pengchen thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT fuchaochen thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT fuchaochen thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT jiexinlei thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT gaohuawang thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT benhongzhou thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT benhongzhou thegutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT pengchen gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT fuchaochen gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT fuchaochen gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT jiexinlei gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT gaohuawang gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT benhongzhou gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice AT benhongzhou gutmicrobiotametaboliteurolithinbimprovescognitivedeficitsbyinhibitingcytcmediatedapoptosisandpromotingthesurvivalofneuronsthroughthepi3kpathwayinagingmice |
| _version_ |
1718428532608073728 |