Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury
The present study aimed to evaluate the role of diosmetin in alleviating advanced glycation end products (AGEs)-induced Alzheimer’s disease (AD)-like pathology and to clarify the action mechanisms. Before stimulation with AGEs (200 μg/mL), SH-SY5Y cells were treated with diosmetin (10 μmol/L), incre...
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MDPI AG
2022-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/11/2248 |
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| author | Mei Chou Lai Wayne Young Liu Shorong-Shii Liou I-Min Liu |
| author_facet | Mei Chou Lai Wayne Young Liu Shorong-Shii Liou I-Min Liu |
| author_sort | Mei Chou Lai |
| collection | DOAJ |
| description | The present study aimed to evaluate the role of diosmetin in alleviating advanced glycation end products (AGEs)-induced Alzheimer’s disease (AD)-like pathology and to clarify the action mechanisms. Before stimulation with AGEs (200 μg/mL), SH-SY5Y cells were treated with diosmetin (10 μmol/L), increasing cell viability. The induction of AGEs on the reactive oxygen species overproduction and downregulation of antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase, and catalase, were ameliorated by diosmetin. Amyloid precursor protein upregulation, accompanied by increased production of amyloid-β, caused by AGEs, was reversed by diosmetin. In the presence of diosmetin, not only β-site amyloid precursor protein cleaving enzyme1 expression was lowered, but the protein levels of insulin-degrading enzyme and neprilysin were elevated. Diosmetin protects SH-SY5Y cells from endoplasmic reticulum (ER) stress response to AGEs by suppressing ER stress-induced glucose regulated protein 78, thereby downregulating protein kinase R-like endoplasmic reticulum kinase, eukaryotic initiation factor 2 α, activating transcription factor 4, and C/EBP homologous protein. Diosmetin-pretreated cells had a lower degree of apoptotic DNA fragmentation; this effect may be associated with B-cell lymphoma (Bcl) 2 protein upregulation, Bcl-2-associated X protein downregulation, and decreased activities of caspase-12/-9/-3. The reversion of diosmetin on the AGEs-induced harmful effects was similar to that produced by pioglitazone. The peroxisome proliferator-activated receptor (PPAR)<i>γ</i> antagonist T0070907 (5 μmol/L) abolished the beneficial effects of diosmetin on AGEs-treated SH-SY5Y cells, indicating the involvement of PPAR<i>γ</i>. We conclude that diosmetin protects neuroblastoma cells against AGEs-induced ER injury via multiple mechanisms and may be a potential option for AD. |
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| language | English |
| last_indexed | 2024-03-10T01:00:31Z |
| publishDate | 2022-05-01 |
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| series | Nutrients |
| spelling | doaj.art-471350790db9436eb51543a04dbf6d652023-11-23T14:35:59ZengMDPI AGNutrients2072-66432022-05-011411224810.3390/nu14112248Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal InjuryMei Chou Lai0Wayne Young Liu1Shorong-Shii Liou2I-Min Liu3Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, TaiwanDepartment of Urology, Jen-Ai Hospital, Taichung 41265, TaiwanDepartment of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, TaiwanDepartment of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, TaiwanThe present study aimed to evaluate the role of diosmetin in alleviating advanced glycation end products (AGEs)-induced Alzheimer’s disease (AD)-like pathology and to clarify the action mechanisms. Before stimulation with AGEs (200 μg/mL), SH-SY5Y cells were treated with diosmetin (10 μmol/L), increasing cell viability. The induction of AGEs on the reactive oxygen species overproduction and downregulation of antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase, and catalase, were ameliorated by diosmetin. Amyloid precursor protein upregulation, accompanied by increased production of amyloid-β, caused by AGEs, was reversed by diosmetin. In the presence of diosmetin, not only β-site amyloid precursor protein cleaving enzyme1 expression was lowered, but the protein levels of insulin-degrading enzyme and neprilysin were elevated. Diosmetin protects SH-SY5Y cells from endoplasmic reticulum (ER) stress response to AGEs by suppressing ER stress-induced glucose regulated protein 78, thereby downregulating protein kinase R-like endoplasmic reticulum kinase, eukaryotic initiation factor 2 α, activating transcription factor 4, and C/EBP homologous protein. Diosmetin-pretreated cells had a lower degree of apoptotic DNA fragmentation; this effect may be associated with B-cell lymphoma (Bcl) 2 protein upregulation, Bcl-2-associated X protein downregulation, and decreased activities of caspase-12/-9/-3. The reversion of diosmetin on the AGEs-induced harmful effects was similar to that produced by pioglitazone. The peroxisome proliferator-activated receptor (PPAR)<i>γ</i> antagonist T0070907 (5 μmol/L) abolished the beneficial effects of diosmetin on AGEs-treated SH-SY5Y cells, indicating the involvement of PPAR<i>γ</i>. We conclude that diosmetin protects neuroblastoma cells against AGEs-induced ER injury via multiple mechanisms and may be a potential option for AD.https://www.mdpi.com/2072-6643/14/11/2248diosmetinAGEsAlzheimer’s diseaseSH-SY5Y cellsendoplasmic reticulum stressPPAR<i>γ</i> |
| spellingShingle | Mei Chou Lai Wayne Young Liu Shorong-Shii Liou I-Min Liu Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury Nutrients diosmetin AGEs Alzheimer’s disease SH-SY5Y cells endoplasmic reticulum stress PPAR<i>γ</i> |
| title | Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury |
| title_full | Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury |
| title_fullStr | Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury |
| title_full_unstemmed | Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury |
| title_short | Diosmetin Targeted at Peroxisome Proliferator-Activated Receptor Gamma Alleviates Advanced Glycation End Products Induced Neuronal Injury |
| title_sort | diosmetin targeted at peroxisome proliferator activated receptor gamma alleviates advanced glycation end products induced neuronal injury |
| topic | diosmetin AGEs Alzheimer’s disease SH-SY5Y cells endoplasmic reticulum stress PPAR<i>γ</i> |
| url | https://www.mdpi.com/2072-6643/14/11/2248 |
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