Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder
Abstract The hippocampus has been implicated in the pathogenesis of insomnia disorder (ID) and the purpose of this study was to investigate the neuroprotective mechanism of the natural flavone Kurarinone (Kur) on hippocampal neurotoxicity as a potential treatment of ID. The effect of Kur on hippocam...
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1132 |
| _version_ | 1797658888097497088 |
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| author | Guoqing Wu Yanyan Wu |
| author_facet | Guoqing Wu Yanyan Wu |
| author_sort | Guoqing Wu |
| collection | DOAJ |
| description | Abstract The hippocampus has been implicated in the pathogenesis of insomnia disorder (ID) and the purpose of this study was to investigate the neuroprotective mechanism of the natural flavone Kurarinone (Kur) on hippocampal neurotoxicity as a potential treatment of ID. The effect of Kur on hippocampal neuronal cell (HNC) viability and apoptosis were assessed by Cell counting kit‐8 (CCK‐8) assay and flow cytometry, respectively. Then, the effect of Kur on β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1), brain‐derived neurotrophic factor (BDNF), and phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) phosphorylation level were measured by Western blot. Further, SwissTargetPrediction analysis and molecular docking experiments were used to detect a potential target of Kur. Then, the p‐chlorophenylalanine (PCPA) model was established in vivo to further study the effect of BACE1 expression on Kur and HNC. As a result, HNC viability was only significantly decreased by 2 μM of Kur. Kur reversed the impacts of corticosterone upon inhibiting viability (0.25–1 μM), PI3K (0.5–1 μM)/AKT phosphorylation, and BDNF (1 μM) level, and enhancing the apoptosis (0.25–1 μM) and BACE1 expression (1 μM) in HNCs. BACE1 was a potential target of Kur. Notably, Kur (150 mg/kg) attenuated PCPA‐induced upregulation of BACE1 expression in rat hippocampal tissues as ZRAS (0.8 g/kg). The effects of Kur (1 μM) on corticosterone‐treated HNCs were reversed by BACE1 overexpression. Collectively, Kur downregulates BACE1 level to activate PI3K/AKT, thereby attenuating corticosterone‐induced toxicity in HNCs, indicating that Kur possibly exerted a neuroprotective effect, which providing a new perspective for the treatment of insomnia disorders. |
| first_indexed | 2024-03-11T18:05:49Z |
| format | Article |
| id | doaj.art-22c8d7a68d134e38828c248b07867754 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-11T18:05:49Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-22c8d7a68d134e38828c248b078677542023-10-17T07:30:29ZengWileyPharmacology Research & Perspectives2052-17072023-10-01115n/an/a10.1002/prp2.1132Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorderGuoqing Wu0Yanyan Wu1Department of Medicine Tongde Hospital of Zhejiang Province Hangzhou ChinaDepartment of Medicine Tongde Hospital of Zhejiang Province Hangzhou ChinaAbstract The hippocampus has been implicated in the pathogenesis of insomnia disorder (ID) and the purpose of this study was to investigate the neuroprotective mechanism of the natural flavone Kurarinone (Kur) on hippocampal neurotoxicity as a potential treatment of ID. The effect of Kur on hippocampal neuronal cell (HNC) viability and apoptosis were assessed by Cell counting kit‐8 (CCK‐8) assay and flow cytometry, respectively. Then, the effect of Kur on β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1), brain‐derived neurotrophic factor (BDNF), and phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (AKT) phosphorylation level were measured by Western blot. Further, SwissTargetPrediction analysis and molecular docking experiments were used to detect a potential target of Kur. Then, the p‐chlorophenylalanine (PCPA) model was established in vivo to further study the effect of BACE1 expression on Kur and HNC. As a result, HNC viability was only significantly decreased by 2 μM of Kur. Kur reversed the impacts of corticosterone upon inhibiting viability (0.25–1 μM), PI3K (0.5–1 μM)/AKT phosphorylation, and BDNF (1 μM) level, and enhancing the apoptosis (0.25–1 μM) and BACE1 expression (1 μM) in HNCs. BACE1 was a potential target of Kur. Notably, Kur (150 mg/kg) attenuated PCPA‐induced upregulation of BACE1 expression in rat hippocampal tissues as ZRAS (0.8 g/kg). The effects of Kur (1 μM) on corticosterone‐treated HNCs were reversed by BACE1 overexpression. Collectively, Kur downregulates BACE1 level to activate PI3K/AKT, thereby attenuating corticosterone‐induced toxicity in HNCs, indicating that Kur possibly exerted a neuroprotective effect, which providing a new perspective for the treatment of insomnia disorders.https://doi.org/10.1002/prp2.1132BACE1hippocampal neuron cytotoxicityinsomniaKurarinonePI3K/AKT signaling |
| spellingShingle | Guoqing Wu Yanyan Wu Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder Pharmacology Research & Perspectives BACE1 hippocampal neuron cytotoxicity insomnia Kurarinone PI3K/AKT signaling |
| title | Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder |
| title_full | Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder |
| title_fullStr | Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder |
| title_full_unstemmed | Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder |
| title_short | Neuroprotective effect of Kurarinone against corticosterone‐induced cytotoxicity on rat hippocampal neurons by targeting BACE1 to activate P13K–AKT signaling – A potential treatment in insomnia disorder |
| title_sort | neuroprotective effect of kurarinone against corticosterone induced cytotoxicity on rat hippocampal neurons by targeting bace1 to activate p13k akt signaling a potential treatment in insomnia disorder |
| topic | BACE1 hippocampal neuron cytotoxicity insomnia Kurarinone PI3K/AKT signaling |
| url | https://doi.org/10.1002/prp2.1132 |
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