Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity
Abstract Amyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer’s disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identif...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00569-6 |
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| author | Deepali Singh Apurva Agrawal Chitra Mohinder Singh Singal Hriday Shanker Pandey Pankaj Seth Shiv Kumar Sharma |
| author_facet | Deepali Singh Apurva Agrawal Chitra Mohinder Singh Singal Hriday Shanker Pandey Pankaj Seth Shiv Kumar Sharma |
| author_sort | Deepali Singh |
| collection | DOAJ |
| description | Abstract Amyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer’s disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identification of compounds that can reduce or inhibit neuroinflammation. Here, we show that sinomenine, a compound present in a Chinese medicinal plant, Sinomenium acutum, inhibits oligomeric amyloid beta-induced production of reactive oxygen species (ROS), nitric oxide (NO) and inflammation-related molecules from astrocytic cells. The conditioned medium from oligomeric amyloid beta-treated astrocytic cells induces cell death in the hippocampal neuronal cells. Importantly, sinomenine inhibits this cell death. In addition, this compound has inhibitory effects on the production of ROS, NO and inflammation-related factors from oligomeric amyloid-beta treated human astrocytes. Finally, the conditioned medium from oligomeric amyloid beta-treated human astrocytes induces cell death in the primary culture of human neurons, which is inhibited by sinomenine. Thus, sinomenine inhibits amyloid beta-induced production of toxic factors from astrocytes, and confers protection to hippocampal neuronal cells as well as human neurons against indirect toxicity. The results suggest that this compound could provide beneficial effects in AD and other neurodegenerative conditions by reducing inflammation and neuronal cell death. |
| first_indexed | 2024-12-23T05:48:04Z |
| format | Article |
| id | doaj.art-496ddff650884c54b8f27b33a2af3062 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-23T05:48:04Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-496ddff650884c54b8f27b33a2af30622022-12-21T17:58:02ZengBMCMolecular Brain1756-66062020-03-0113111010.1186/s13041-020-00569-6Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicityDeepali Singh0Apurva Agrawal1Chitra Mohinder Singh Singal2Hriday Shanker Pandey3Pankaj Seth4Shiv Kumar Sharma5National Brain Research CentreNational Brain Research CentreNational Brain Research CentreNational Brain Research CentreNational Brain Research CentreNational Brain Research CentreAbstract Amyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer’s disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identification of compounds that can reduce or inhibit neuroinflammation. Here, we show that sinomenine, a compound present in a Chinese medicinal plant, Sinomenium acutum, inhibits oligomeric amyloid beta-induced production of reactive oxygen species (ROS), nitric oxide (NO) and inflammation-related molecules from astrocytic cells. The conditioned medium from oligomeric amyloid beta-treated astrocytic cells induces cell death in the hippocampal neuronal cells. Importantly, sinomenine inhibits this cell death. In addition, this compound has inhibitory effects on the production of ROS, NO and inflammation-related factors from oligomeric amyloid-beta treated human astrocytes. Finally, the conditioned medium from oligomeric amyloid beta-treated human astrocytes induces cell death in the primary culture of human neurons, which is inhibited by sinomenine. Thus, sinomenine inhibits amyloid beta-induced production of toxic factors from astrocytes, and confers protection to hippocampal neuronal cells as well as human neurons against indirect toxicity. The results suggest that this compound could provide beneficial effects in AD and other neurodegenerative conditions by reducing inflammation and neuronal cell death.http://link.springer.com/article/10.1186/s13041-020-00569-6Alzheimer’s diseaseAmyloid betaSinomenineNeurotoxicityNeuroinflammation |
| spellingShingle | Deepali Singh Apurva Agrawal Chitra Mohinder Singh Singal Hriday Shanker Pandey Pankaj Seth Shiv Kumar Sharma Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity Molecular Brain Alzheimer’s disease Amyloid beta Sinomenine Neurotoxicity Neuroinflammation |
| title | Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity |
| title_full | Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity |
| title_fullStr | Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity |
| title_full_unstemmed | Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity |
| title_short | Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity |
| title_sort | sinomenine inhibits amyloid beta induced astrocyte activation and protects neurons against indirect toxicity |
| topic | Alzheimer’s disease Amyloid beta Sinomenine Neurotoxicity Neuroinflammation |
| url | http://link.springer.com/article/10.1186/s13041-020-00569-6 |
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