Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease
Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/8302636 |
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| author | Dmitri Leonoudakis Anand Rane Suzanne Angeli Gordon J. Lithgow Julie K. Andersen Shankar J. Chinta |
| author_facet | Dmitri Leonoudakis Anand Rane Suzanne Angeli Gordon J. Lithgow Julie K. Andersen Shankar J. Chinta |
| author_sort | Dmitri Leonoudakis |
| collection | DOAJ |
| description | Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects in glial cells. Our results demonstrate that securinine significantly and dose-dependently suppressed the nitric oxide production in microglia and astrocytic cultures. In addition, securinine inhibited the activation of the inflammatory mediator NF-κB, as well as mitogen-activated protein kinases in lipopolysaccharide- (LPS-) stimulated BV2 cells. Additionally, securinine also inhibited interferon-γ- (IFN-γ-) induced nitric oxide levels and iNOS mRNA expression. Furthermore, conditioned media (CM) from securinine pretreated BV2 cells significantly reduced mesencephalic dopaminergic neurotoxicity compared with CM from LPS stimulated microglia. These findings suggest that securinine may be a potential candidate for the treatment of neurodegenerative diseases related to neuroinflammation. |
| format | Article |
| id | doaj-art-e8297fd24b1748928399fffe66af1127 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e8297fd24b1748928399fffe66af11272025-02-03T06:10:50ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/83026368302636Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s DiseaseDmitri Leonoudakis0Anand Rane1Suzanne Angeli2Gordon J. Lithgow3Julie K. Andersen4Shankar J. Chinta5Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USABuck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USAGlial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects in glial cells. Our results demonstrate that securinine significantly and dose-dependently suppressed the nitric oxide production in microglia and astrocytic cultures. In addition, securinine inhibited the activation of the inflammatory mediator NF-κB, as well as mitogen-activated protein kinases in lipopolysaccharide- (LPS-) stimulated BV2 cells. Additionally, securinine also inhibited interferon-γ- (IFN-γ-) induced nitric oxide levels and iNOS mRNA expression. Furthermore, conditioned media (CM) from securinine pretreated BV2 cells significantly reduced mesencephalic dopaminergic neurotoxicity compared with CM from LPS stimulated microglia. These findings suggest that securinine may be a potential candidate for the treatment of neurodegenerative diseases related to neuroinflammation.http://dx.doi.org/10.1155/2017/8302636 |
| spellingShingle | Dmitri Leonoudakis Anand Rane Suzanne Angeli Gordon J. Lithgow Julie K. Andersen Shankar J. Chinta Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease Mediators of Inflammation |
| title | Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease |
| title_full | Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease |
| title_fullStr | Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease |
| title_full_unstemmed | Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease |
| title_short | Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson’s Disease |
| title_sort | anti inflammatory and neuroprotective role of natural product securinine in activated glial cells implications for parkinson s disease |
| url | http://dx.doi.org/10.1155/2017/8302636 |
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