Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent
Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of thera...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2016-03-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/14/3/55 |
| _version_ | 1828117837326057472 |
|---|---|
| author | Stacee Lee Caplan Bo Zheng Ken Dawson-Scully Catherine A. White Lyndon M. West |
| author_facet | Stacee Lee Caplan Bo Zheng Ken Dawson-Scully Catherine A. White Lyndon M. West |
| author_sort | Stacee Lee Caplan |
| collection | DOAJ |
| description | Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent. |
| first_indexed | 2024-04-11T13:20:52Z |
| format | Article |
| id | doaj.art-f865657df25b4b2395eb01550ec170be |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:20:52Z |
| publishDate | 2016-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-f865657df25b4b2395eb01550ec170be2022-12-22T04:22:12ZengMDPI AGMarine Drugs1660-33972016-03-011435510.3390/md14030055md14030055Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory AgentStacee Lee Caplan0Bo Zheng1Ken Dawson-Scully2Catherine A. White3Lyndon M. West4Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USADepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USADepartment of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USADepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USADepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USANatural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent.http://www.mdpi.com/1660-3397/14/3/55Pseudopterogorgia elisabethaeoctocoralpseudopterosinsoxidative stressDrosophila melanogasterblood-brain barrierneuromodulatory agent |
| spellingShingle | Stacee Lee Caplan Bo Zheng Ken Dawson-Scully Catherine A. White Lyndon M. West Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent Marine Drugs Pseudopterogorgia elisabethae octocoral pseudopterosins oxidative stress Drosophila melanogaster blood-brain barrier neuromodulatory agent |
| title | Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent |
| title_full | Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent |
| title_fullStr | Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent |
| title_full_unstemmed | Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent |
| title_short | Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent |
| title_sort | pseudopterosin a protection of synaptic function and potential as a neuromodulatory agent |
| topic | Pseudopterogorgia elisabethae octocoral pseudopterosins oxidative stress Drosophila melanogaster blood-brain barrier neuromodulatory agent |
| url | http://www.mdpi.com/1660-3397/14/3/55 |
| work_keys_str_mv | AT staceeleecaplan pseudopterosinaprotectionofsynapticfunctionandpotentialasaneuromodulatoryagent AT bozheng pseudopterosinaprotectionofsynapticfunctionandpotentialasaneuromodulatoryagent AT kendawsonscully pseudopterosinaprotectionofsynapticfunctionandpotentialasaneuromodulatoryagent AT catherineawhite pseudopterosinaprotectionofsynapticfunctionandpotentialasaneuromodulatoryagent AT lyndonmwest pseudopterosinaprotectionofsynapticfunctionandpotentialasaneuromodulatoryagent |