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Mar. Drugs 2016, 14(3), 55; doi:10.3390/md14030055

Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent

1
Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA
2
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA
3
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: George Perry
Received: 29 January 2016 / Revised: 28 February 2016 / Accepted: 4 March 2016 / Published: 10 March 2016
(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)
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Abstract

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. View Full-Text
Keywords: Pseudopterogorgia elisabethae; octocoral; pseudopterosins; oxidative stress; Drosophila melanogaster; blood-brain barrier; neuromodulatory agent Pseudopterogorgia elisabethae; octocoral; pseudopterosins; oxidative stress; Drosophila melanogaster; blood-brain barrier; neuromodulatory agent
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Caplan, S.L.; Zheng, B.; Dawson-Scully, K.; White, C.A.; West, L.M. Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent. Mar. Drugs 2016, 14, 55.

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