title: Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent.
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.
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA. scaplan4@fau.edu.
authors.forename: Stacee Lee
authors.initials: SL
authors.lastname: Caplan
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA. bozhengjob@gmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA. ken.dawson-scully@fau.edu.
authors.forename: Ken
authors.initials: K
authors.lastname: Dawson-Scully
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA. cwhite@rx.uga.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: White
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA. lwest@fau.edu.|Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA. lwest@fau.edu.
authors.forename: Lyndon M
authors.initials: LM
authors.lastname: West
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004331:Drosophila melanogaster; D055808:Drug Discovery / Q000379:methods; D006027:Glycosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D004224:Diterpenes; D006027:Glycosides; D018377:Neurotransmitter Agents; C049922:pseudopterosins
keywords: Drosophila melanogaster; Pseudopterogorgia elisabethae; blood-brain barrier; neuromodulatory agent; octocoral; oxidative stress; pseudopterosins