David A. Gragirenes Delgado1, María F. Acevedo Kury1, Gabriela M. Ramírez Renta1, Geraldine M. Ortiz Sosa2, Aniel J. Rivera Arzola3, Janiennid Alicea Tirado3, Ricardo M. Cruz Sánchez1, Lymelsie Aponte Ramos4, Adrián E. González Santiago2, Grayce E. Dyer Levin5, Eduardo Caro Díaz5, Ricardo Chiesa1​
1Department of Biology, 2Department of Natural Sciences, 3Department of Chemistry, ​4Department of Social Sciences, University of Puerto Rico, Cayey, Puerto Rico, and 5UPR – Medical Science Campus

Introduction: Surveys show that one-third of the population is affected by an anxiety disorder. These are mostly treated with benzodiazepines which can induce dependence disorders through tolerance and resistance mechanisms. This highlights the need for safer and more effective anxiolytic drugs. Recently, marine natural products have proven to be a rich chemical space for drug discovery and development. Specifically, tropical marine algae produce a wide range of metabolites with diverse biological activity, including neuroprotection. We propose to study the anxiolytic effects of natural products derived from tropical marine brown algae using Drosophila melanogaster as a model. Our research aims to chemically characterize brown algae extracts, use extracts for anxiety-related behavioral tests, and identify the chemical components responsible for the anxiolytic activity.

Methods: The methodology consists of performing Open Field Tests (OFT) using young adult flies to compare the behavior between the negative control group (not exposed to extracts) and the experimental groups, that include acute expositions (6 hours) and chronic expositions (oviposition to adulthood) to algae extracts. The parameter measured was the distance each fly traveled from the center of the Open Field Arena to the walls.

Results: We have previously reported anxiolytic effects in Drosophila after the chronic administration of the crude organic extract of Stypopodium zonale using OFT.
Statistically significant anxiolytic effects were also obtained for Dictyota cervicornis, Padina boergesenii, and Symploca in chronic expositions, although no anxiolytic effects were observed for Ulva and Sargassum sp. Recent data has proven that the crude organic extracts from Stypopodium zonale and Padina boergesenii exhibited anxiolytic effects in acute expositions that are comparable to the effect of diazepam, a benzodiazepine used as our positive control.

Conclusion: Our research represents an unprecedented approach to anxiolytic drug discovery as it improves our understanding of Puerto Rico’s marine algae and their natural products’ chemo-diversity.

Acknowledgements
Mentor/Principal Investigator (PI): Dr. Ricardo Chiesa, University of Puerto Rico in Cayey, Department of Biology
Co-PI: Dr. Eduardo Caro, School of Pharmacy of University of Puerto Rico, Medical Science Campus

Collaborators
Dr. Chad Lozada, Department of Biology, UPR Cayey
Dr. María De Jesús, Department of Biology, UPR Cayey

Funding and Support
Puerto Rico Science, Technology, and Research Trust- CATALYZER Grant
Office of the Dean of Academic Affairs- UPR Cayey
FIDI funds (Institutional Funds for Research Development)
Interdisciplinary Research Institute – UPR Cayey
Puerto Rico-INBRE
Translational Proteomics Center Core
Facility at the Comprehensive Cancer Center, Puerto Rico Medical Center.
Puerto Rico – Louis Stoke Alliance for Minority