In Vitro and In Silico Characterization of G-Protein Coupled Receptor (GPCR) Targets of Phlorofucofuroeckol-A and Dieckol

Phlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorotannins is lacking. This study explores prime GPCR targets of the two phlorotannins. In silico proteocheminformatics modeling predicted twenty major protein targets and in vitro functional assays showed a good agonist effect at the α2C adrenergic receptor (α2CAR) and an antagonist effect at the adenosine 2A receptor (A2AR), δ-opioid receptor (δ-OPR), glucagon-like peptide-1 receptor (GLP-1R), and 5-hydroxytryptamine 1A receptor (5-TH1AR) of both phlorotannins. Besides, dieckol showed an antagonist effect at the vasopressin 1A receptor (V1AR) and PFF-A showed a promising agonist effect at the cannabinoid 1 receptor and an antagonist effect at V1AR. In silico molecular docking simulation enabled us to investigate and identify distinct binding features of these phlorotannins to the target proteins. The docking results suggested that dieckol and PFF-A bind to the crystal structures of the proteins with good affinity involving key interacting amino acid residues comparable to reference ligands. Overall, the present study suggests α2CAR, A2AR, δ-OPR, GLP-1R, 5-TH1AR, CB1R, and V1AR as prime receptor targets of dieckol and PFF-A.

Neural correlates of mating system diversity: oxytocin and vasopressin receptor distributions in monogamous and non-monogamous Eulemur

Contemporary theory that emphasizes the roles of oxytocin and vasopressin in mammalian sociality has been shaped by seminal vole research that revealed interspecific variation in neuroendocrine circuitry by mating system. However, substantial challenges exist in interpreting and translating these rodent findings to other mammalian groups, including humans, making research on nonhuman primates crucial. Both monogamous and non-monogamous species exist within Eulemur, a genus of strepsirrhine primate, offering a rare opportunity to broaden a comparative perspective on oxytocin and vasopressin neurocircuitry with increased evolutionary relevance to humans. We performed oxytocin and arginine vasopressin 1a receptor autoradiography on 12 Eulemur brains from seven closely related species to (1) characterize receptor distributions across the genus, and (2) examine differences between monogamous and non-monogamous species in regions part of putative “pair-bonding circuits”. We find some binding patterns across Eulemur reminiscent of olfactory-guided rodents, but others congruent with more visually oriented anthropoids, consistent with lemurs occupying an ‘intermediary’ evolutionary niche between haplorhine primates and other mammalian groups. We find little evidence of a “pair-bonding circuit” in Eulemur akin to those proposed in previous rodent or primate research. Mapping neuropeptide receptors in these nontraditional species questions existing assumptions and informs proposed evolutionary explanations about the biological bases of monogamy.