| Autor: |
Torres-Fuentes C; APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland. ctorresfuentes@ucdavis.edu., Pastor-Cavada E; APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland. elenapastorcavada@gmail.com., Cano R; School of Chemistry and the Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork, T12 YT20 Cork, Ireland. rafael.canom@uam.es., Kandil D; Food for Health Ireland, University College Cork, T12 YT20 Cork, Ireland. dkandil@ucc.ie.; Department of Anatomy and Neuroscience, University College Cork, T12 YT20 Cork, Ireland. dkandil@ucc.ie., Shanahan R; School of Chemistry and the Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork, T12 YT20 Cork, Ireland. rachelshanahan91@gmail.com., Juan R; Plant Biology and Ecology Department, Seville University, 41012 Seville, Spain. rjuan@us.es., Shaban H; Food for Health Ireland, University College Cork, T12 YT20 Cork, Ireland. hamdy.shaban@gmx.ch., McGlacken GP; School of Chemistry and the Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork, T12 YT20 Cork, Ireland. g.mcglacken@ucc.ie., Schellekens H; APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland. h.schellekens@ucc.ie.; Food for Health Ireland, University College Cork, T12 YT20 Cork, Ireland. h.schellekens@ucc.ie.; Department of Anatomy and Neuroscience, University College Cork, T12 YT20 Cork, Ireland. h.schellekens@ucc.ie. |
| Abstrakt: |
Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders. |
