Quinolones Modulate Ghrelin Receptor Signaling: Potential for a Novel Small Molecule Scaffold in the Treatment of Cachexia.

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.

A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo.

Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

Protein and amino acid composition of select wild legume species of tribe Fabeae.

The nutritional characteristics of seed proteins of 50 Spanish wild taxa of Lathyrus, Lens, Pisum and Vicia have been compared. The highest average protein richness and the in vitro protein digestibility have been observed in the genus Vicia and Lens, respectively, whereas the genus Pisum showed the lowest protein-digestibility corrected amino acid score. Using the K-means algorithm three clearly distinguished groups of taxa have been established in relation to their essential amino acid contents, protein richness, digestibility and nutritional parameters. The most adequate protein profile was observed in the taxa of group 1. This group includes four taxa of genus Lathyrus and nine taxa of genus Vicia. It should be noted that seven of the thirteen taxa included in this group have never been used as crops.

Extrusion Conditions and Amylose Content Affect Physicochemical Properties of Extrudates Obtained from Brown Rice Grains.

The utilization of whole grains in food formulations is nowadays recommended. Extrusion cooking allows obtaining precooked cereal products and a wide range of ready-to-eat foods. Two rice varieties having different amylose content (Fortuna 16% and Paso 144, 27%) were extruded using a Brabender single screw extruder. Factorial experimental design was used to study the effects of extrusion temperature (160, 175, and 190°C) and grits moisture content (14%, 16.5%, and 19%) on extrudate properties. Specific mechanical energy consumption (SMEC), radial expansion (E), specific volume (SV), water absorption (WA), and solubility (S) were determined on each extrudate sample. In general, Fortuna variety showed higher values of SMEC and S (703-409 versus 637-407 J/g; 33.0-21.0 versus 20.1-11.0%, resp.) than those of Paso 144; on the contrary SV (8.64-3.47 versus 8.27-4.53 mL/g) and WA tended to be lower (7.7-5.1 versus 8.4-6.6 mL/g). Both varieties showed similar values of expansion rate (3.60-2.18). Physical characteristics depended on extrusion conditions and rice variety used. The degree of cooking reached by Paso rice samples was lower than that obtained for Fortuna. It is suggested that the presence of germ and bran interfered with the cooking process, decreasing friction level and broadening residence time distribution.

Nutritional characteristics of seed proteins in 28 Vicia species (Fabaceae) from Southern Spain.

The study of local plants could provide useful data for the possible development of future crops with good nutritional and functional properties. The nutritional characteristics of the seed proteins of 28 Vicia species (31 taxa) (Fabaceae) from Spain were studied. Protein contents in studied Vicia ranged from 20.1% in V. articulata to 32% in V. pyrenaica. V. altissima, which is only deficient in Trp, showed the most balanced amino acid composition, while the remaining taxa were limiting in Met, Cys, and Trp. In vitro protein digestibility (IVPD) ranged from 78% in V. incana to 86.3% in V. hirsuta. In addition to the amino acid composition and IVPD, other nutritional parameters, such as amino acid score, biological value, protein efficiency ratio, or protein digestibility corrected amino acid score, were studied. Results confirm the interest of studying wild populations of cultivated and non cultivated Vicia species as potentially interesting sources of seeds with good nutritional characteristics.