title: Effects of pregnane glycosides on food intake depend on stimulation of the melanocortin pathway and BDNF in an animal model.
abstract: Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.
authors: Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina 28081, United States. komarnytsky@ncsu.edu
authors: Slavko
authors: S
authors: Komarnytsky
authors: Debora
authors: D
authors: Esposito
authors: Thirumurugan
authors: T
authors: Rathinasabapathy
authors: Alexander
authors: A
authors: Poulev
authors: Ilya
authors: I
authors: Raskin
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects; D031108:Asclepias / Q000737:chemistry*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004435:Eating / Q000187:drug effects*; D005260:Female; D006027:Glycosides / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D023421:Models, Animal; D010936:Plant Extracts / Q000008:administration & dosage*; D011278:Pregnanes / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006027:Glycosides; D053486:Melanocortins; D010936:Plant Extracts; D011278:Pregnanes; C574437:pregnane glycoside