PMID- 23308358 OWN - NLM STAT- MEDLINE DCOM- 20131203 LR - 20211021 IS - 1520-5118 (Electronic) IS - 0021-8561 (Print) IS - 0021-8561 (Linking) VI - 61 IP - 8 DP - 2013 Feb 27 TI - Effects of pregnane glycosides on food intake depend on stimulation of the melanocortin pathway and BDNF in an animal model. PG - 1841-9 LID - 10.1021/jf3033649 [doi] AB - 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. FAU - Komarnytsky, Slavko AU - Komarnytsky S AD - Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina 28081, United States. komarnytsky@ncsu.edu FAU - Esposito, Debora AU - Esposito D FAU - Rathinasabapathy, Thirumurugan AU - Rathinasabapathy T FAU - Poulev, Alexander AU - Poulev A FAU - Raskin, Ilya AU - Raskin I LA - eng GR - P50 AT002776/AT/NCCIH NIH HHS/United States GR - 2P50AT002776-06/AT/NCCIH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130217 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glycosides) RN - 0 (Melanocortins) RN - 0 (Plant Extracts) RN - 0 (Pregnanes) RN - 0 (pregnane glycoside) SB - IM MH - Animals MH - Appetite/drug effects MH - Asclepias/*chemistry MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cell Line, Tumor MH - Eating/*drug effects MH - Female MH - Glycosides/*administration & dosage MH - Humans MH - Male MH - Melanocortins/*metabolism MH - Models, Animal MH - Plant Extracts/*administration & dosage MH - Pregnanes/*administration & dosage MH - Rats MH - Rats, Wistar PMC - PMC3805381 MID - NIHMS516906 COIS- The authors declare no competing financial interest. EDAT- 2013/01/12 06:00 MHDA- 2013/12/16 06:00 PMCR- 2014/02/27 CRDT- 2013/01/12 06:00 PHST- 2013/01/12 06:00 [entrez] PHST- 2013/01/12 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2014/02/27 00:00 [pmc-release] AID - 10.1021/jf3033649 [doi] PST - ppublish SO - J Agric Food Chem. 2013 Feb 27;61(8):1841-9. doi: 10.1021/jf3033649. Epub 2013 Feb 17.