title: Molecular decodification of gymnemic acids from Gymnema sylvestre. Discovery of a new class of liver X receptor antagonists.
abstract: The individual chemical components of commercial extract of Gymnema sylvestre, a medicinal plant used in the traditional systems of the Indian medicine for its antidiabetic and hypolipidemic properties, were isolated and evaluated for their capability to act as modulators of nuclear and membrane receptors involved in glucose and lipid homeostasis. The study disclosed for the first time that individual gymnemic acids are potent and selective antagonists for the β isoform of LXR. Indeed the above activity was shared by the most abundant aglycone gymnemagenin (10) whereas gymnestrogenin (11) was endowed with a dual LXRα/β antagonistic profile. Deep pharmacological investigation demonstrated that gymnestrogenin, reducing the expression of SREBP1c and ABCA1 in vitro, is able to decrease lipid accumulation in HepG2 cells. The results of this study substantiate the use of G. sylvestre extract in LXR mediated dislypidemic diseases.
authors: Department of Surgery and Biomedical Sciences, Nuova Facoltà di Medicina, P.zza L. Severi, 1-06132 Perugia, Italy.
authors: Barbara
authors: B
authors: Renga
authors: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, I-80131 Naples, Italy.
authors: Carmen
authors: C
authors: Festa
authors: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, I-80131 Naples, Italy.
authors: Simona
authors: S
authors: De Marino
authors: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy.
authors: Simone
authors: S
authors: Di Micco
authors: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, I-80131 Naples, Italy.
authors: Maria Valeria
authors: MV
authors: D'Auria
authors: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy.
authors: Giuseppe
authors: G
authors: Bifulco
authors: Department of Surgery and Biomedical Sciences, Nuova Facoltà di Medicina, P.zza L. Severi, 1-06132 Perugia, Italy.
authors: Stefano
authors: S
authors: Fiorucci
authors: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, I-80131 Naples, Italy. Electronic address: angela.zampella@unina.it.
authors: Angela
authors: A
authors: Zampella
mesh_terms: D055808:Drug Discovery; D031104:Gymnema sylvestre / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D000071518:Liver X Receptors; D008958:Models, Molecular; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012503:Saponins; D014315:Triterpenes; C007898:gymnemic acid
keywords: Gymnema sylvestre; Gymnemic acids; Liver-X-receptor; Steroid nuclear receptors