title: Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.
abstract: Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements.
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Waltenberger
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Pferschy-Wenzig
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Blunder
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Malainer
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Tina
authors.initials: T
authors.lastname: Blazevic
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Elke H
authors.initials: EH
authors.lastname: Heiss
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kopp
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria.
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.affiliation: Department of Pharmacognosy, University of Vienna, Austria. Electronic address: atanas.atanasov@univie.ac.at.
authors.forename: Atanas G
authors.initials: AG
authors.lastname: Atanasov
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D001688:Biological Products; D047495:PPAR gamma
keywords: (−)-Catechin (PubChem CID: 73160); Amorfrutin 1 (PubChem CID: 10132170); Diabetes; Falcarindiol (PubChem CID: 5281148); Honokiol (PubChem CID: 72303); Linolenic acid (PubChem CID: 5280934); Magnolol (PubChem CID: 72300); Natural product; Nuclear receptor; Nutrition; PPAR gamma; Pioglitazone (PubChem CID: 4829); Quercetin (PubChem CID: 5280343); Resveratrol (PubChem CID: 445154); Rosiglitazone (PubChem CID: 77999)
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