title: Screening of medicinal plants for PPARα and PPARγ activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis.
abstract: Medicinal plants are a rich source of ligands for nuclear receptors. The present study was aimed to screen a collection of plant extracts for PPARα/γ-activating properties and identify the active extract that can stimulate cellular glucose uptake without enhancing the adipogenesis. A reporter gene assay was performed to screen ethanolic extracts of 263 plant species, belonging to 94 families, for activation of PPARα and PPARγ. Eight extracts showed activation of PPARγ, while 22 extracts showed activation of PPARα. The extracts of five plants (Daphne gnidium, Illicium anisatum, Juniperus virginiana, Terminalia chebula, and Thymelaea hirsuta) showed activation of both PPARα and PPARγ and out of them, D. gnidium and T. hirsuta markedly increased PPARα/γ protein expression. All five extracts showed an increase in cellular glucose uptake. Of the five dual agonists, T. chebula and T. hirsuta did not show any increase in differentiation of 3T3-L1 preadipocytes, but I. anisatum caused an increase in adipogenesis, while D. gnidium and J. virginiana were toxic to adipocytes. The adipogenic effect of rosiglitazone was antagonized by T. chebula and T. hirsuta. It was concluded that T. hirsuta and T. chebula retain the property of elevating glucose uptake as PPARα/γ dual agonists without the undesired side effect of adipogenesis. This is the first report to reveal the PPARα/γ dual agonistic action and glucose uptake enhancing property of T. hirsuta and T. chebula.
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, MS, USA.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Yang
authors.forename: Bharathi
authors.initials: B
authors.lastname: Avula
authors.forename: Troy
authors.initials: T
authors.lastname: Smillie
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D047493:PPAR alpha / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D047493:PPAR alpha; D047495:PPAR gamma; D010936:Plant Extracts; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005947:Glucose