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Title: Screening of medicinal plants for PPPAR-alpha and PPAR-gamma activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis

Author
item YANG, MIN HYE - University Of Mississippi
item AVULA, BHARATHI - University Of Mississippi
item SMILLIE, TROY - University Of Mississippi
item KHAN, IKHLAS - University Of Mississippi
item KHAN, SHABANA - University Of Mississippi

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2013
Publication Date: 7/22/2013
Citation: Yang, M., Avula, B., Smillie, T., Khan, I.A., Khan, S.I. 2013. Screening of medicinal plants for PPPAR-alpha and PPAR-gamma activation and evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis. Planta Medica. 79:1084-1095.

Interpretive Summary: This manuscript describes the screening of 263 plant extracts for PPAR-aplha and PPAR-gamma activations and the antidiabetic properties of selected plant extracts. The extracts of five plants (Daphne gnidium, Illicium anisatum, Juniperus virginiana, Terminalia chebula and Thymelaea hirsuta) increased glucose uptake as a dual PPAR-alpha/gamma agonists and out of which, T. chebula and T. hirsuta didn’t induce adipogenesis. This is the first report to reveal the PPAR-alpha/gamma dual agonistic action and glucose uptake enhancing property of T. hirsuta and T. chebula. These plants may prove to be effective glucose-lowering agents in treatment of Type 2 diabetes mellitus.

Technical 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 PPAR-alpha/gamma 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 PPAR-alpha and PPAR-gamma. Eight extracts showed activation of PPAR gamma while 22 extracts showed activation of PPAR-alpha. The extracts of five plants (Daphne gnidium, Illicium anisatum, Juniperus virginiana, Terminalia chebula and Thymelaea hirsuta) showed activation of both PPAR-alpha and PPAR-gamma. All five extracts showed an increase in cellular glucose uptake. Of the five dualagonists, 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. Further studies indicated that T. chebula and T. hirsuta antagonized the adipogenic effect of rosiglitazone. It was concluded that T. hirsuta and T. chebula retain the property of elevating glucose uptake as PPAR-alpha/gamma dual agonists without the undesired side effect of adipogenesis. This is the first report to reveal the PPAR-alpha/gamma dual agonistic action and glucose uptake enhancing property of T. hirsuta and T. chebula.