Honokiol: a non-adipogenic PPARγ agonist from nature.

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2013
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Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators.We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists.The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain.We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo.This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.
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atanasov2013honokiolbiochimica Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Atanasov, Atanas G;Wang, Jian N;Gu, Shi P;Bu, Jing;Kramer, Matthias P;Baumgartner, Lisa;Fakhrudin, Nanang;Ladurner, Angela;Malainer, Clemens;Vuorinen, Anna;Noha, Stefan M;Schwaiger, Stefan;Rollinger, Judith M;Schuster, Daniela;Stuppner, Hermann;Dirsch, Verena M;Heiss, Elke H;
Journal biochimica et biophysica acta
Year 2013
DOI
10.1016/j.bbagen.2013.06.021
URL
Keywords
NMR HPLC sodium carboxymethyl cellulose SEM metabolic disease high-performance liquid chromatography gst ampk nox mtor traditional chinese medicine thin layer chromatography glutathione-s-transferase nf-κb mammalian target of rapamycin nuclear magnetic resonance dimethyl sulfoxide fcs pbs fetal calf serum peroxisome proliferator-activated receptor gamma tlc bovine serum albumin dmso bmp natural product bsa anova srebp pparγ dmem phosphate buffered saline lbd 3-isobutyl-1-methylxanthine amp-activated kinase atcc american type culture collection badge cmcna dulbecco's modified eagle's medium ec(50) egfp ibmx mef nadph-dependent oxidase nbs peroxisome proliferator-activated receptor rxr spf tcm tr-fret analysis of variance bisphenol a diglycidyl ether bone morphogenic protein 4 effective concentration 50% enhanced green fluorescent protein ligand-binding domain mouse embryonic fibroblasts newborn bovine serum nuclear factor κb retinoic x receptor specific pathogen free standard error of the mean sterol regulatory element binding protein time-resolved fluorescence resonance energy transfer

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