Anti-obesity effect of phenylcoumarins from two Calophyllum spp in 3T3-L1 adipocytes

Résumé

Purpose: To evaluate the anti-obesity effects of five compounds isolated from Calophyllum andersonnii and Calophyllum sclerophyllum, viz, friedelin (CP1), friedelinol (CP2), isodispar B (CP3), 5,7-dihydroxy-6-(3-methybutyryl)-4-phenylcoumarin (CP4) and 5,7-dihydroxy-6-(2-methybutyryl)-4-phenylcoumarin (CP5) in 3T3-L1 mouse pre-adipocytes.Methods: Maximum non-toxic doses (MNTDs) of CP1 - CP5 were obtained by conducting 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Intracellular lipid droplet accumulation was determined by Oil Red O (ORO) staining. The effects of CP1 - 5 on the expression of adipogenesis transcriptional factors, namely, C/ebpα, Pparγ1, aP2 and on cellular glucose uptake and adipokine (adiponectin, leptin, resistin) secretion were assessed by commercial colorimetric and ELISA kits, respectively.Results: MNTDs for CP1-CP5 were 3.0, 1.4, 1.0, 29.0 and 25.0 μM, respectively. 3T3-L1 cells treated with CP1 - CP3 showed increased lipid accumulation (p < 0.05) and decreased glucose uptake (p < 0.05), compared with untreated cells; cells treated with CP4 and CP5 had opposite effects. Cells treated with CP4 and CP5 also showed downregulated Pparγ1, C/ebpα and aP2 expression (p < 0.05), compared with untreated cells. The anti-adipogenic property exerted by CP4 and CP5 manifested as increased secretion of adiponectin as well as reduced leptin and resistin levels.Conclusion: CP4 and CP5 isolated from Calophyllum sclerophyllum show promising anti-obesity properties, and could serve as candidate hits for further investigation at in vivo level to provide additional mechanistic evidence.Keywords: Phenylcoumarin, Calophyllum, Adipogenesis, Adipocyte, Adipokine, Obesity

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