Sesquiterpene lactones from Tithonia diversifolia act as peroxisome proliferator-activated receptor agonists.

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Lin HR

Sesquiterpene lactones from Tithonia diversifolia act as peroxisome proliferator-activated receptor agonists.

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2954-8. doi: 10.1016/j.bmcl.2012.02.043. Epub 2012 Mar 3.

PubMed ID
22424975 [ View in PubMed
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Abstract

Tithonia diversifolia is a well-known traditional Chinese medicine treating diabetes, hepatitis, and hepatocarcinoma but its molecular mechanism is not fully understood. Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are members of nuclear receptor superfamily. Their agonists are prescribed as antihyperlipidemic and antihyperglycemic drugs now. In this study, sesquiterpene lactones, tirotundin and tagitinin A, were isolated from T. diversifolia and evaluated for their activity against PPARs by the transient transfection reporter assay. Tirotundin and tagitinin A transactivated PPARgamma dependent promoters including PPRE (PPARgamma response element), SHP, and ABCA1 gene promoters in dose-dependent manner. Furthermore, the fluorescence polarization competitive binding assay showed that tirotundin (IC(50)=27 muM) and tagitinin A (IC(50)=55 muM) enhanced PPARgamma transactivation activity by directly binding to PPARgamma ligand binding domain. Additionally, they stimulated the transactivation of PPARalpha dependent SULT2A1 gene promoter by 2.3-fold of vehicle effect at 10 muM. These results highly indicated that tirotundin and tagitinin A are the active components of T. diversifolia to exert anti-diabetic effect through PPARgamma pathway. Moreover, these sesquiterpene lactones behaved as PPARalpha/gamma dual agonists so they might be useful as the potential herbal treatment for diabetes.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
PioglitazonePeroxisome proliferator-activated receptor gammaIC 50 (nM)8000N/AN/ADetails
TroglitazonePeroxisome proliferator-activated receptor gammaIC 50 (nM)2600N/AN/ADetails