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

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• 作者：Hsiang-Ru Lin ; ^{t3136@nknucc.nknu.edu.tw}
• 关键词：Tithonia diversifolia (Asteraceae) ; Peroxisome proliferator-activated receptor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：15 April, 2012
• 年：2012
• 卷：22
• 期：8
• 页码：2954-2958
• 全文大小：568 K

文摘

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) ¦Á and ¦Ã 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 PPAR¦Ã dependent promoters including PPRE (PPAR¦Ã response element), SHP, and ABCA1 gene promoters in dose-dependent manner. Furthermore, the fluorescence polarization competitive binding assay showed that tirotundin (IC₅₀ = 27 ¦ÌM) and tagitinin A (IC₅₀ = 55 ¦ÌM) enhanced PPAR¦Ã transactivation activity by directly binding to PPAR¦Ã ligand binding domain. Additionally, they stimulated the transactivation of PPAR¦Á dependent SULT2A1 gene promoter by 2.3-fold of vehicle effect at 10 ¦ÌM. These results highly indicated that tirotundin and tagitinin A are the active components of T. diversifolia to exert anti-diabetic effect through PPAR¦Ã pathway. Moreover, these sesquiterpene lactones behaved as PPAR¦Á/¦Ã dual agonists so they might be useful as the potential herbal treatment for diabetes.