P-36 甘茶成分thunberginol類の合成と抗アレルギー活性 : 構造活性相関および作用様式(ポスター発表の部)

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Inhibitory effects of phyllodulcin (1), hydrangenol (2), thunberginols 3-8 from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangea Dulcis Folium) on the release of β-hexosaminidase and production of cytokines in rat basophilic leukemia (RBL-2H3) cells were examined. As a result, thunberginols A (3), B (4), and F (7) substantially inhibited the degranulation by antigen and calcium ionophore A23187, and the releases of TNF-α and IL-4 by antigen in RBL-2H3 cells. Phyllodulcin (1) and hydrangenol (2) also showed weak inhibition for the degranulation. With regard to structural requirement thunberginols for the activity, the 3,4-double bond and oxygen function on the aromatic rings were essential for the strong activity and the lactone ring enhanced the activity. Thunberginols B (4), which was found to show potent activity, was minor component. To evaluate the anti-allergic activity in vivo and clarify the action mechanism of 4, synthesize of 4 in large scale was needed. Therefore, we developed efficient constructive method of isocoumarin skeleton and applied the total synthesis of 4. Thunberginols B (4) significantly exhibited the antiallergic activity at a dose of 100mg/kg, p.o., whose activity was equivalent for that of a reference compound, tranilast. Next, the action mechanisms of thunberginols were investigated. Thunberginols A (3), B (4), and F (7) inhibited increase in intracellular Ca^<2+> level in RBL-2H3 cells induced by antigen. Thunberginol B (4) was found to inhibit mRNA expression of c-fos, phosphorylation of ERK, and phosphorylation of c-Jun in the nucleus. In addition, thunberiginol B (4) showed concentration-dependent inhibitory activity on the mRNA expression of IL-2, 3, 4, 13, TNF-α, and GM-CSF induced by antigen.
天然有機化合物討論会の論文
2007-08-24

P-36 甘茶成分thunberginol類の合成と抗アレルギー活性 : 構造活性相関および作用様式(ポスター発表の部)

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