吳茱萸水抽提物及其純化成份與L型鈣離子通道上dihydropyridine結合處相互作用之評估

Evaluation of the Water Extract and Some Pure Principles of Evodiae Fructus on 1,4-Dihydropyridine Binding Site of L-Type Calcium Channels

本研究使用放射性藥物結合評估法，探討吳茱萸(Evodiae Fructus)水抽提物及其純化成份如去氫吳茱萸鹼(dehydroevodiamine)、吳茱萸鹼(evodiamine)、吳茱萸次鹼(rutaecarpine)、rhetsinine、limonin, isorhamnetin-o-galactoside、quercetin-3-o-galactoside及synephrine是否與L-型鈣離子通道上的dihydropyridine (DHP)結合處有相互作用。實驗結果顯示吳茱萸(5~100mg/ml)有意義地競爭[3H] nimodipine結合至ICR小鼠大腦皮質及心臟細胞膜上的DHP結合處，其抑制常數(Ki)分別為17.3及7.9mg/ml。然而，於本研究測試之所有吳茱萸純化成份（除去氫吳茱萸鹼外）於濃度達到100μM時仍未見其與DHP結合處有明顯相互作用。去氫吳茱萸鹼作用在心臟細胞膜上DHP結合處之Ki值為403μM。如把吳茱萸水抽提物中去氫吳茱萸鹼含量代入計算，則去氫吳茱萸鹼作用在DHP結合處之強度約差吳茱萸水抽提物一百倍。因此，上述結果顯示吳茱萸含有會作用到L型鈣離子通道上DHP結合處之成份，但此成份不是上列所述之任何純化合物。

The interactions of the water extract of Evodiae Fructus (EF, the unripe fruit of Evodia rutaecarpa) and its pure principles, such as dehydroevodiamine (DeHE), evodiamine, rutaecarpine, rhetsinine, limonin, isorhamnetin-3-o-galactosidc, quercetin-3-o-galactoside, and synephrine, with the dihydropyridine (DHP) binding site of L-type calcium channels were studied by radioligand binding assay. The results showed that HF (5-100 mg/mi) significantly competed with [3H] nimodipine for specific binding to DHP binding sites in the ICR mice cortex and heart membrane preparations with a K value of 17.3 and 7.9 mg/ml, respectively. However, all pure principles of EF (except DeHE) tested in the present study had no significant interactions with DHP binding sites even at the concentration of 100 μM in both membrane preparations. The K(subscript i) value of DeHE for DHP binding sites in the heart membrane preparations was 403 μM, which was 100-fold less potent than EF when the content of DeHE in EF was taken into account. Therefore, HF must contain the principles other than the pure compounds tested, which act on the DHP binding site of L-type calcium channels.