吳茱萸次鹼代謝物之合成與抗發炎活性評估

Synthesis and Anti-inflammatory Effect of Four Rutaecarpine Metabolites

吳茱萸次鹼是中藥吳茱萸中主要的成份，其結構屬於quinazolinocarboline，在先前的研究我們發現吳茱萸次鹼被肝微粒體酵素代謝成四個代謝產物，分別為3- 羥基吳茱萸次鹼、10-羥基吳茱萸次鹼、11- 羥基吳茱萸次鹼及12- 羥基吳茱萸次鹼，本研究以簡易的合成方式合成出這四個吳茱萸次鹼的代謝產物，並探討這些化合物對脂多醣誘導之RAW264.7 巨噬細胞生成一氧化氮之抑制效果，結果顯示3- 羥基吳茱萸次鹼具有最好的抗發炎活性，其EC50 值為27.1 μM。Rutaecarpine is a main quinazolinocarboline alkaloid isolated from Evodia rutaecarpa . In our previous studies, rutaecarpine was metabolized by liver microsomal enzymes to yield four rutaecarpine metabolites, 3-, 10-, 11-, and 12-hydroxyrutaecarpine. In this report, we described the detailed synthesis of these four metabolites and evaluated their anti-inflammatory effect on lipopolysaccheride-induced NO production in RAW264.7 macrophages. Among them, 3-hyroxyrutaecarpine showed the most potent anti-inflammatory activity with EC50 value 27.1 μM.