| 摘要: | 異柴胡內酯源自南柴胡根部的萃取物之木酚素結構化合物，南柴胡在亞洲地區的國家常用於治療流感ヽ發燒ヽ瘧疾ヽ腫瘤ヽ女性經期不順等疾病。南柴胡根部萃取出的異柴胡內酯具有肺癌細胞毒殺性，然而在免疫調節相關的生物活性則少有文獻發表過。萃取出的異柴胡內酯包含近1:1的E 和 Z 構型的立體易構物。經由化學合成的方式分別取得E和Z的異柴胡內酯純異構物，經由實驗結果發現到Z構形的異柴胡內酯對小鼠巨噬細胞具有毒殺性，即Z構形是主要的抗癌活性的成份。然而沒有毒性的E構形異柴胡內酯用來測定抑制由活化巨噬細胞而誘導發炎的活性。實驗數據顯示E構形異柴胡內酯能夠抑制脂多醣刺激巨噬細胞產生的發炎因子，包括IL-6ヽTNF-??ヽIL-1??ヽNO與iNOS。在訊息傳遞途徑方面，E構形異柴胡內酯抑制了ERK1/2ヽp38以及JNK1/2之磷酸化。本實驗的數據表示E構形異柴胡內酯對細胞安全無毒性，且具有抗發炎活性，未來E構形異柴胡內酯可以在免疫調節的藥理研究上做更多的運用。
Isochaihulactone is a lignan isolated from Nan-Chai-Hu, the root of Bupleurum scorzonerifolium, an important Chinese herb in the treatment of influenza, fever, malaria, cancer, and menstrual disorders in China, Japan, and many other parts of Asia. Isochaihulactone has been reported to exhibit cytotoxicity against human lung cancers; however, its immune modulation properties have never been reported. Natural isolated isochaihulactone is composed E-form and Z-form isomers, and it is not clear which isomer responses for the bioactivities of isochaihulactone. Using organic synthesis, the pure E-form and Z-form isomers of isochaihulactone were obtained. We found that Z-form, but not E-form isochaihulactone is toxic to murine macrophages, indicating that Z-form isomer responses for the anti-cancer activity of isochaihulactone. Further, we found that E-form isochaihulactone reduced the expression of pro-inflammatory mediators, including TNF-α, IL-6, IL-1β, NO, and iNOS in LPS-stimulated macrophages. In addition, E-form isochaihulactone inhibited the phosphorylation of ERK1/2, p38, and JNK1/2 in LPS-stimulated macrophages. Our current results demonstrated the safety and anti-inflammatory properties of E-form isochaihulactone that could provide the possibility for its future pharmaceutical application in the realm of immune-modulation. |
