a Department of Pharmacognosy, Faculty of Pharmacy , University of Szeged , Szeged , Hungary.
b Department of Medical Microbiology and Immunobiology, Faculty of Medicine , University of Szeged , Szeged , Hungary.
Pharm Biol. 2018 Dec;56(1):658-664. doi: 10.1080/13880209.2018.1548625.
Phytochemical and pharmacological data on Ducrosia anethifolia (DC.) Boiss. (Apiaceae), an Iranian medicinal plant, are scarce; however, furocoumarins are characteristic compounds of D. anethifolia.
Our experiments identify the secondary metabolites of D. anethifolia and assess their antitumor and anti-multidrug resistance activities.
Pure compounds were isolated from the extract of aerial parts of the plant by chromatographic methods. Bioactivities were tested on multidrug resistant and sensitive mouse T-lymphoma cell lines. The inhibition of the cancer MDR efflux pump ABCB1 was evaluated by flow cytometry (at 2 and 20 µM). A checkerboard microplate method was applied to study the interactions of furocoumarins and doxorubicin. Toxicity was studied using normal murine NIH/3T3 fibroblasts.
Thirteen pure compounds were isolated, nine furocoumarins namely, pabulenol (1), (+)-oxypeucedanin hydrate (2), oxypeucedanin (3), oxypeucedanin methanolate (4), (-)-oxypeucedanin hydrate (5), imperatorin (6), isogospherol (7), heraclenin (8), heraclenol (9), along with vanillic aldehyde (10), harmine (11), 3-hydroxy-α-ionone (12) and 2-C-methyl-erythrytol (13). Oxypeucedanin showed the highest in vitro antiproliferative and cytotoxic activity against parent (IC = 25.98 ± 1.27, 40.33 ± 0.63 µM) and multidrug resistant cells (IC = 28.89 ± 0.73, 66.68 ± 0.00 µM), respectively, and exhibited slight toxicity on normal murine fibroblasts (IC = 57.18 ± 3.91 µM).
Compounds 2, 3, 5, 7, 10-13 were identified for the first time from the Ducrosia genus. Here, we report a comprehensive in vitro assessment of the antitumor activities of D. anethifolia furocoumarins. Oxypeucedanin is a promising compound for further investigations for its anticancer effects.
关于伊朗药用植物 Ducrosia anethifolia（伞形科）的植物化学和药理学数据很少；然而，呋喃香豆素是 D. anethifolia 的特征化合物。
我们的实验旨在鉴定 D. anethifolia 的次生代谢产物，并评估其抗肿瘤和抗多药耐药活性。
采用色谱法从植物地上部分提取物中分离纯化合物。在多药耐药和敏感的小鼠 T 淋巴细胞系上测试生物活性。通过流式细胞术（在 2 和 20 µM 时）评估癌症 MDR 外排泵 ABCB1 的抑制作用。应用棋盘微量板法研究呋喃香豆素与阿霉素的相互作用。使用正常的小鼠 NIH/3T3 成纤维细胞研究毒性。
分离得到 13 种纯化合物，其中 9 种为呋喃香豆素，分别为：pabulenol（1）、（+）-氧化前胡素水合物（2）、氧化前胡素（3）、氧化前胡素甲醇（4）、（-）-氧化前胡素水合物（5）、异佛手柑内酯（6）、异缬草酸（7）、白头翁素（8）、白头翁醇（9），以及香草醛（10）、哈尔明（11）、3-羟基-α-紫罗兰酮（12）和 2-C-甲基-赤藓醇（13）。氧化前胡素对亲本（IC=25.98±1.27、40.33±0.63 µM）和多药耐药细胞（IC=28.89±0.73、66.68±0.00 µM）的体外增殖和细胞毒性活性最高，对正常小鼠成纤维细胞的毒性较小（IC=57.18±3.91 µM）。
化合物 2、3、5、7、10-13 首次从 Ducrosia 属中鉴定出来。在这里，我们报告了对 D. anethifolia 呋喃香豆素抗肿瘤活性的全面体外评估。氧化前胡素是一种很有前途的化合物，值得进一步研究其抗癌作用。
