Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan.
Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, 859-3298, Japan.
J Nat Med. 2024 Jan;78(1):226-235. doi: 10.1007/s11418-023-01744-4. Epub 2023 Sep 1.
From the methanolic extract of the climbing stems and rhizomes of Sinomenium acutum, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/β-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/β-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/β-catenin pathway.
从青风藤爬藤茎和根茎的甲醇提取物中，分离得到了两种新的阿朴啡类似物，即青藤碱 I 和 II，以及包括千里光碱在内的 15 种已知化合物。根据 NMR 和 MS 光谱等化学/物理化学证据，解析了分离得到的新化合物的化学结构。对于青藤碱 I 和 II，通过比较实验和预测的电子圆二色性 (ECD) 数据确定了它们的绝对构型。我们比较了分离得到的化合物与报道的天然 Wnt/β-catenin 通路抑制剂荷叶碱的抗增殖活性。在所分离的化合物中，我们发现千里光碱对人结肠癌细胞系 HT-29 及其癌症干细胞 (CSC) 均具有抗增殖活性。千里光碱对非 CSCs 和其 CSCs 的 IC 值均低于荷叶碱。此外，Western blot 分析结果表明，千里光碱抑制了 Wnt/β-catenin 通路靶蛋白如生存素的表达。这些结果表明，千里光碱通过抑制 Wnt/β-catenin 通路发挥细胞毒性作用。
