A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13β-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 μM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 μM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.

中文翻译：

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枫香三萜类化合物通过 PI3K-AKT 相关信号通路诱导 SMMC7721 癌细胞凋亡

从 Liquidambar formosana (Hamamelidaceae) 中分离出一种先前未描述的蒲公英型三萜，它是一类罕见的天然蒲公英三萜，具有 14、28-内酯、两种未描述的齐墩果型三萜和 25 种已知三萜的骨架。未描述的化合物的结构是在 1D 和 2D NMR 光谱、HR-ESI-MS 和 X 射线晶体学数据分析的基础上确定的。在分离物中，熊果酸、3,6-dion-20(29)-lupen-28-oic acid 和 3-oxo-12α-hydroxyoleanan-28,13β-olide 在流式细胞仪中诱导 SMMC7721 细胞显着凋亡在 8.0 μM 下分别以 94.5%、57.3% 和 89.9% 的凋亡率进行实验，表现出与该阳性药物紫杉醇几乎相等的凋亡诱导能力（在 1.4 μM 时凋亡率为 71.2%）。机制研究表明，这三种化合物可以通过上调促凋亡因子（Bad和Bax）的表达，激活caspase-3和caspase-9诱导细胞凋亡来调节线粒体途径。进一步的研究表明，这三种化合物的促凋亡作用与 PI3K-AKT 通路抑制有关。综上所述，这些研究提供的证据表明，来自枸杞的三萜是肝细胞癌治疗的有希望的候选者。