Anti-Proliferative Activities of Terpenoids Isolated from Alisma orientalis and their Structure-Activity Relationships
Anti-Proliferative Activities of Terpenoids Isolated from Alisma orientalis and their Structure-Activity Relationships
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泽泻萜类化合物的抗增殖活性及其构效关系
DOI：
10.2174/1871520614666140601213514
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Lu, Jin-Jian
中科院分区：
文献类型：
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作者：
Xu, Wen;Li, Ting;Lu, Jin-Jian
本研究旨在从泽泻中分离萜类化合物。Juzep。并阐明了它们的抗增殖活性及构效关系。从东方木根茎中分离得到14个原烷型三萜。其中，茴香醇A(1)、茴香醇A 24-乙酸酯(2)、茴香醇B(3)、茴香醇B 23-乙酸酯(4)和茴香醇G(8)对癌细胞有抑制作用。化合物3和4的潜力最大；HepG2、MDA-MB-231和MCF-7细胞的IC50值分别为16.28、14.47和6.66 μ M(3)和18.01、15.97和13.56 μ M(4)。基于这些结果，我们得出结论，C-16的氧化程度和C-13和C-17之间的双键可能是抗增殖活性的重要因素。进一步研究表明，3和4能有效诱导细胞凋亡，流式细胞术证实了这一点。HepG2细胞经4处理后，细胞内钙浓度升高，内质网应激增加。虽然化合物1和2诱导的凋亡很小，但它们明显延缓了HepG2细胞的G2/M期。进一步研究表明，1-4也增强了LC3II的表达，表明发生了自噬。
This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 mu M for 3 and 18.01, 15.97, and 13.56 mu M for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.