桔梗根中三萜皂苷的抗增殖和凋亡活性及其构效关系,Planta Medica

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桔梗根中三萜皂苷的抗增殖和凋亡活性及其构效关系
Planta Medica ( IF 2.1 ) Pub Date : 2013-04-10 , DOI: 10.1055/s-0032-1328401
Jaemoo Chun ₁ , In Ha ₁ , Yeong Kim ₁

Affiliation

本研究旨在研究桔梗皂苷的抗增殖和凋亡活性，包括桔梗素 D、2''-O-乙酰桔梗素 D、3''-O-乙酰桔梗素 D、聚乳酸菌素 D、2''-O-乙酰聚乳酸菌素 D、和 3''-O-乙酰聚半乳糖 D，从桔梗中分离，以及缺乏 C-3 或 C-28 糖残基的前皂苷元，从桔梗 D 的水解中获得。我们还阐明了这些分子的构效关系以定义对桔梗皂苷和前皂苷元的生物活性至关重要的结构特征。结果表明，所有桔梗皂苷对所测试的七种癌细胞系均具有抗增殖作用。特别是，鼠李糖 C-2 或 C-3 位的 O-乙酰化和 C-24 的脱羟基增加了化合物的细胞毒性，而与 C-3 或 C-28 相连的糖残基的丢失则显着降低了细胞毒性。这种细胞毒性与细胞凋亡有关，这通过 DNA 片段化、磷脂酰丝氨酸外化和 AGS 细胞中半胱天冬酶的激活来表明。此外，桔梗皂苷抑制 Akt 的磷酸化，这导致 mTOR 和 NF-κB 信号传导在其下游蛋白受到抑制后受到抑制。总之，六种桔梗皂苷具有抗增殖活性，糖残基的存在、鼠李糖上的 O-乙酰基和 C-4 上的甲基有助于它们的细胞毒性和凋亡活性。

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Antiproliferative and Apoptotic Activities of Triterpenoid Saponins from the Roots of Platycodon grandiflorum and Their Structure-Activity Relationships

The present study was undertaken to investigate the antiproliferative and apoptotic activities of Platycodon saponins, including platycodin D, 2''-O-acetylplatycodin D, 3''-O-acetylplatycodin D, polygalacin D, 2''-O-acetylpolygalacin D, and 3''-O-acetylpolygalacin D, isolated from Platycodon grandiflorum, and prosapogenins which lack the C-3 or C-28 sugar residues, obtained from hydrolysis of platycodin D. We also clarified the structure-activity relationships of these molecules to define structural features that are crucial for the biological activity of Platycodon saponins and prosapogenins. The results showed that all Platycodon saponins had antiproliferative effects on the seven types of cancer cell lines tested. In particular, O-acetylation at the C-2 or C-3 position of rhamnose and dehydroxylation at C-24 increase the compound's cytotoxicity, while the loss of sugar residues linked to C-3 or C-28 dramatically reduced cytotoxicity. This cytotoxicity was associated with apoptosis, which was indicated by DNA fragmentation, phosphatidylserine externalization, and the activation of caspases in AGS cells. Furthermore, Platycodon saponins suppressed the phosphorylation of Akt, which resulted in the inhibition of mTOR and NF-κB signaling following the inhibition of their downstream proteins. In conclusion, six Platycodon saponins have antiproliferative activity, and the presence of sugar residues, an O-acetyl group on the rhamnose, and a methyl group at C-4 contributes to their cytotoxicity and apoptotic activity. These findings may be useful in evaluating the structure-activity relationships of Platycodon saponins and modifying them as a potent apoptosis-inducing agent.

更新日期：2013-04-10

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