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通过代谢组学和网络药理学分析揭示红芸豆种皮抗 B16-F10 黑素瘤细胞的增殖机制和生物活性化合物。

Uncovering the anti-proliferation mechanism and bioactive compounds in red kidney bean coat against B16-F10 melanoma cells by metabolomics and network pharmacology analysis.

机构信息

Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China.

出版信息

Food Funct. 2019 Feb 20;10(2):912-924. doi: 10.1039/c8fo01738g.

DOI:10.1039/c8fo01738g
PMID:30698192
Abstract

In this study, coat (RKBC) and kernel (RKBK) extracts of red kidney bean were prepared, and their chemical compositions and potential anti-cancer activity against B16-F10 cells were evaluated. Then the anti-proliferation mechanisms of the active RKBC extract were investigated by flow cytometry analysis, cellular metabolomics, network pharmacology and western blotting. The RKBC extract inhibited B16-F10 cell proliferation and migration in a dose-dependent manner. Further analysis showed that RKBC induced G1 and G2/M phase arrest, and triggered apoptosis and vacuolization. Mechanistically, RKBC significantly increased the cellular content of cGMP, decreased the levels of AKT1/2/3 and cleaved-MMP2, and up-regulated the expression of Bcl-xl. Besides, network pharmacology revealed that RKBC potentially influenced the cell cycle via the regulation of CDK2 and CDK4. Finally, quercetin might serve as the major active component in the RKBC extract. In conclusion, our study showed the potential of the RKBC extract for the prevention or treatment of melanoma.

摘要

在这项研究中,制备了红芸豆的外壳(RKBC)和内核(RKBK)提取物,并评估了它们的化学成分和对 B16-F10 细胞的潜在抗癌活性。然后,通过流式细胞术分析、细胞代谢组学、网络药理学和 Western blot 研究了活性 RKBC 提取物的抗增殖机制。RKBC 提取物呈剂量依赖性抑制 B16-F10 细胞增殖和迁移。进一步的分析表明,RKBC 诱导 G1 和 G2/M 期阻滞,并引发细胞凋亡和空泡化。在机制上,RKBC 显著增加了细胞内 cGMP 的含量,降低了 AKT1/2/3 和 cleaved-MMP2 的水平,并上调了 Bcl-xl 的表达。此外,网络药理学表明 RKBC 可能通过调节 CDK2 和 CDK4 来影响细胞周期。最后,槲皮素可能是 RKBC 提取物中的主要活性成分。总之,本研究表明 RKBC 提取物具有预防或治疗黑色素瘤的潜力。

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