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从加州藜芦中通过提取方法获得的环杷明生物活性。

Cyclopamine bioactivity by extraction method from Veratrum californicum.

作者信息

Turner Matthew W, Cruz Roberto, Mattos Jared, Baughman Nic, Elwell Jordan, Fothergill Jenny, Nielsen Anna, Brookhouse Jessica, Bartlett Ashton, Malek Petr, Pu Xinzhu, King Matthew D, McDougal Owen M

机构信息

Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID 83725, United States; Biomolecular Sciences Ph.D. Program, Boise State University, 1910 University Drive, Boise, ID 83725, United States.

Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID 83725, United States.

出版信息

Bioorg Med Chem. 2016 Aug 15;24(16):3752-7. doi: 10.1016/j.bmc.2016.06.017. Epub 2016 Jun 14.

Abstract

Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine, a potent inhibitor of the Hedgehog (Hh) signaling pathway. The Hh pathway is a crucial regulator of many fundamental processes during vertebrate embryonic development. However, constitutive activation of the Hh pathway contributes to the progression of various cancers. In the present study, a direct correlation was made between the extraction efficiency for cyclopamine from root and rhizome by eight methods, and the associated biological activity in Shh-Light II cells using the Dual-Glo® Luciferase Assay System. Alkaloid recovery ranged from 0.39 to 8.03mg/g, with ethanol soak being determined to be the superior method for obtaining biologically active cyclopamine. Acidic ethanol and supercritical extractions yielded degraded or contaminated cyclopamine with lower antagonistic activity towards Hh signaling.

摘要

加州藜芦,通常被称为玉米百合或加州假藜芦,生长在高山草甸中,并产生甾体生物碱环杷明,一种有效的刺猬(Hh)信号通路抑制剂。Hh通路是脊椎动物胚胎发育过程中许多基本过程的关键调节因子。然而,Hh通路的组成性激活促进了各种癌症的进展。在本研究中,使用Dual-Glo®荧光素酶检测系统,对八种方法从根和根茎中提取环杷明的效率与Shh-Light II细胞中的相关生物活性进行了直接关联。生物碱回收率在0.39至8.03mg/g之间,乙醇浸泡被确定为获得具有生物活性的环杷明的最佳方法。酸性乙醇和超临界萃取产生的环杷明降解或受污染,对Hh信号的拮抗活性较低。

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