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Molecules 2018, 23(9), 2222; https://doi.org/10.3390/molecules23092222

Native V. californicum Alkaloid Combinations Induce Differential Inhibition of Sonic Hedgehog Signaling

1
Biomolecular Sciences Graduate Programs, Boise State University, 1910 University Drive, Boise, ID 83725, USA
2
Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID 83725, USA
*
Author to whom correspondence should be addressed.
Received: 28 July 2018 / Revised: 22 August 2018 / Accepted: 30 August 2018 / Published: 1 September 2018
(This article belongs to the Special Issue Advances in Plant Alkaloid Research)
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Abstract

Veratrum californicum is a rich source of steroidal alkaloids such as cyclopamine, a known inhibitor of the Hedgehog (Hh) signaling pathway. Here we provide a detailed analysis of the alkaloid composition of V. californicum by plant part through quantitative analysis of cyclopamine, veratramine, muldamine and isorubijervine in the leaf, stem and root/rhizome of the plant. To determine whether additional alkaloids in the extracts contribute to Hh signaling inhibition, the concentrations of these four alkaloids present in extracts were replicated using commercially available standards, followed by comparison of extracts to alkaloid standard mixtures for inhibition of Hh signaling using Shh-Light II cells. Alkaloid combinations enhanced Hh signaling pathway antagonism compared to cyclopamine alone, and significant differences were observed in the Hh pathway inhibition between the stem and root/rhizome extracts and their corresponding alkaloid standard mixtures, indicating that additional alkaloids present in these extracts are capable of inhibiting Hh signaling. View Full-Text
Keywords: hedgehog signaling; Veratrum californicum; cyclopamine; HPLC-MS; Shh-Light II cells hedgehog signaling; Veratrum californicum; cyclopamine; HPLC-MS; Shh-Light II cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Turner, M.W.; Cruz, R.; Elwell, J.; French, J.; Mattos, J.; McDougal, O.M. Native V. californicum Alkaloid Combinations Induce Differential Inhibition of Sonic Hedgehog Signaling. Molecules 2018, 23, 2222.

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