Journal
MOLECULES
Volume 23, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/molecules23092222
Keywords
hedgehog signaling; Veratrum californicum; cyclopamine; HPLC-MS; Shh-Light II cells
Funding
- Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103408, P20GM109095]
- National Science Foundation [0619793, 0923535]
- MJ Murdock Charitable Trust
- Idaho State Board of Education, and Research Corporation
- Direct For Biological Sciences
- Div Of Biological Infrastructure [0619793] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0923535] Funding Source: National Science Foundation
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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.
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