Publication Date

8-2022

Date of Final Oral Examination (Defense)

5-11-2022

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Chemistry

Department

Chemistry

Major Advisor

Owen McDougal, Ph.D.

Advisor

Lisa Warner, Ph.D.

Advisor

Julia Oxford, Ph.D.

Abstract

Plants of the Veratrum genus have been used throughout history for their emetic properties, rheumatism, and for the treatment of high blood pressure. However, inadvertent consumption of these plants, which resemble wild ramps, induces life threatening side effects attributable to an abundance of steroidal alkaloids. Several of the steroidal alkaloids from Veratrum spp. have been investigated for their ability to antagonize the Hedgehog (Hh) signaling pathway, a key pathway for embryonic development and cell proliferation. Uncontrolled activation of this pathway is linked to the development of various cancers, most notably basal cell carcinoma and acute myeloid leukemia. Additional investigation of Veratrum spp. may lead to the identification of novel alkaloids with potential to serve as chemotherapeutics. This project aimed to identify steroidal alkaloids in V. parviflorum, perform a toxicological investigation for the presence of these alkaloids in the blood and breast milk of patients who ingested V. parviflorum, and evaluate the bioactivity of these alkaloids for inhibiting the Hh signaling pathway. Four steroidal alkaloids were identified in the ethanolic extract of V. parviflorum: cyclopamine, veratramine, jervine, and muldamine. Cyclopamine, veratramine, and jervine were identified in patient blood while cyclopamine and veratramine were identified in patient breast milk. A bioactivity assessment of the V. parviflorum extract using Shh-Light cells suggested that there are additional compounds within the plant that are antagonistic to the Hh signaling pathway.

DOI

https://doi.org/10.18122/td.1996.boisestate

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