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Medicinal history of North American Veratrum

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Abstract

Plants belonging to the genus Veratrum have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in Veratrum species, some of which are potent bioactives. This review discusses Veratrum species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus Veratrum (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the Veratrum plants of North America and the medicinal uses of their bioactive steroidal alkaloids.

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Notes

  1. Near the same time, researchers Saito et al. in Japan isolated the Veratrum alklaoids jervine and veratramine from V. grandiflorum, a member of the V. album complex (Saito and Suginome 1936; Saito 1940). Though not hypotensive Veratrum alkaloids, these compounds would be the subject of greater medical investigation in the 1960s and 1970s. See the section on teratogenic Veratrum alkaloids.

  2. Seiferle et al. (1942) produced the first modern isolation of jervine, pseudojervine, rubijervine, protoveratridine, and germine from V. viride.

  3. Notably, Kupchan et al. also isolated the alkamine germine from Zigadenus venenosus, further cementing the phytochemical relationship between the species of Veratrum and Zigadenus (Kupchan and Deliwala 1953).

  4. The numerous permutations of cevanine ester-alkaloids with hypotensive qualities are substantial and the reader is directed to see the outstanding reviews by Kupchan (1961) and Krayer and Meilman (1977) for a more complete discussion of the phytochemistry and medical applications of these compounds respectively.

Abbreviations

USDA:

United States Department of Agriculture

NRCS:

National Resources Conservation Service, formerly the US Soil Conservation Service

IUPAC:

International Union of Pure and Applied Chemistry

HPE:

Holoprosencephalopathy, a developmental abnormality in which the prosencephalon of the embryo fails to divide into separate hemispheres causing defects in facial and brain structures

Hh:

Hedgehog, used in reference to the complete series of biochemical events and structures that make up the embryonic hedgehog signaling pathway

hh :

Invertebrate hedgehog gene, originally discovered in Drosophila

shh :

Vertebrate Sonic hedgehog gene

ihh :

Vertebrate Indian hedgehog gene

dhh :

Vertebrate Desert hedgehog gene

Shh:

Sonic hedgehog protein, potent morphogen coded for by shh

Shh-Np :

Active Sonic hedgehog protein, 19 kDa N-terminal fragment produced by autolytic cleavage of Shh and subsequent palmitoylation of the N-terminus and addition of cholesterol to the C-terminus

Ptch:

Patched, a twelve pass transmembrane transport protein integral to the hedgehog signaling pathway which serves as the binding site for the active Sonic hedgehog protein and regulates the activity of Smoothened

Smo:

Smoothened, a seven transmembrane G-protein like receptor integral to the hedgehog signaling pathway; initiates the signaling cascade regulating the activity of Gli transcription factors

NBCCS:

Nevoid basal cell carcinoma syndrome, an autosomal-dominant inherited condition characterized by craniofacial malformations, spina bifida, and polydactylism in addition to high rates of basal cell carcinoma and cancers of the heart, ovaries, skin, and central nervous system

BCC:

Basal cell carcinoma, most common non-melanoma skin cancer; characterized by uncontrolled growth of cells in the stratum basale, the skin’s lowest layer

PNET:

Primitive neuroectodermal tumor, tumors originating in cells derived from the neuroectoderm such as medulloblastomas

KAAD-cyclopamine:

3-Keto N-aminoethyl aminocaproyl dihydrocin-namoyl cyclopamine, a potent hedgehog pathway antagonist derived from the natural product cyclopamine

CSC:

Cancer stem cell, highly proliferative undifferentiated tumor cells, which give rise to rapidly dividing “bulk” tumor cells

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Acknowledgments

We would like to thank the Office of Sponsored Projects at Boise State University, Boise, ID and Mountain States Tumor Medical Research Institute for their support of this project. The project described was also supported by the INBRE Program, NIH Grant Nos. P20 RR016454 (National Center for Research Resources) and P20 GM103408 (National Institute of General Medical Sciences).

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  1. Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID, 83725-1520, USA

    Christopher M. Chandler & Owen M. McDougal

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Correspondence to Owen M. McDougal.

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Chandler, C.M., McDougal, O.M. Medicinal history of North American Veratrum . Phytochem Rev 13, 671–694 (2014). https://doi.org/10.1007/s11101-013-9328-y

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