Medicinal history of North American Veratrum

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.

Keywords: Bezold–Jarisch reflex; Cancer; Hedgehog signaling pathway; Hypertension; Steroidal alkaloids.

Fig. 1

Geographic distribution of Veratrum species in North America. Emphasis is placed on species within Zomlefer et al.’s (2003) section Veratrum as these plants have been heavily investigated for the bioactive steroidal alkaloids they contain. Illustration adapted from distribution ranges in (Utech 2002) in Flora of North America, volume 26

Fig. 2

Steroidal alkaloids have been isolated from a wide range of plant and animal sources. Species of the genus Veratrum produce two broad classes of steroidal alkaloids: the Solanum alkaloids, which feature the classic cyclopentanophenanthrene ring structure and the Veratrum alkaloids, which feature a rearranged C-nor-D-homosteroidal ring structure in the C-ring is five membered and the D-ring is six membered

Fig. 3

Biosynthetic pathway for steroidal alkaloids in Veratrum plants as elucidated by Kaneko et al. in V. grandiflorum. a The nitrogen source for Veratrum alkaloids is likely l-arginine (Kaneko et al. 1976). b Based on the observation that solanidine accumulates in etiolated plants and is then rapidly turned into Veratrum alkaloids featuring a C-nor-D-homosteroidal skeleton upon illumination, Kaneko et al. (1972, 1979) hypothesized that this conversion is light and energy dependent. c Isolation of procevine suggests attack of the nitrogen atom on a suitable leaving group on C-18 precedes ring rearrangement in the formation of cevanine type alkaloids (Kaneko et al. 1978, 1979). d Cyclopamine was found to be an intermediate compound from which veratramine and jervine can be formed (Kaneko et al. 1970a, b)

Fig. 4

Cevanine alkamine bases. Esters of these bases reversibly bind to fast-sodium channels and lead to the Bezold–Jarisch reflex (hypotension, bradycardia, apnea) when injected into circulation

Fig. 5

Cyclopamine, cycloposine and jervine produce teratogenic effects in vertebrates by interfering with Hh signaling whereas the structurally similar and related alkaloids veratramine and tomatidine do not