Veratrum californicum var. californicum
Trinity Alps Wilderness, CA, July 1973. Growing abundantly along edge of Granite Lake, cattle observed grazing
in the area
 

Veratrum californicum
var. californicum

Morris Meadows
Stewart Fork Trail,
Trinity Alps Wilderness,
Trinity Co., CA, July 1969

Veratrum californicum
Russian Wilderness,
Taylor Lake,
~6,500 ft elev., CA, July 2005.

Veratrum californicum
var. californicum

Haypress Meadows
Marble Mts. Wilderness,
Siskiyou Co., CA, July 2004

Veratrum californicum
Marble Mountains Wilderness,
Meadow below Boulder Peak,
CA, ~7,000 ft elev., July 2005.

Veratrum californicum var. californicum

Veratrum californicum var. californicum

Veratrum californicum var. californicum

Boise National Forest, ID
Corn lilies growing singly in wooded understory of pine woodland, instead of in wet meadows, 4,000 ft.  SPJ-15963
August 2005

Veratrum californicum var. californicum

Payette National Forest, ID
Corn lilies growing singly in wooded understory of pine woodland, instead of in wet meadows, 4,000 ft.  SPJ-15964
August 2005

Veratrum californicum var. californicum

Veratrum californicum var. californicum

Veratrum californicum var. californicum
Sawtooth National Forest, Idaho,
wet ravine ~ 7,200 ft elev.
June 2005

Veratrum californicum var. californicum
 

Veratrum californicum var. caudatum
Vicinity of Oregon State University campus, Nov. 2004.  Localized patch of ~200 plants in
swampy meadow.  Close-up of infructescence showing septicidal capsules, some still containing seeds.

Veratrum insolitum
Klamath National Forest, CA,
Elev. ~4,000 ft, July 2005

Veratrum insolitum
near Bald Hills, CA,
July 2005

Veratrum viride
Kenai Peninsula, AK
Spjut & Marin 15396, July 2003

Veratrum viride
Kenai Peninsula, AK
Spjut & Marin 15396, July 2003

Selected References:

Anonymous.  1967. Veratrum alkaloids in the therapy of myasthenia gravis.  Can. Med. Assoc. J. 96(23): 1534–1535.

Bastin, 1895.  E. S. Structure of Veratrum viride.  Amer. J. Pharm. 67 (4): 1–8. Botanical Medicine Monographs and Sundry.  The Southwest School of Botanical Medicine http://www.swsbm.com.  This is about the morphological structure of the root-rhizome.

Binns W., L. F. James, R. F. Keeler and L. D. Balls.  1968.  Effects of teratogenic agents in range plants.  Cancer Res. 28(11): 2323–3236.

Cholakova M., V. Christov, N. Kostova, R. Todorova, E. Georgieva and E. Nikolova.  2005.  Biological activity of Veratrum alkaloids.  Exp. Pathol. Parasitol. 8(2): 16–19.  “The biological activity and the chemical classification of alkaloids isolated from Veratrum plants are discussed.”  The article mentions that cyclopamine has been isolated from several species.

Contois, M., J. Cahill, N. Chavez, C. Cacace, G.I.  Wechsler, M. Pauli and E. Kosman.  2004.  Estimating Corn Lily Abundance in Bear Trap Meadow, July 2004. http://userwww.sfsu.edu/~efc/classes/biol315/cornlily.pdf

Cosgriff, R., V. J. Anderson, and S. Monson. 2004.  Restoration of communities dominated by false hellebore.  J. Range Mgmt. 57:365–370.  “False hellebore (Veratrum californicum Durand) is a native component of high-elevation, meadow-riparian areas of the mountain West that has increased due to historic heavy grazing. In 1991, a study was established in dense stands of false hellebore to evaluate mechanical and chemical control methods to reduce false hellebore and increase the abundance of the other native herbaceous species in these tall-forb communities. Four control methods consisting of the herbicide glyphosate (N-phenophonomethylglycine), mow, mowing in 2 consecutive years (remow), and tillage were used in 1991-1992. Each method was evaluated based on (1) reduction of false hellebore stem densities; (2) response of residual understory species; and (3) effectiveness of seeding a perennial grass and forb mixture to sustain initial treatment control. Stem density of false hellebore and nested frequency data for all species were collected in 1991, 1992, 1995, and 1999. The glyphosate treatment was effective in reducing false hellebore stem density which allowed for recovery of the remnant tall-forb community. The till treatment, while effectively reducing false hellebore stem density, also eliminated the other species in the community, leaving it open to invasive weeds. The mow and remow treatments did not reduce false hellebore stem density, but did allow for recovery of other components of the tall-forb community. Seeding following control treatments had no effect on false hellebore stem densities due to poor establishment. The mechanical treatments were generally more cumbersome in application and limited to gentle topography and well-drained sites without surface rocks. The application of herbicides is much easier and is adaptable to all types of terrain. The use of the herbicide glyphosate gave the best balance of false hellebore control and recovery of the tall-forb community.”

Cseri J., M. Dankó, L. Kovács, G. Szücs and E. Varga. 1980. Analysis of the sensitizing effect of veratrum alkaloids to potassium on frog muscle.  Acta Physiol. Acad. Sci. Hung. 56(3): 289–301. “The sensitizing effect of veratrum alkaloids to potassium is not specific. Reducing the concentration of chloride in Ringer's solution, or treating the muscle with nicotine in a concentration close to threshold after pretreatment with subliminal concentration of cevadine result in a marked mechanical response of the muscle. However, cevadine does not alter the sensitivity of the muscle to caffeine. On the basis of these observations it has been suggested that veratrum alkaloids sensitize the muscle membrane essentially to depolarizing processes. 2. Cevadine, 0.01 mM, fails to depolarize the muscle membrane but increases the depolarizing effect of 10 mM potassium. The depolarizing effect of a reduction of the concentration of chloride from 120 mM to 30 mM is also increased in cevadine pretreated muscle. Cevadine pretreatment increases the depolarizing effect of nicotine, too. 3. The above sensitizing effects are unanimously Na-dependent. Accordingly there is no mechanical response and increased depolarization in muscles equilibrated in sodium-free (choline) Ringer's solution before the cevadine treatment. 4. On the basis of the present data it is suggested that the membrane, when sensitized by veratrum alkaloids, can be triggered by different depolarizing processes and the depolarization increases as the result of increased Na permeability. The increased depolarization at the threshold level becomes sufficient for the automatic regenerative processes of the action potential to develop which activate the contractile elements. However, the mechanical response is a prolonged contraction rather than a contracture, its long period being the result of a very slow repolarization caused by the well-known inhibitory effect of veratrum alkaloids on Na inactivation.”

Fluck H. and H. R. Hegi.  1956. [Studies on the alkaloids of the surface organs of Veratrum album L. I. Qualitative studies on the alkaloids of the leaves.] Pharm. Acta Helv. 31(9): 428–447. German.

Fluck H. and H. R. Hegi.  1960. [Studies on the alkaloids in the aerial organs of Veratrum album L. Part 3. Fluctuations in the alkaloid content of the aerial organs, especially the low-lying leaves, of Veratrum album L.] Pharm. Acta Helv. 35: 1–12.

Fuska J., A. Fusková, A. Vassová and Z. Votický.  1981. New substances with cytotoxic and antitumor effects. IV. In vitro effect of some veratrum alkaloids and their derivatives on leukemia P388 cells. Neoplasma 28(6): 709–714. “Some Veratrum alkaloids and their derivatives exhibited an in vitro cytotoxic effect on leukemia P388 cells, depending on the structure of the skeleton of the molecule, particularly on the type of the heterocycle attached to C-20. Veracintine and 20-(2-methyl-1-pyrrolin-5-yl)-4-pregnen-3-one, which proved to be the most effective, inhibited incorporation of uridine, and to a lesser extent that of L-valine into P388 cells fractions. After a brief reaction (15 min), these substances became irreversibly bound in the P388 cells and stopped their further in vitro proliferation. The cytotoxic effect of veracintine became enhanced by sublethal doses of tubercidine (phase of maximum lethality of G1).”

Keeler, R. F. 1978. Cyclopamine and related steroidal alkaloid teratogens: their occurrence, structural relationship, and biologic effects.  Lipids. 13(10): 708–715. “A spontaneous congenital deformity is produced in lambs whose dams consume Veratrum californicum on the 14th day of gestation. The deformity is generally expressed as cyclopia, cebocephaly, anophthalmia, or microphthalmia. This teratogenic effect is produced by certain steroidal alkaloid teratogens from the plant - most notably the compound cyclopamine. Cyclopamine is a C-nor-D-homo steroid with fused furanopiperidine rings E and F at right angles to the plane of the steroid because of spiro attachment at C-17 of the steroid. Among veratrum alkaloids, only those with an intact furan ring E were teratogenic in sheep, whereas those in which the peperidine ring is not rigidly positioned at right angles to the steroid were not. Many ruminants and laboratory animals are susceptible to the teratogen. It has wide species and tissue specificity and appears to have a direct effect on the embryo, not as a consequence of metabolic alteration of its structure nor as an indirect effect through a maternal influence. Other plant sources, notably potatoes, tomatoes, and eggplant contain related spirosolane steroidal alkaloids. Among naturally occurring spirosolanes, solasodine is teratogenic in hamsters, but neither tomatidine not diosgenin, the non-nitrogen containing analog of solasodine, is teratogenic. Results of these and other studies suggest that a basic nitrogen positioned alpha with respect to the steroidal plane and at appropriate distance beyond the D ring confers the teratogenicity on the molecule. Potato sprouts with high alkaloid content are teratogenic in hamsters, but tubers and peels are not.”

Keeler, R. F. and W. Binns   2005. Teratogenic compounds of Veratrum californicum (Durand). V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources Teratology 1: 5–10 (online). 0ôCyclopamine, and its glycoside alkaloid X, along with jervine and veratrosine, induced cyclopian malformations in offspring born to ewes ingesting these compounds on the fourteenth day of gestation. Other steroidal alkaloids with somewhat similar structures and various other steroidal compounds including certain hormones and steroidal sapogenins did not induce the malformation.”

 Klohs,M. W.,  M. D. Draper, F. Keller, S. Koster, W. Malesh and F. J. Petracek.  1953. The Alkaloids of Veratrum fimbriatum Gray. J. Am. Chem. Soc.; 75(20):  4925 - 4927. "A chemical investigation of Veratrum fimbriatum Gray has yielded two new hypotensively active germine esters, germanitrine (C39H6901lN), and germinitrine (C39H57011N), as well as neogermitrine, jervine and pseudojervine. In addition, the alkaloidal ester, veratroylzygadenine, previously isolated from Zygadenus venenosus Wats was found to be present in this species of Veratrum. On hydrolysis, the triester germanitrine affords germine, acetic acid, tiglic acid and (I)-a-methylbutyric acid. The hydrolysis of the triester germinitrine, yielded germine, acetic acid, tiglic acid and angelic acid. On methanolysis, germanitrine readily loses a labile acetyl group yielding germanidine."

Krayer O., S. M. Kupchan, C. V. Deliwla and B. H. Rogers. 1953. Studies on Veratrum alkaloids. XVIII. Chemical and pharmacological relations between Zygadenus and Veratrum alkaloids. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 219(5): 371–385.

Krupp H., L. Lendle and K. Stapenhorst.  1952.  [The use of nicotin and veratrum alkaloids as insecticides.]. Arzneimittelforschung 2(6): 258-62.

Kupchan S. M., J. C. Grivas, C. I. Ayres, L. J. Pandya and L. C. Weaver. 1961.  Veratrum alkaloids. XLVI. Structure-activity relationships in a series of analogs of the protoveratrines.  J. Pharm. Sci. 50: 396–403.

Kupchan, S. M.  1961. Hypotensive Veratrum ester alkaloids. J. Pharm. Sci. 50: 273–287.

Kupchan, S. M. and R. H. Nehnsler.  1961. Veratrum alkaloids.  XLIV. Structure-activity relationships in a series of synthetic hypotensive esters of protoverine.  J. Med. Pharm. Chem. ;3: 129–155.

Kutney J. P., J. Cable, W. A. Gladstone, H. W. Hanssen, E. J. Torupka and W. D. Warnock.  1968. The total synthesis of Veratrum alkaloids. I. Verarine. J. Am. Chem. Soc. 90 (19): 5332–5334.

Li, H-l., J. Tang, R-h. Liu, M. Lin, B. Wang, Y-f. Lv, H-q. Huang, C. Zhang, and W-d. Zhang. 2007. Characterization and identification of steroidal alkaloids in the Chinese herb Veratrum nigrum L. by high-performance liquid chromatography/electrospray ionization with multi-stage mass spectrometry.  Rapid Communications in Mass Spectrometry 21(6): 869–879. Electrospray ionization multi-stage mass spectrometry (ESI-MSⁿ) was performed to study the fragmentation behaviour of seventeen steroidal alkaloids (4 protoverine-type alkaloids, 10 germine-type alkaloids and 3 zygadenin-type alkaloids) from the Chinese herb Veratrum nigrum L. The MSⁿ spectra of the [M+H]⁺ ions for steroidal alkaloids provided a wealth of structural information on the substituted groups. In positive ion mode, the three types of alkaloids showed very different characteristic ions: m/z 436 or 418 for protoverine-type alkaloids; m/z 438, 420 or 402 for germine-type alkaloids; m/z 440 or 422 for zygadenin-type alkaloids. These fragments were used to deduce their mass spectral fragmentation mechanisms. Furthermore, the primary compounds in methanolic extracts of the herb of Veratrum nigrum L. were investigated by using liquid chromatography (LC)/ESI-MSⁿ. As a result, 21 steroidal alkaloids (5 protoverine-type alkaloids, 14 germine-type alkaloids and 2 zygadenin-type alkaloids) were selectively identified from 27 determined peaks. Eleven compounds were unambiguously identified by comparing with standard compounds and ten compounds were tentatively identified or deduced according to their MSⁿ data. Two of these compounds (xingangermine and deacetyl xinganveratrine) were found to be novel steroidal alkaloids. In addition, the chemical structures of two pairs of steroidal alkaloid isomers were deduced by comparing their fragment ions. Given the important structural information of known and unknown steroidal alkaloids in crude herbal extracts, this study is useful for identifying these types of steroidal alkaloids in crude materials rapidly and selectively.”

Li H-J., Y. Jiang and P. Li. 2006. Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the Liliaceae family.  Nat. Prod. Rep. 23: 735–752.

Liang G. Y. and N. J. Sun. 1984. [Chemical studies on active principles of Veratrum stenophyllum. III. Studies on the structure of beta 1-chaconine and the partial structures of stenophylline C and stenophylline D]. Yao Xue Xue Bao. 19(6): 431-436.

Liang G. Y. and N. J. Sun. 1984. [Chemical studies on active principles of Veratrum stenophyllum. II. Studies on the structure of a new blood pressure lowering agents--stenophylline A]. Yao Xue Xue Bao. 19(3): 190-194.

Liang G. Y.  1984. [Studies on the alkaloids of Veratrum genus]. Yao Xue Xue Bao. 19(4): 309-20.

Liao W.-J., Y.-M. Yuan and D.-Y. Zhang.  2007. Biogeography and evolution of flower color in Veratrum (Melanthiaceae) through inference of a phylogeny based on multiple DNA markers  Plant Systematics and Evolution 267:177–190. “Veratrum (Melanthiaceae) comprises ca. 27 species with highly variable morphology. This study aims to construct the molecular phylogeny of this genus to infer its floral evolution and historical biogeography, which have not been examined in detail before. Maximum parsimony, maximum likelihood, and Bayesian analyses were performed on the separate and combined ITS, trnL-F, and atpB-rbcL sequences to reconstruct the phylogenetic tree of the genus. All Veratrum taxa formed a monophyletic group, within which two distinct clades were distinguished: species with white-to-green perianth formed one highly supported clade, and the species with black-purple perianth constituted another highly supported clade. Phylogenetic inference on flower color evolution suggested that white-to-green perianth was a plesiomorphic state and black-purple perianth was apomorphic for Veratrum. When species distribution areas were traced as a multi-state character, parsimonious optimization inferred that Veratrum possibly originated in East Asia. Our study confirmed previous phylogenetic and taxonomic suggestions on this genus and provided a typical example of plant radiation across the Northern Hemisphere.”

Ma R., A. Ritala, K. M. Oksman-Caldentey and H. Rischer. 2006. Development of in vitro techniques for the important medicinal plant Veratrum californicum. Planta Med. 72(12): 1142–1148. “VERATRUM CALIFORNICUM (Liliaceae) is an important monocotyledonous medicinal plant which is the only source of the anticancer compound cyclopamine. An IN VITRO culture system for somatic embryogenesis and green plant regeneration of VERATRUM CALIFORNICUM was developed. Embryogenic calli were induced from mature embryos on induction medium. Five basal media supplemented with different growth regulators were evaluated for embryogenic callus induction, modified MS medium with 4 mg/L picloram showing the best result for embryogenic callus production. Fine suspension cell lines were established by employing friable embryogenic calli as starting material and AA medium and L2 medium as culture media. The suspension cell lines cultured in AA medium with 4 mg/L NAA appeared to be fresh yellow and fast growing. The suspension cells were cryopreserved successfully and recovered at a high rate. Green plants were regenerated from embryogenic calli maintained on solid medium with 73 % regeneration ability (green plants/100 calli) in 27-month-old culture. The IN VITRO plantlets contained the steroid alkaloids cyclopamine and veratramine. This IN VITRO system will form the basis for metabolic engineering of VERATRUM cells in the context of biotechnological production of pharmaceutically important secondary metabolites. DMSO:dimethyl sulfoxide fw:fresh weight NAA:naphthaleneacetic acid 2,4-D:2,4-dichlorophenoxyacetic acid picloram:4-amino-3,5,6-trichloro-2-pyridinecarboxylic acid dicamba:3,6-dichloro-2-methoxybenzoic acid.”

Maj J. [Investigations on Veratrum lobelianum Bernh.; Veratrum extracts.] 1955. Acta Pol. Pharm. 11(Suppl): 108-110. Polish.

Meilman E. Clinical studies on veratrum alkaloids. III. 1953. The effect of protoveratrine on renal function in man. J. Clin. Invest. 32(1): 80–89.

Meilman E. and O. Krayer.  1950. Clinical studies on veratrum alkaloids; the action of protoveratrine and veratridine in hypertension. Circulation. Feb;1(2):204-13.

Murray, M. P.  High elevations meadows and grazing.  1997.  Internatl. J. Wilderness 3(4):24–27.Abstract: “High elevation grazing of cattle and sheep is a legal activity in wilderness areas administered by the U.S. Forest Service (USFS) and Bureau of Land Management (BLM) and occurs in about one-third of the U.S. Wilderness System (USWS). General effects of grazing on species composition and soil properties are described based on reported findings for three extensive types of high elevation meadows-grass, herbaceous, and moist sedge. The challenge for wilderness managers is to keep grazing within limits that protect the naturalness of meadow ecosystems. In general, where excessive grazing occurs, shifts in species composition from preferred livestock forage to less desirable, nonpalatable, and exotic species is observed. Soils of each meadow type respond differently to grazing pressure, and careful management should reflect these differences. Suggestions are offered for careful control of livestock distribution, timing, and stock numbers in order to protect naturalness of high elevation wilderness meadows.”

Olney H. O.  1968. Growth substances from Veratrum tenuipetalum.  Plant Physiol 43(3):293-302. “Young leaves and buds of Veratrum tenuipetalum yielded non-indolic growth accelerators and inhibitors in the acidic ether fraction. The titer of accelerators decreased while the inhibitors increased as leaves matured. This was also true when comparing extracts of immature and fruiting inflorescences. Indole 3-acetic acid was at no time detected in leaf, bud, and inflorescence extracts but indole 3-acetyl-aspartic acid was readily recovered from all of these.The alkaline ether fraction of leaf base meristems, buds, roots, and rhizomes was rich in crystalline and amorphous alkaloids and phenolic acids. Reducing the quantity of major substances through crystallization, precipitation, and filtration permitted thin film chromatographic separation of the minor alkaloids and phenolic acids in the presence of the major ones. The unchromatographed mixture, and also certain of the purified major and minor alkaloids studied, strongly inhibited growth in germinating oat and winter rye seeds. In addition, profound changes in morphology and cytology of the seminal roots resulted. DNA disappeared partially to completely from affected tissue in 2 day germinated seeds.”

Ruskin, A. and J. A., Rider. Veratrum viride, bio-assayed, in treatment of essential hypertension. 1950. Tex. State J. Med. 46(2): 80-84.

Schaffner, U. D. Kleijn, V. Brown and H. Müller-Schärer. 2001. Veratrum album in montane grasslands: a model system for implementing biological control in land management practices for high biodiversity habitats. BiocontrolNews and Information 2001 22 (1): 19N – 28N.

Schep, L. J.; D. M. Schmierer and J. S. Fountain.  2006. Veratrum Poisoning.  Toxicological Reviews. 25(2): 73-78.  "Several species of the Veratrum genus are associated with toxicity in humans and animals. The principal toxins are steroid alkaloids; some have a modified steroid template, whereas others differ in their esterified acid moieties. These alkaloids act by increasing the permeability of the sodium channels of nerve cells, causing them to fire continuously. Increased stimulation, associated with the vagal nerve results in a reflex that causes the triad of responses known as the Bezold-Jarisch reflex: hypotension, bradycardia and apnoea. Clinically, various Veratrum extracts were marketed for clinical use as antihypertensive drugs, but because of their narrow therapeutic index were withdrawn from the market. Following the ingestion of Veratrum alkaloids, expected signs and symptoms include vomiting and abdominal pain, followed by cardiovascular effects such as bradycardia, hypotension and cardiac conduction abnormalities and death. Similar symptoms arise in other mammalian species ingesting these alkaloids; teratogenic effects may occur to the fetuses of animals that have grazed on Veratrum californicum. Treatment consists of supportive care, with an emphasis on haemodynamic stability with fluid replacement, atropine and vasopressors. The onset of symptoms occurs between 30 minutes and 4 hours, and the duration of the illness can range from 1 to 10 days; however, with prompt supportive care, patients typically make a full recovery within 24 hours.”

Shakirov, R., V. V. Kul'kova and I. Nakhatov. 1994. Alkaloids of Veratrum lobelianum, verdinine and 3,15-DI-O-(2-methylbutyroyl)germine.  Khimiya Prirodnykh Soedinenii 1: 100–104 [Chemistry of Natural Compounds 31(1): 79–85, 1995].  “The results are given of an investigation of the alkaloid composition of the epigeal part ofVeratrum lobelianum Bernh. Veralomidine, rubijervine, germinaline, and the new bases verdinine (1) and 3,15-di-O-(2-methylbutyroyl)germine (2) were isolated. The structures of (1) and (2) have been established on the basis of their physicochemical properties and transformations. This is the first time that veralomidine has been isolated from a plant.

Tang J., H-L. Li, Y-H. Shen, H-Z. Jin, S-K. Yan, R-H. Li, and W-D. Zhang.  2007. Four New Germine Esters from Veratrum dahuricum. Helvetica Chimica Acta 90(4): 769–775.  “Four new alkaloids, compounds 1-4, based on the germine (=4,9-epoxycevane-3,4,7,14,15,16,20-heptol; 5) framework, were isolated from the rhizomes of V. dahuricum, together with germine proper. The X-ray crystal structure of germine (5) was solved, and all compounds were characterized by circular dichroism, 1D- and 2D-NMR (1H,1H-COSY, DEPT, HSQC, HMBC), as well as HR-MS analyses.”

Taylor, C. A. 1956.  Alkaloid yields of Veratrum fimbriatum as influenced by site, season and other factors.  Econ. Bot. 10: 166–173. "Alkaloid content of Veratrum fimbriatum is much greater during rapid growth in early spring than the rest of the year.  Top growth at the expense of stored food reserves did not deplete alkaloids,.  Individual plants were in two categories regarding high or low percentage alkaloid producers."

Wilkins R. W., J. R. Stanton and E. D. Freis. 1949. Essential hypertension; therapeutic trial of veriloid, a new extract of Veratrum viride. Proc. Soc. Exp. Biol. Med. 72(2): 302–304.

Wolters B. 1970. [Antimicrobial activity of Veratrum alkaloids]. Planta Med. 19(2): 189–196.

Yasuhiro, T., T. Kukuchi, W. Zhao, J. Chen and Y. Guo. 1998. (+)-Verussurine, a New Steroidal Alkaloid from the Roots and Rhizomes of Veratrum nigrum var. ussuriense and Structure Revision of (+)-Verabenzoamine1. J. Nat. Prod. 61 (11): 1397–1399.  “Two minor steroidal alkaloids, 1 and 2, have been isolated from the roots and rhizomes of Veratrum nigrum var. ussuriense. Their structures have been determined by the use of spectral data as 7-O-acetyl-15-O-(2-methylbutyroyl)-3-O-veratroylgermine (1) and 15-O-(2-methylbutyroyl)-3-O-veratroylgermine (2). By spectral data comparison with verabenzoamine, the structure of the latter compound has been revised from the previously reported 7-O-acetyl-15-O-(2-methylbutyroyl)-3-O-veratroylgermine (1) to 15-O-(2-methylbutyroyl)-3-O-veratroylgermine (2). Accordingly, alkaloid 1 [7-O-acetyl-15-O-(2-methylbutyroyl)-3-O-veratroylgermine] must be new, and it was given the trivial name verussurine.”

Yagi, A. and T. Kawasaki. 1962. [Alkaloids of Japanese Veratrum genus plants. V. Alkaloids of Veratrum stamineum.] J. Pharmacol. 82: 210–213.

Youngken H. W. 1953. Studies on Veratrum. II. Veratrum eschscholtzii A. Gray; observations on seed germination and early growth of seedlings of Veratrum species. J. Am. Pharm. Assoc. Am. Pharm. Assoc. (Baltim.) 42(1): 39-45.

Youngken H. W. 1952. A pharmacognostical study of roots of different species of Veratrum. J. Am. Pharm. Assoc. 41(7): 356-361.

Zhao W., Y. Guo, S. Wang, T. Shao, Y. Tezuka and T. Kikuchi.  1998. [Chemical research on stilbenes from Veratrum macckii Reg.]. Zhongguo Zhong Yao Za Zhi. 23(10): 619–620, 640.“OBJECTIVE: To study the components in rhizome of Veratrum macckii. METHODS: Column chromatography and preparative thin layer chromatography with silica gel were employed for the isolation and purification of constituents. The structures were elucidated by IR, MS and 1H-NMR analysis. RESULTS: Two compounds were obtained and elucidated as resveratrol and 2,3',4,5'-tetrahydroxystilbene. CONCLUSION: The two compounds were separated from V. macckii for the first time.”

Zhao, W., W. Hao, Y. Tezuka,  T. Kikiuchi,  J. Chen and Y. Guo. 1991. Studies on the Constituents of Veratrum Plants. II. Constituents of Veratrum nigrum L. var. ussuriense. (1). Structure and ¹H-and ¹³C-Nuclear Magnetic Resonance Spectra of a New Alkaloid, Verussurinine, and Related Alkaloids. Chem. & Pharm. Bull. (Pharm. Soc. Japan): 39(3): 549–554. “Alkaloidal constituents of the roots and rhizoma of Veratrum nigrum L. var. ussuriense (Liliaceae), which are used as a source of the Chinese crude drug "Li-lu, " were examined and a new alkaloid named verussurinine and six known alkaloids have been isolated. The structure of verussurinine was determined to be 16-O-(2-methylbutyroyl)germine (1) by means of spectroscopic methods, and six other alkaloids were identified as germidine (2), germerine (3), 15-O-(2-methylbutyroyl)germine (4), verazine (5), jervine (6), and neogermbudine (7), Complete assignments of the proton and carbon-13 nuclear magnetic resonance (^1H- and ^<13>C-NMR) signals of these alkaloids are also presented.

Zhou C-X., J-Y. Liu, W-C. Yeb, C-H Liu and R-X. Tan. 2006. Neoverataline A and B, two antifungal alkaloids with a novel carbon skeleton from Veratrum taliense. Tetrahedron 59(30): 5743–5747. “Bioassay-guided fractionation of the ethanol extract of the roots and rhizomes of Veratrum taliense yielded two new and thirteen known steroidal alkaloids. The structures of the two new compounds, neoverataline A and B, were established by extensive spectroscopic analyses to be 3,4-secocevane-4,9-olid-14,15,16,20-tetra-ol-3-oic acid and 3,4-secocevane-4,9-olid-7,14,15,16,20-penta-ol-3-oic acid, respectively, and are a novel carbon skelton. All of the fifteen alkaloids were subjected to in vitro antifungal assays, which showed that the verazine- (veramitaline, stenophylline B, stenophylline B-3-O-β--glucopyranoside, veramiline-3-O-β--glucopyranoside) and jerveratrum-type (jervine, jervine-3-O-β--glucopyranoside) alkaloids exhibited strong antifungal activities against the phytopathogenic fungus Phytophthora capisis with MICs of 160, 120, 160, 80, 80 and 120 μg·L⁻¹, respectively. Furthermore, the verazine-type alkaloids stenophylline B, stenophylline B 3-O-β--glucopyranoside and veramiline 3-O-β--glucopyranoside were shown to also inhibit the growth of another fungal phytopathogen Rhizoctonia cerealis with MICs of 160, 120 and 120 μg mL⁻¹. The MICs of triadimefon (an antifungal agrochemical used herein as a positive control) against P. capisis and R. cerealis were 120 and 80 μg mL⁻¹, respectively. A preliminary structure–activity relationship regarding these alkaloids has been formulated. ”

Zhou C. X., J. Tanaka, C. H. Cheng, T. Higa and R. X. Tan.  1999.  Steroidal Alkaloids and Stilbenoids from Veratrum taliense.  Planta Med. 65(5): 480–482. “Phytochemical investigation of roots and rhizomes of Veratrum taliense yielded a new and six known steroidal alkaloids as well as a new and one reported stilbene derivative. By a combination of spectral methods (IR, MS, (1)H- and (13)C-NMR, COSY, HMQC, HMBC, and NOESY), the structure of the new alkaloid was established as 15-angeloylgermine while the known ones were identified as 15-(2-methylbutyroyl)germine, jervine, 3-veratroylzygadenine, germine, veramiline 3- O-(beta- D-glucopyranoside and stenophylline B-3- O-beta- D-glucopyranoside. The new stilbenoid, named veraphenol, was determined to be 2-(3',5'-dihydroxyphenyl)-6-hydroxybenzofuran, and the known one was shown to be resveratrol. The IN VITRO enzyme assay indicated that 3-veratroylzygadenine and resveratrol are inhibitors of xanthine oxidase. The enzyme inhibitory action of resveratrol, the most active compound found so far in V. TALIENSE, is dose-dependent with the IC (50) value at 30 microM (the IC (50) value of allopurinolused as a positive control in the study is 10 microM).”

Zimmerman J. H. 1958. A monograph of Veratrum. Ph.D. dissertation, University of Wisconsin, Madison, Wisconsin, USA.

Zomlefer, W. B., W. M. Whitten, N. H. Williams and  and W. S. Judd.  2003. An Overview of Veratrum s.l. (Liliales: Melanthiaceae) and an Infrageneric Phylogeny Based on ITS Sequence Data. Syst. Bot. 28: 250–269. “A synopsis of Veratrum, including commentary on species and character evolution within the genus, is presented. The circumscription and relationships of infrageneric taxa are evaluated using parsimony analyses of ITS (nuclear ribosomal) DNA sequence data of 26 representative taxa. Proposed new infrageneric circumscriptions, strongly supported by tree statistics and topologies, are correlated with potential morphological synapomorphies at the proper level of universality. Based on our analyses, Veratrum is circumscribed broadly (including Melanthium) and divided into two sections and two subsections (most with novel circumscription). This modified infrageneric classification involves reassignment of Veratrum subgenus Pseudoanticlea as subsection Pseudoanticlea. Although interspecific relationships are not highly resolved, the molecular data provide strong support for placing several species previously of unknown affinities and also validate several generalizations concerning character evolution within Veratrum.”

 Zomlefer, W. B., N. H. Williams, M. Whitten and W. S. Judd.  2000.  Generic circumscription and relationships in the tribe Melanthieae (Liliales, Melanthiaceae), with emphasis on Zigadenus: evidence from ITS and trnL-F sequence data.  “The circumscription and relationships of genera within the tribe Melanthieae (29 representative taxa) were evaluated using parsimony analyses of ITS (nuclear ribosomal) and trnL-F (plastid) DNA sequence data, alone and in combination. Proposed new generic circumscriptions, strongly supported by the tree statistics and topologies in all analyses, are correlated with potential morphological synapomorphies at the proper level of universality. Based on the molecular cladograms, Stenanthium is biphyletic, and the traditional Zigadenus s.l. (sensu lato) is polyphyletic. Amianthium and Schoenocaulon are distinct entities; the Veratrum complex is conservatively treated as one large monophyletic genus (including Melanthium). Although some generic relationships are not highly resolved, the analyses provide strong support for Zigadenus glaberrimus as sister to the rest of the tribe, and Amianthium muscitoxicum as closely related to Veratrum s.l. As a result of these analyses, seven genera (some with novel circumscription) are recognized within the tribe Melanthieae: Amianthium, Anticlea, Schoenocaulon, Stenanthium, Toxicoscordion, Veratrum, and Zigadenus.”

Related Articles:

Neuss, N., A new alkaloid from Amianthium muscaetoxicum Gray. Journal of the American Chemical Society, 1953. 75: p. 2772-2773.

Zomlefer W. B. 1997a The genera of Melanthiaceae in the southeastern United States. Harvard Papers in Botany 2: 133-177.

USDA ARS Procurement of Plant Samples for Veratrum californicum

1. USDA ARS Record of Plant Procurement for Veratrum californicum from California
2. USDA ARS Record of Plant Procurement for Veratrum californicum from Colorado
 

The links to two "pdf" files listed above show photocopies of "active sheets" with collection and activity data noted by personnel of the USDA Agricultural Research Service (ARS), New Crops Research Branch, Plant Science Research Division.  A record ("active sheet") for Veratrum californicum was created as a result of activity reported by the National Cancer Institute (NCI) in  samples of Veratrum californicum. 

Brief Explanation as to what the fields and notations mean.

QNS: Quantity Not Sufficient: Additional material is required for confirmation of antitumor activity.

DN: Deferred due to insufficient activity

WM (or WA): Walker carcinosarcoma 256, in vivo

Records on Active Plants from California and Colorado: Veratrum californicum

Active Sample:  The B is a standard abbreviation assigned by the ARS to collections made by Arthur S. Barclay followed by his collection number for the voucher specimen deposited in the U.S. National Arboretum in Washington, DC (NA).  Similarly, P designates collections made by Robert E. Perdue, Jr.  Collector's abbreviation codes only appear on USDA accession records (shipping lists), not on the labels of voucher specimens.  The shipping lists were prepared after samples were dried and shipped to the headquarters office.  Each voucher specimen was identified after the collection was made.  Samples for each collection were subsequently assigned an unique (accession) number—a PR (Project Resource) number.  The other B number—that appears—is the extract number that showed confirmed activity in WM, reported August 12, 1968; it is a standard abbreviation used by NCI for natural product extracts.

Although the first sample accessioned from this species was that collected by Dr. Perdue from Colorado in Sep.1962 (PR 4626), it was not  the first sample of Veratrum californicum collected by the ARS for the NCI.  Dr. Arthur Barclay had independently collected a sample several months earlier (B-1376) from California, July (1962).   Dr. Barclay's sample was probably accessioned later because he had collected more samples in his field trip that would have required more time to assemble and identify.

The Barclay sample that was active in the tumor WA consisted of dried stem-leaf (st-lf), weighing 1.75 pounds.  It was collected in Siskiyou County, California on Mt. Shasta, July 1962. On the other hand, the Perdue sample that was reported to have preliminary antitumor activity consisted only of root that was collected in Colorado on May 4, 1964.  The assay used for the Colorado sample is not indicated, but a notation below—.41 and .47—appears to be KB data, although it could also be SA or LL.  It might be added that an NCI cumulative record of confirmed activity on plant and animal products screened shows only WA (WM).  Thus, a preliminary report may have been submitted by Monroe Wall based on testing in KB.

Recollections: For California, two recollections are noted, one, T-4196, is indicated to have included14 pounds of st-lf (stem-leaf) from California; the T is for Dr. Edward Terrell, an employee of the ARS, the sample was reportedly collected in August 1968; his voucher would be at NA.  The second recollection, also from California, included 43 pounds of st-lf-fl-fr (stem-leaf-flower-fruit. combined).  It was reportedly collected in September 1970 and referenced by M-3418.  The M is for Miscellaneous, a prefix and number assigned by the ARS to collections that were not routine. However, this recollection was actually made by Richard Spjut—who at the time was in his second year of collecting for the ARS/NCI.  His sample of Veratrum californicum was collected on July 18, 1970 from near Mt. Shasta.  He was assisted by Ken Miles, a student of optometry, now an Optometrist at Kaiser in Napa, CA. Spjut at the time was a student at Humboldt State University.  He collected samples for the USDA/NCI antitumor screening program under contract.  His collection number was not the M-number assigned by the ARS, but his collection number—444—that appears on the herbarium label; later, when employed by the ARS, his collection numbers were given the prefix SPJ, which were not assigned any M number.  His voucher—sent to the ARS in Beltsville MD and deposited at the NA in Washington DC—may not have the M-number (M-3418).  The record of Miscellaneous collections were kept separate from the others and were probably trashed in Oct. 1982 with the reference samples.  The only exception to a link between the M-numbers on the shipping list (and in the NCI database) are rare cases where a former late botanist at the ARS lab in Beltsville, Lloyd Spetzman, added the PR number to the voucher labels before sending them off to the National Arboretum.

The source “Kup” is not really a source but the fractionating chemist, Morris Kupchan  (Dept. of Chemistry, University of Virginia) who was assigned to isolate active agents from Veratrum californicum by Jonathan Hartwell, the Chief of the Natural Products Division at the National Cancer Institute.

For Colorado, only one recollection is indicated, 33 lbs of bulb-stem, sent to Monroe Wall, at Research Triangle Institute in North Carolina.

As indicated above, this situation of having two chemists independently working on the same species was unusual as Dr. Hartwell had made every effort to avoid this.  But a conflict was not readily apparent because technically there was only one active collection reported—that was assigned to Dr. Kupchan.  Dr. Wall, on the other hand, may have been trying to get ahead on discovering novel active compounds as he had done for camptothecin, which was discovered as a result of his following up on a preliminary active report.

Additional notations (below the recollection line).  Low priority—indicated because the recollection obtained by Ed Terrell failed to confirm in KB or WM, while the 14 pounds supplied was probably sufficient for any further testing.  However, Spjut had received a letter from  Perdue asking for 50 pounds of Veratrum californicum (dried).  An additional notation, dated April 1971, indicated PS (P-388 leukemia) activity.  This would appear to be from Spjut's sample, which may have been reported by Kupchan (by letter or by phone) since there is no record of such activity in the NCI active plants (CPAM, 1976, 1981).

The Cumulative Plant And Animal (CPAM) listing for antitumor activity, published yearly by the NCI, with monthly updates sent to cooperating research parties, indicated only WA activity in Veratrum californicum.  One other species, Veratrum nigrum was reportedly active in KB from a root sample collected in Taiwan.

Some additional Codes in other data sheets on active species.

DK:  Dropped due to known compound.

LL:  Lewis Lung

SA: Sarcoma 180