Hellebore

Scientific Name(s): Veratrum album L., V. viride Ait., V. californicum Dur, V. nigrum L., V. fimbriatum A. Gray, V. frigidum Schltdl. and Cham 1 , 2 Family: Liliaceae

Common Name(s): White hellebore , langwort , green hellebore , false hellebore , itchweed , Indian poke , California false hellebore , Western hellebore , black false hellebore , fringed false hellebore

Uses

Hellebore has been used to treat high blood pressure. However, research reveals no clinical trials regarding the use of veratrum for any condition.

Dosing

White hellebore is extremely toxic, with classical doses in the range of 0.02 to 0.1 g of powdered root. Its hypotensive properties are not considered therapeutically useful. 3

Contraindications

No longer considered safe.

Pregnancy/Lactation

Documented adverse effects. Avoid use.

Interactions

None well documented.

Adverse Reactions

Hellebore is irritating and ingestion can result in a burning sensation in the upper abdominal area followed by salivation, vomiting, gastric erosion, hypotension, and bradycardia.

Toxicology

There have been several poisoning reported in humans with the different species, but all had favorable outcomes.

Botany

Included among its approximately 30 species are the following:

Veratrum album or white hellebore (WH) is a perennial that has a wide distribution throughout Europe, northern Asia, and North America. It grows to 5 feet and is characterized by a hairy stem. Its large, oval, yellow-green leaves alternate around the stem and have a slightly hairy undersurface. The lower leaves can reach a foot in length. Its greenish flowers bloom in June and July. The rhizome has an acrid taste and onion-like odor. The fruit is a capsule. 4

Veratrum viride or green hellebore (GH) can grow to 8 feet in height and is found in damp areas such as marshes and swamps. It has oval to linear leaves, with green flowers on short stalks. Its habitat is northern North America, west of the Rockies. 5 The dried rhizome is the part of the plant used. 6 The plant's flowers are greenish yellow in color. 2

WH resembles GH in structure and appearance (ie, similar leaves), 2 although its external color is much lighter. 6 The rhizomes of the 2 species are histologically, chemically, and toxicologically similar. WH may be more poisonous and contain more alkaloids than GH. 2

History

Veratrum comes from the Latin vere meaning “truly,” and ater meaning “black.” In 1900, both species ( V. album and V. viride ) were recognized. 2

The use of V. album centers around its toxic potential. It had been used as a poison during Roman times and an extract of the plant was used as an arrow tip poison. Small doses had been used to treat symptoms of cholera, often with less than desirable effects. White hellebore had been used in place of Colchicum for the treatment of gout, to aid in the treatment of hypertension, and externally to treat herpetic lesions, but its use has always been limited by its toxicity.

Green hellebore was used by certain Indian tribes to treat congestion and arthritic pain. European settlers used the plant as a delousing agent. Like WH, GH is also highly toxic and rarely used in herbal medicines today in except homeopathy. 5

Chemistry

Important alkaloids of both species in general include esters of highly hydroxylated parent alkanolamine bases, mainly cervine, germine, and protoverine. Other alkanolamines include jervine, rubijervine, pseudojervine, and isorubijervine. Alkaloids present in both species include veratrobasine and geralbine. 2 Veratrum alkaloids (cyclopamine, cycloposine, jervine, and veratramine) have been evaluated by carbon-13 and proton nuclear magnetic resonance spectra analyses. 7 Analysis of jervine from Veratrum species has also been performed using densitometry, thin layer, and liquid chromatography methods. 8 In addition, alkaloids from 17 species of veratrum have been identified and reviewed. 9 , 10

White hellebore has been found to contain 2 related alkaloids, protoveratrine A and B. The rhizome contains about 1.5% total alkaloids, which also include germerine, jervine, pseudojervine, and veratrosine. 11 Minor and other alkaloids have been described. 12 , 13 Non-alkaloidal compounds also have been isolated from WH “above ground” parts and include cinnamic, isoferulic, caffeic, chlorogenic, fumaric, and succinic acids, and tectochrysin. 14 Organic acids veratric and vanillic are also present. 15 Other reports concerning WH-specific chemistry include: Phenolic compounds from aerial plant parts, 16 isolation of flavonoids chrysoeriol and apigenin, 17 determination of beta-adrenoceptor agonist, “o-acetyljervine,” 18 and identification of glycoside veratramarine. 19

Three alkaloid groups are present:

  • Esters of steroidal bases (alkamines) with organic acids, including cevadine, germidine, germitrine, neogermitrine, neoprotoveratrine, protoveratrine, and veratridine;
  • The glucosides of the alkamines pseudojervine and veratrosine;
  • The alkamines themselves including germine, jervine, rabijervine, and veratramine. 6 , 20
Alkaloid mixtures alkavervir and cryptenamine are also specifically mentioned as being constituents in WH. 21

Other Veratrum species chemistry is available, including vertaline B structure from V. taliense , 22 steroidal alkaloid isolation from V. californicum , 23 isolation of alkaloids verazine and angeloylzygadenine from V. maacki , 24 and isolation of a new indole alkaloid echinuline from V. nigrum . 25

Uses and Pharmacology

Hypertension

The white and green varieties of veratrum have been used for their antihypertensive properties. 6 , 26 , 27 , 28

Animal data

Protoveratrines caused prompt improvement of cardiac and respiratory functions in rats suffering from severe hypotension and respiratory depression, warranting further experimentation in the area of such crisis management as massive blood loss, etc. The mechanism could be attributable to an increase in total peripheral resistance and cardiac output. 29

Clinical data

When administered intravenously, protoveratrine A and B cause a rapid reduction in blood pressure. Protoveratrine A is more active orally than B. Extracts of this plant have sometimes been combined with rauwolfia alkaloids in the treatment of hypertension. 30 Some alkaloids of Veratrum species exhibit a cardiotonic, digitalis-like effect. 10 Other sources report the ester alkaloids to reduce systolic and diastolic pressure, slow the heart rate, and stimulate peripheral blood flow. 2 , 20 Large doses of plant extracts may cause respiratory depression. Neurophysiological studies show certain alkaloids of GH work on the pacemaker area of the heart, and are of possible use in management of tachycardia or fibrillations. 2 However, the use of veratrum derivatives in the 1950s for hypertension therapy diminished with the discovery of more effective agents in the 1960s. 31

Other uses

Other actions of hellebore include stimulation of cardiac receptors, inhibiting ADH secretion in dogs, 32 and possible serotonin-agonist actions of constituent veratramine. 33

Certain veratrum alkaloids exhibit in vitro cytotoxic effects on leukemia cells. 34 A later report discusses the demonstration of hemolytic and cytotoxic effects of the alkaloids. 35

At least 1 report is available discussing a synthetic veratrum derivative and how it may be of use in myasthenia gravis treatment. 36

Veratrum species have also been used as insecticides. 6 , 20 One report on V. album discusses its insecticidal activity against Drosophila , Tribolium , and Aedes species. 37

Other uses for veratrum include treatments for cancers, respiratory problems, convulsions, mania, neuralgia, headaches, analgesia, inflammations, fluid retention, vomiting, toothache, amenorrhea, hiccoughs, measles, and sunstroke. 20

Other Veratrum species literature is available concerning antiplatelet principles of V. formosanum , 38 absorption studies of V. nigrum , 39 and hemodynamic effects of V. nigrum . 40

Dosage

White hellebore is extremely toxic, with classical doses in the range of 0.02 to 0.1 g of powdered root. Its hypotensive properties are not considered therapeutically useful. 3

Pregnancy/Lactation

No longer considered safe.

Interactions

None well documented.

Adverse Reactions

Hellebore is irritating and ingestion can result in a burning sensation in the upper abdominal area followed by salivation, vomiting, gastric erosion, hypotension, and bradycardia.

Toxicology

All Veratrum species are irritating; 20 however, V. album -specific poisonings have been the most often observed. For example, 7 cases have been reported to the Austrian Poison Information Center from 1977 to 1981. 41 Usual symptoms include hypotension, bradycardia, and gastrointestinal distress. 20 , 21 , 42 One source suggests ingestion of the alkaloids causes a burning sensation in the upper abdominal area followed by salivation, vomiting, and gastric erosion. Symptoms have been described as “having a heart attack.” However, symptoms often disappear within 24 hours. 43

Stereochemical configuration of veratrum alkaloids offer reason for the plant's teratogenicity. 44 Parasympathetic stimulation and increase in the permeability of sodium channels also contribute to its toxic mechanisms. 4

Inhalation of the powdered rhizome induces a runny nose and violent sneezing. 45 Seven cases of intoxications have been reported from V. album alkaloids present in sneezing powder. 46 The fatal human dose of powdered rhizome is 1 to 2 g. 19

Five cases of V. album poisoning have been reported, all having occurred shortly after ingestion of what was believed to be gentian wine (homemade; V. album was mistaken for Gentiana lutea when harvested because of similarities in appearance and habitat). Clinical effects included nausea, vomiting, abdominal pain, hypotension, and bradycardia. Therapy with atropine led to recovery within a few hours. 47 Another case of “mistaken identity” of V. album with G. lutea describes similar gastrointestinal and cardiac symptoms. 48

Two additional V. album poisonings have occurred within 30 minutes of ingestion. Symptoms included vomiting, decrease in blood pressure, and bradycardia. Both cases had favorable outcomes. 49

Six cases of V. viride poisonings have been reported, the symptoms being similar to those of V. album toxicity. 50

Congenital tracheal stenosis occurred in 7 of 9 lambs born to 6 ewes who ingested the related species V. californicum . All 7 died from asphyxia within 5 minutes after birth. 51 Poisoning by this species is a veterinary problem in the US.

Bibliography

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