Veratrum alkaloids are a class of natural compounds found in plants of the Veratrum genus.Historically,Veratrum has been used as a source of medicines and insecticide. Their toxicity was noted in sneezing powders made from pulverized roots of these plants. Inhalation or ingestion has resulted in several signs and symptoms, including hypotension or bradyarrhythmia.
Pharmacological and toxicological
studies on Veratrum alkaloids have revealed pharmacological effects such as
lowering blood pressure, strengthening the heart, anti-thrombotic, improving
blood-brain circulation, and antiparasitic infection. However, it has been
found to have both reproductive and genotoxic effects and significant toxic
effects on the human digestive and respiratory systems, so it should not be
used indiscriminately.
Mechanism
of Toxicity[1]
The veratrum alkaloids, which are
chemically similar to steroids, include protoveratrine, veratridine, and
Jervine. These agents were introduced in the 1950s as antihypertensive agents;
however, they were found to have a narrow therapeutic index, and their use was
discontinued.
Of these steroidal alkaloids, veratridine
is the most potent. The primary activity of these compounds is to attach to
voltage-sensitive sodium channels in conductive cells and increase sodium
permeability, raising intracellular sodium concentration like grayanotoxins.
Veratrine affects only a limited number of the sodium channels, but those
affected reactivate 1000 times more slowly than the unaffected channels (i.e.,
slow recovery).
These alkaloids also appear to block the
inactivation of sodium channels and change the activation threshold of the
sodium channels so that some remain open. Again, the rise in intracellular
sodium concentrations leads to increased automaticity and enhanced vagal tone.
Again, the rise in intracellular sodium concentrations leads to increased
automaticity, improved vagal tone without hyperkalemia, and occasional
neurotoxicity.
Toxicology studies can provide a
comprehensive and systematic safety evaluation of a drug and elucidate its
mechanism of toxicity to reduce the risk to human health. Toxicological
studies on Veratrum alkaloids aim to understand the mechanisms of their
toxicity, identify the toxic effects they produce, and evaluate the potential
risks associated with their use. These studies have been conducted in vitro and
in vivo, using different animal models and experimental approaches.
1,Acute toxicity test of Veratrum alkaloids
(1) Mice orally dosed with raw quinoa
1.8/kg, a small number of animals died when value-added 3.6g/kg, the mortality
rate of 60%; injected with 1% quinoa solution 0.5ml, all died within 15
minutes.
(2) In Cats orally administered with
0.66g/kg of quinoa, a small number of animals died, and at 1.39g/kg, half died.
(3) Tianmu quinoa is very toxic, and its
LD50 is similar to daylily root, but there is no accumulation of poisoning
phenomenon.
It has also been reported that the LD50 of
above-ground parts of quinoa is 124.45g/kg, and the rhizome is 6.7g/kg. The
subcutaneous injection of black quinoa leachate ld50 in mice was 1.78g/kg, the
subcutaneous injection of time quinoa alkaloids LD50 in mice was 26mg/kg, and
the intravenous infusion LD50 was 3.2mg/kg.
2,Toxicological effects of Veratrum
alkaloids
The toxicological study found that quinoa
crude extract has an evident and long-lasting hypotensive effect on
anesthetized dogs or cats, without a rapid tolerance phenomenon, accompanied by
slowed heartbeat, respiratory depression, or even suspension while lowering
blood pressure also has a hypotensive effect on dogs with renal
hypertension.
The hypotensive principle of Veratrum
alkaloids is thought to be due to the reflex inhibition of vasomotor centers by
sinus nerves and vagal afferent fibers in the carotid sinus and
cardio-receptive areas, causing a decrease in blood pressure.
However, the whole plant is toxic, and the
toxins are mainly alkaloids contained in it. Among them, protoveratrine is the
most toxic, followed by Jervine. The poisoning of Veratrum is usually acute.
Veratrum alkaloids have apparent poisonous effects on the nervous, respiratory,
cardiovascular, digestive, etc.
Primary mechanisms of poisoning.
(1) Veratrum strongly irritates the mucous
membrane of the digestive tract, causing nausea, vomiting, and inflammation of
the esophagus and gastrointestinal tract.
(2) Veratrum alkaloids act on the central
nervous system, causing the brain to become excited and then inhibited,
resulting in spasms, convulsions, and symptoms of drowsiness and coma.
(3) Veratrum alkaloids stimulate the vagus
nerve nucleus in the brain, causing increased excitability of the vagus nerve,
resulting in a decrease in blood pressure, slowed heart rate, irregular heart
rate, profuse sweating, increased intestinal peristalsis, and respiratory
depression. Veratrum alkaloids also have reproductive toxicity, genotoxicity,
and a narrow safety window. The pharmacology, toxicology, and mechanism of
action of Veratrum alkaloids in combination application must be studied more
thoroughly.
Veratrum alkaloids are the main toxic
components of the poisonous plant quinoa. Some Toxicological studies on Veratrum
alkaloids have found that the therapeutic and poisoning doses of quinoa
alkaloids are very close to each other while treating diseases.
Suppose we can clarify the molecular
mechanism of the pharmacological and toxicological effects of Veratrum
alkaloids. In that case, we can avoid harm and provide an essential basis for
developing new drugs.
[1] Mauro Cataldi, in xPharm: The
Comprehensive Pharmacology Reference, 2010[J]
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