Toxicological studies on Veratrum alkaloids

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]