Senecionine is a toxic

pyrrolizidine alkaloid Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect he ...

isolated from various botanical sources. It takes its name from the ''

Senecio ''Senecio'' is a genus of flowering plants in the daisy family (Asteraceae) that includes ragworts and groundsels. Variously circumscribed taxonomically, the genus ''Senecio'' is one of the largest genera of flowering plants. Description Morp ...

'' genus and is produced by many different plants in that genus, including ''

Jacobaea vulgaris ''Jacobaea vulgaris'', syn. ''Senecio jacobaea'', is a very common wild flower in the family Asteraceae that is native to northern Eurasia, usually in dry, open places, and has also been widely distributed as a weed elsewhere. Common names inc ...

'' (''Senecio jacobaea''). It has also been isolated from several other plants, including '' Brachyglottis repanda'', ''

Emilia Emilia may refer to: People * Emilia (given name), list of people with this name Places * Emilia (region), a historical region of Italy. Reggio, Emilia * Emilia-Romagna, an administrative region in Italy, including the historical regions of Emi ...

'', ''

Erechtites hieraciifolius ''Erechtites hieraciifolius'' (fireweed, American burnweed, or pilewort) is a plant in the daisy family, Asteraceae. It is native to the Americas, but is found many places around the world having been introduced by human activity. It is introduce ...

'', ''

Petasites ''Petasites'' is a genus of flowering plants in the sunflower family, Asteraceae, that are commonly referred to as butterburs and coltsfoots.Syneilesis'', ''

Crotalaria ''Crotalaria'' is a genus of flowering plants in the family Fabaceae (subfamily Faboideae) commonly known as rattlepods. The genus includes over 700 species of herbaceous plants and shrubs. Africa is the continent with the majority of ''Crotalar ...

'', '' Caltha leptosepala'', and ''

Castilleja ''Castilleja'', commonly known as paintbrush, Indian paintbrush, or prairie-fire, is a genus of about 200 species of annual and perennial herbaceous plants native to the west of the Americas from Alaska south to the Andes, northern Asia, and one ...

''. The compound is toxic and consumption can lead to liver damage, cancer, and

pyrrolizidine alkaloidosis Pyrrolizidine alkaloidosis is a disease caused by chronic poisoning found in humans and other animals caused by ingesting poisonous plants which contain the natural chemical compounds known as pyrrolizidine alkaloids.''The Merck Veterinary Manual''. ...

. Because of this, consumption of plants that produce it has resulted in

poisoning A poison can be any substance that is harmful to the body. It can be swallowed, inhaled, injected or absorbed through the skin. Poisoning is the harmful effect that occurs when too much of that substance has been taken. Poisoning is not to ...

s, both in humans and in animals.

Toxicity

Like other pyrrolizidine alkaloids, senecionine is toxic when ingested. The ingested molecule is a

protoxin Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as we ...

that is metabolized to its active form. In large quantities, ingestion can lead to critical illness, including convulsions and death. Studies in rodents have shown an LD₅₀ of 65 mg/kg. In smaller, non-lethal quantities, ingestion can lead to

intoxication Intoxication — or poisoning, especially by an alcoholic or narcotic substance — may refer to: * Substance intoxication: ** Alcohol intoxication ** LSD intoxication ** Toxidrome ** Tobacco intoxication ** Cannabis intoxication ** Cocaine i ...

, although clinical signs and symptoms may not present until months after exposure depending on the level of exposure. Ingestion can lead to both

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and DNA damage.

Liver toxicity

The liver damage in both acute and chronic intoxication can cause

hepatic veno-occlusive disease Hepatic veno-occlusive disease (VOD) or veno-occlusive disease with immunodeficiency is a potentially life-threatening condition in which some of the small veins in the liver are obstructed. It is a complication of high-dose chemotherapy given bef ...

(VOS), signs and symptoms of which include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...

, and bloody

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

. Additionally, acute intoxication can cause hemorrhagic

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

and liver failure, with signs and symptoms including

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

, depression, behavior changes, and

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, ab ...

Photosensitive Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...

dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can v ...

may also be seen. Other symptoms and manifestations of chronic exposure include

weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

portal hypertension Portal hypertension is abnormally increased portal venous pressure – blood pressure in the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient gr ...

, and

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

DNA damage

Senecionine ingestion can also induce DNA damage. Although there are few if any cases of human cancers directly linked to senecionine intoxication, rodent studies have shown that it is capable of inducing tumor formation in the liver,

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

, and gastrointestinal tract.

Diagnosis

Diagnosis of senecionine toxicity is made based on

history History (derived ) is the systematic study and the documentation of the human activity. The time period of event before the History of writing#Inventions of writing, invention of writing systems is considered prehistory. "History" is an umbr ...

physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...

, and

liver biopsy Liver biopsy is the biopsy (removal of a small sample of tissue) from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment. Medica ...

. Lab findings may include increased

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...

concentrations,

hyperbilirubinemia Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

hypoproteinemia Hypoproteinemia is a condition where there is an abnormally low level of protein in the blood. There are several causes that all result in edema once serum protein levels fall below a certain threshold. Causes # Nutritional hypoproteinemia is due ...

, and abnormal

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

(LFTs). However, it has been observed that chronically exposed animals may have normal lab values for months to years despite ongoing liver damage.

Histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

abnormalities on biopsy include megalocytosis, necrosis, fibrosis, and

biliary A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...

, similar to other hepatotoxic ingestions and

immune system disorders An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...

Other Bioactivity

Senecionine has also been evaluated as an

anti-microbial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals a ...

. A cocktail of pyrrolizidine alkaloids with senecionine in it has been shown to be toxic to ''

Fusarium ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil mi ...

'' fungi at

millimolar Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...

concentrations.

Treatment

There are currently no known available

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

s or

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

s to treat senecionine poisoning. Treatment is supportive to permit

liver regeneration Liver regeneration is the process by which the liver is able to replace lost liver tissue. The liver is the only visceral organ with the capacity to regenerate. The liver can regenerate after partial surgical removal or chemical injury. As little ...

, which may include administration of intravenous (IV) fluids to correct

dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...

and

electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...

s, IV

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

, and

wound care The history of wound care spans from prehistory to modern medicine. Wounds naturally heal by themselves, but hunter-gatherers would have noticed several factors and certain herbal remedies would speed up or assist the process, especially if it was ...

with

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

s if dermatitis is a presenting symptom. Additionally,

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

infusions may be used to reduce ascites. Prevention remains the best method to reduce senecionine poisonings, including avoiding consumption of senecionine-containing plants and

pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...

use to kill infestations of those plants.

Biosynthesis and Chemistry

In ''

'' species, biosynthesis of senecionine starts from L-arginine or L-ornithine. Because plants don't have

decarboxylase Carboxy-lyases, also known as decarboxylases, are carbon–carbon lyases that add or remove a carboxyl group from organic compounds. These enzymes catalyze the decarboxylation of amino acids, beta-keto acids and alpha-keto acids. Classification ...

enzyme for L-ornithine, it must be first converted into L-arginine. Arginine can then be readily converted to

putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh, b ...

and

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen. Function Spermidine is an aliphatic polyamine. Spermidine synthase (SPDS) ...

. Next, in an

NAD+ Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...

-dependent reaction catalyzed by homospermidine synthase (HSS), an aminopropyl group from putrescine is transferred to spermidine to form homospermidine, releasing 1,3-diaminopropane (see biosynthesis scheme). HSS is the only enzyme that has been definitively implicated in this biosynthesis. Homospermidine is then oxidized and subsequently cyclized to form the

stereospecific In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one (or a subset) of the stereoisomers."Overlap Con ...

pyrrolizidine backbone. The

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

is then reduced and then the pyrrolizidine core is desaturated and hydroxylated through yet undetermined mechanisms to form retronecine. Retronecine is

acylated In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with ...

by senecic acid, formed from two equivalents of L-isoleucine. This step forms the ''N''-oxide of senecionine, which is subsequently reduced to yield senecionine. Senecionine has a core structure of retronecine, an unsaturated pyrrolizide, with a 12-membered

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

ring attached to the core. The

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

atom in the pyrrolizidine core is weakly basic with an estimated pKa of 5.9. Senecionine_biosynthesis5

Metabolism and Mechanism of Action

After oral ingestion, senecionine is absorbed from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

. When it reaches the

, it is metabolized via three pathways: ''N''-oxidation,

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

, and

ester hydrolysis In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are fa ...

. ''N-''oxidation and hydrolysis are detoxification pathways, and the products of these reactions are conjugated and excreted by the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s. However, the ''N-''oxide may be converted back into senecionine by

cytochrome P-450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

(CYP450) monooxygenases. Oxidation of senecionine to its respective dehydropyrrolizidine is responsible for its toxic effects. In the toxic pathway, the 2-pyrroline in the core is desaturated via an oxidation reaction to form a pyrrolic ester. This metabolite can still subsequently be eliminated if it is conjugated to glutathione. However, this metabolite is toxic because it can act as an

electrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries ...

. It may be attacked by either DNA

base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

or by

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

residues in liver proteins, resulting in the formation of toxic

adduct An adduct (from the Latin ''adductus'', "drawn toward" alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all co ...

s, including

cross-link In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...

ed adducts between DNA base pairs, liver proteins, or both. These adducts can damage DNA, leading to

genotoxicity Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic sub ...

and

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

, and liver enzymes and

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s, leading to

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

Biology and Society

African monarch (Danaus chrysippus orientis)

The ''Senecio'' plants

groundsel Groundsel is a common name for several plants and may refer to: *Members of the genus ''Senecio'' **Creeping groundsel, ''Senecio angulatus'' **Common groundsel, ''Senecio vulgaris'' **Welsh groundsel, '' Senecio cambrensis'' **York radiate grounds ...

and

ragwort ''Jacobaea vulgaris'', syn. ''Senecio jacobaea'', is a very common wild flower in the family Asteraceae that is native to northern Eurasia, usually in dry, open places, and has also been widely distributed as a weed elsewhere. Common names inc ...

are both common and are found in many regions, most commonly as weeds on cultivated ground. Common ragwort is especially prevalent in Europe and has been responsible for

livestock Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to animals ...

poisoning and deaths when it is consumed. In Africa, Australia, and the United States, ''Crotalaria'' species, shrub-like herbs, have been found to be responsible for similar livestock deaths. Horses seem to be particularly vulnerable to senecionine poisoning through ingestion of ragwort. Symptoms of poisoning in horses (known as "horse staggers") include nervousness, yawning, fatigue, and unsteady gait. Some species have evolved to leverage senecionine for their own benefit. ''

Danaus chrysippus ''Danaus chrysippus'', also known as the plain tiger, African queen, or African monarch, is a medium-sized butterfly widespread in Asia, Australia and Africa. It belongs to the Danainae subfamily of the brush-footed butterfly family Nymphalidae. ...

'' butterflies can safely consume senecionine-containing plants, making them taste very bitter and thus unpalatable to predators. This adaptation is also present in grasshoppers of the genus '' Zonocerus'' and the

caterpillar Caterpillars ( ) are the larval stage of members of the order Lepidoptera (the insect order comprising butterflies and moths). As with most common names, the application of the word is arbitrary, since the larvae of sawflies (suborder Sym ...

s of the

Cinnabar moth The cinnabar moth (''Tyria jacobaeae'') is a brightly coloured arctiid moth found as a native species in Europe and western and central Asia then east across the Palearctic to Siberia to China. It has been introduced into New Zealand, Australia a ...

. Additionally, ''D. chrysippus'' are able to convert senecionine to

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

s necessary for successful

mating In biology, mating is the pairing of either opposite-sex or hermaphroditic organisms for the purposes of sexual reproduction. ''Fertilization'' is the fusion of two gametes. ''Copulation'' is the union of the sex organs of two sexually reproduc ...

. Consequently, experiments have shown that males deprived of pyrrolizidine alkaloids, including senecionine, in their diets are less successful at mating. Senecionine-containing herbs have been used in

folk medicine Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...

for the treatment of

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, and as a

uterine The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the hollow organ, organ in the female reproductive system, reproductive system of most female mammals, including humans that accommodates the embryonic development, embryonic an ...

stimulant, despite no documented evidence that it is effective for any of those conditions and overwhelming evidence of its toxicity.{{cite book , editor-last1=Blumenthal , editor-first1=M , title=The complete German Commission E monographs, Therapeutic guide to herbal medicines , year=1998 , publisher=American Botanical Council , isbn=096555550X , page=376 In humans, bread contaminated with ragwort has caused senecionine poisonings (a condition colloquially known as "bread poisoning" in

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...

). In the

West Indies The West Indies is a subregion of North America, surrounded by the North Atlantic Ocean and the Caribbean Sea that includes 13 independent island countries and 18 dependencies and other territories in three major archipelagos: the Greater A ...

, poisonings have been reported from the consumption of

herbal tea Herbal teas, also known as herbal infusions and less commonly called tisanes (UK and US , US also ), are beverages made from the infusion or decoction of herbs, spices, or other plant material in hot water. Oftentimes herb tea, or the plain term ...

s made with ''Crotalaria''.

References

Tertiary alcohols Pyrrolizidine alkaloids Lactones Alkene derivatives Plant toxins Heterocyclic compounds with 3 rings

Toxicity

Liver toxicity

DNA damage

Diagnosis

Other Bioactivity

Treatment

Biosynthesis and Chemistry

Metabolism and Mechanism of Action

Biology and Society

See also

References