Leonurine (also known as SCM-198 in research) is a pseudoalkaloid that has been isolated from ''

Leonotis leonurus ''Leonotis leonurus'', also known as lion's tail and wild dagga, is a plant species in the mint family, Lamiaceae. The plant is a broadleaf evergreen large shrub native to South Africa, where it is very common.

'', ''

Leonotis nepetifolia ''Leonotis nepetifolia'', (also known as klip dagga, Christmas candlestick, or lion's ear), is a species of plant in the genus ''Leonotis'' and the family Lamiaceae (mint), It is native to tropical Africa. It can also be found growing abundantly ...

'', ''

Leonurus japonicus ''Leonurus japonicus'', commonly called oriental motherwort or Chinese motherwort, is a herbaceous flowering plant native to Asia, including Korea and Japan, and China to Cambodia. Description Plants are annual or biennial, growing from taproots ...

'', ''

Leonurus cardiaca ''Leonurus cardiaca'', known as motherwort, is an herbaceous perennial plant in the mint family, Lamiaceae. Other common names include throw-wort, lion's ear, and lion's tail. Lion's tail is also a common name for ''Leonotis leonurus'', and lion' ...

'' (motherwort), ''

Leonurus sibiricus ''Leonurus sibiricus'', commonly called honeyweed or Siberian motherwort, is an herbaceous plant species native to China, Mongolia, and Siberia. It has verticillaster inflorescence. It is naturalized in many other parts of the world, including S ...

'', as well as other plants of family

Lamiaceae The Lamiaceae ( ) or Labiatae are a family (biology), family of flowering plants commonly known as the mint, deadnettle, or sage family. Many of the plants are aromatic in all parts and include widely used culinary herbs like basil (herb), ba ...

. Leonurine is easily extracted into water.

Research

Leonurine weakly binds to multiple

GABA receptor The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and ...

sites including the GABA_A receptor. However, it shows much higher affinity as a 5-HT3A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" (from ...

, and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

in chronic mild stress studies on mice and inhibits the production of pro-inflammatory

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s. Leonurine has been investigated as a potential treatment for cardiovascular disorders. It protects against oxidative damage from ischemic stroke and demonstrates neuroprotective activity against focal cerebral ischemia brain injury induced on rats. Leonurine protects mice from pneumonia induced by influenza A. Leonurine has demonstrated anti-cancer activity ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and in animal studies.

Metabolites

Metabolites of leonurine in rats dosed orally include leonurine-10-O-sulfate (the sulfate conjugate of leonurine), leonurine-10-''O''-β-D-glucuronide (the

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

metabolite of leonurine) and an ''O''-demethylated leonurine analog that has not yet had its structure definitively confirmed.

Chemical synthesis

Leonurine can be synthesized starting from

eudesmic acid Eudesmic acid is an ''O''-methylated trihydroxybenzoic acid. Natural Occurrence It can be found in '' Eucalyptus spp.'' Synthesis Eudesmic acid is most directly synthesized by reaction of gallic acid with dimethyl sulfate. Derivatives #Esteri ...

. Reaction with sulfuric acid produces

syringic acid Syringic acid is a naturally occurring phenolic compound and dimethoxybenzene that is commonly found as a plant metabolite. Natural occurrence Syringic acid can be found in several plants including '' Ardisia elliptica'' and ''Schumannianthus ...

Protection Protection is any measure taken to guard something against damage caused by outside forces. Protection can be provided to physical objects, including organisms, to systems, and to intangible things like civil and political rights. Although ...

with

ethyl chloroformate Ethyl chloroformate is an organic compound with the chemical formula . It is the ethyl ester of chloroformic acid. It is a colorless, corrosive and highly toxic liquid. It is a reagent used in organic synthesis for the introduction of the ethyl c ...

followed by reaction with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately Volatility (chemistry), volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a Halogenation, chlorinating reagen ...

(SOCl₂) and then

tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...

yields 4-carboethoxysyringic acid 4-chloro-1-butyl ester. The chloride is then converted to an

amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

via a

Gabriel synthesis The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel. The Gabriel reacti ...

(with

potassium phthalimide Potassium phthalimide is a chemical compound of formula C8H4KNO2. It is the potassium salt of phthalimide, and usually presents as fluffy, very pale yellow crystals. It can be prepared by adding a hot solution of phthalimide in ethanol to a solutio ...

) followed by hydrazinolysis (

Ing–Manske procedure The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel. The Gabriel reaction ...

). The final step is reaction of the amine with ''S''-methylisothiourea hemisulfate salt. : Leonurinesynthesis

Research

Metabolites

Chemical synthesis

References

Further reading