Crocetin is a natural apocarotenoid

dicarboxylic acid In organic chemistry, a dicarboxylic acid is an organic compound containing two carboxyl groups (). The general molecular formula for dicarboxylic acids can be written as , where R can be aliphatic or aromatic. In general, dicarboxylic acids show ...

that is found in the crocus flower together with its glycoside,

crocin Crocin is a carotenoid chemical compound that is found in the flowers of crocus and gardenia. Crocin is the chemical primarily responsible for the color of saffron. Chemically, crocin is the diester formed from the disaccharide gentiobiose and ...

, and ''

Gardenia jasminoides ''Gardenia jasminoides'', commonly known as gardenia, is an evergreen flowering plant in the coffee family Rubiaceae. It is native to parts of South-East Asia. Wild plants range from 30 centimetres to 3 metres (about 1 to 10 feet) in height. The ...

'' fruits. It forms brick red crystals with a melting point of 285°C. The chemical structure of crocetin forms the central core of

, the compound responsible for the color of saffron.

Cell studies

Crocin and crocetin may provide neuroprotection in rats by reducing the production of various neurotoxic molecules, based on an in-vitro cell study.

Physiological effects

A 2009 study involving 14 individuals indicated that oral administration of crocetin may decrease the effects of physical fatigue in healthy men. A 2010 pilot study investigated the effect of crocetin on sleep. The clinical trial comprised a double-blind, placebo-controlled, crossover trial of 21 healthy adult men with a mild sleep complaint. It concluded that crocetin may (p=0.025) contribute to improving the quality of sleep. In high concentrations, it has protective effects against retinal damage '' in vitro'' and '' in vivo''.

Transcrocetinate sodium

The sodium salt of crocetin, transcrocetinate sodium ( INN, also known as trans sodium crocetinate or TSC) is an experimental drug that increases the movement of oxygen from

red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

into hypoxic (oxygen-starved) tissues. Transcrocetinate sodium belongs to a group of substances known as bipolar trans carotenoid salts, which constitute a subclass of oxygen diffusion-enhancing compounds. Transcrocetinate sodium was one of the first such compounds discovered.

Transcrocetinate sodium can be prepared by reacting saffron with

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

and extracting the salt of the trans crocetin

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

from the solution. John L. Gainer and colleagues have investigated the effects of transcrocetinate sodium in animal models. They discovered that the drug could reverse the potentially fatal decrease in blood pressure produced by the loss of large volumes of blood in severe hemorrhage, and thereby improve survival. Early investigations of transcrocetinate sodium suggested that it had potential applications in battlefield medicine, specifically in treatment of the many combat casualties with hemorrhagic shock. Additional studies, carried out in animal models and in clinical trials in humans, indicated that transcrocetinate sodium might prove beneficial in the treatment of a variety of conditions associated with

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

and

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

(a lack of oxygen reaching the tissues, usually due to a disruption in the circulatory system), including cancer, myocardial infarction (heart attack), and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. Transcrocetinate sodium has shown promise of effectiveness in restoring tissue oxygen levels and improving the ability to walk in a clinical trial of patients with peripheral artery disease (PAD) in which reduced delivery of oxygen-rich blood to tissues can cause severe leg pain and impair mobility. The drug has also been under investigation in a clinical trial sponsored by drug developer

Diffusion Pharmaceuticals Diffusion Pharmaceuticals Inc (NASDAQ:DFFN) is a publicly traded biotechnology and drug development company based in Charlottesville, Virginia, U.S. It was co-founded in 2001 by American life sciences entrepreneur David Kalergis and University o ...

for potential use as a

radiosensitizer A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer. Mechanism of action Conventional chemotherapeutics are currently being used in con ...

, increasing the susceptibility of hypoxic cancer cells to radiation therapy, in patients with a form of brain cancer known as glioblastoma. The drug is currently under investigation for its possible use in enhancing the oxygenation status of COVID-19 patients at risk for developing multiple organ failure due to severe respiratory distress.

Mechanism of action

Similar to other oxygen diffusion-enhancing compounds, transcrocetinate sodium appears to improve oxygenation in hypoxic tissues by exerting hydrophobic effects on water molecules in blood plasma and thereby increasing the hydrogen bonding between the water molecules. This in turn causes the overall organization of water molecules in plasma to become more structured, which facilitates the diffusion of oxygen through plasma and promotes the movement of oxygen into tissues. Trans-crocetin has been found to act as an NMDA receptor antagonist with high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

, and has been implicated in the

psychoactivity A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...

of saffron.

References

{{Ionotropic glutamate receptor modulators Apocarotenoids Dicarboxylic acids NMDA receptor antagonists Saffron

Cell studies

Physiological effects

Transcrocetinate sodium

Mechanism of action

See also

References