Allixin
Encyclopedia
Allixin is a phytoallexin found in garlic
(Allium sativum) bulbs. It was first isolated and characterized in 1989. When garlic is stored for long periods of time, it can form visible accumulations of crystalline allixin on its surface, particularly in areas where tissue has become necrotic
. After 2 years of storage, the amount of allixin accumulated can approach 1% of the dry weight of the cloves. Since allixin has weak antimicrobial
activity, these high concentrations are thought to be produced by the garlic bulb to protect itself from further damage from microorganisms.
Since allixin is found in high concentrations in garlic, there has been scientific interest in determining if it is responsible for any of the known health benefits of garlic. As a result of ongoing research, a variety of biological activities have been attributed to allixin. Pharmaceutical drug discovery
research based on derivatives of allixin has followed.
of allixin have been developed. In the first method, reported in 1997, allixin was synthesized in 22 steps starting from D-mannose
. A shorter synthesis was developed in 1998 which involved only 5 steps, starting from 5-methylfurfural.
studies, allixin demonstrates neurotrophic activity, but at high concentrations it has cytotoxic effects. Simple chemical analogs of allixin were found to have more potent neurotrophic activity, but without the cytotoxic effects. Allixin may therefore be a useful starting point for the development of pharmaceutical drugs for the treatment of neurodegenerative disorders or for neuronal regeneration in the brain.
Pharmacological studies have demonstrated that allixin exerts an anti-promoting activity against skin tumors induced by the chemical 12-O-tetradecanoylphorbol-13-acetate
(TPA) and an inhibitory effect on aflatoxin B1-induced mutagenesis
. Allixin may therefore be responsible, at least in part, for the tumor-preventative effects of garlic extract.
Allixin has also been shown to have a radical
scavenging
effect.
, bis(allixinato)oxovanadium(IV), is a potent anti-diabetic agent. In studies in streptozotocin
-induced diabetic mice, this vanadium complex was shown to be an insulin mimetic with hypoglycemic effects. Similarly, a zinc
-allixin complex, bis(allixinato)zinc(II), shows the same insulin mimetic effects. The mechanism of action
by which these complexes regulate insulin signaling pathways is unclear.
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
(Allium sativum) bulbs. It was first isolated and characterized in 1989. When garlic is stored for long periods of time, it can form visible accumulations of crystalline allixin on its surface, particularly in areas where tissue has become necrotic
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. After 2 years of storage, the amount of allixin accumulated can approach 1% of the dry weight of the cloves. Since allixin has weak antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
activity, these high concentrations are thought to be produced by the garlic bulb to protect itself from further damage from microorganisms.
Since allixin is found in high concentrations in garlic, there has been scientific interest in determining if it is responsible for any of the known health benefits of garlic. As a result of ongoing research, a variety of biological activities have been attributed to allixin. Pharmaceutical drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
research based on derivatives of allixin has followed.
Laboratory synthesis
Two laboratory synthesesOrganic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of allixin have been developed. In the first method, reported in 1997, allixin was synthesized in 22 steps starting from D-mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
. A shorter synthesis was developed in 1998 which involved only 5 steps, starting from 5-methylfurfural.
Biological activities
In in vitroIn vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies, allixin demonstrates neurotrophic activity, but at high concentrations it has cytotoxic effects. Simple chemical analogs of allixin were found to have more potent neurotrophic activity, but without the cytotoxic effects. Allixin may therefore be a useful starting point for the development of pharmaceutical drugs for the treatment of neurodegenerative disorders or for neuronal regeneration in the brain.
Pharmacological studies have demonstrated that allixin exerts an anti-promoting activity against skin tumors induced by the chemical 12-O-tetradecanoylphorbol-13-acetate
12-O-Tetradecanoylphorbol-13-acetate
12-O-tetradecanoylphorbol-13-acetate , also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate , is diester of phorbol and a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein...
(TPA) and an inhibitory effect on aflatoxin B1-induced mutagenesis
Mutagenesis
Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...
. Allixin may therefore be responsible, at least in part, for the tumor-preventative effects of garlic extract.
Allixin has also been shown to have a radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
scavenging
Scavenger (chemistry)
A scavenger in chemistry is a chemical substance added to a mixture in order to remove or inactivate impurities or unwanted reaction products. Their use is wide-ranged:...
effect.
Metal complexes
Metal complexes with allixin have been shown to have beneficial pharmacological effects in animal models of diabetes. A complex with vanadiumVanadium
Vanadium is a chemical element with the symbol V and atomic number 23. It is a hard, silvery gray, ductile and malleable transition metal. The formation of an oxide layer stabilizes the metal against oxidation. The element is found only in chemically combined form in nature...
, bis(allixinato)oxovanadium(IV), is a potent anti-diabetic agent. In studies in streptozotocin
Streptozotocin
Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals...
-induced diabetic mice, this vanadium complex was shown to be an insulin mimetic with hypoglycemic effects. Similarly, a zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
-allixin complex, bis(allixinato)zinc(II), shows the same insulin mimetic effects. The mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
by which these complexes regulate insulin signaling pathways is unclear.