Anti-inflammatory
Encyclopedia
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation
. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system
.
s, to be specific glucocorticoid
s, reduce inflammation or swelling by binding to glucocorticoid receptors
. These drugs are often referred to as corticosteroid
s.
s (NSAIDs), alleviate pain by counteracting the cyclooxygenase
(COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the pain.
Some common examples of NSAIDs are: aspirin
, ibuprofen
, and naproxen
. The newer specific COX-inhibitors - although, it is presumed, sharing a similar mode of action - are not classified together with the traditional NSAIDs.
On the other hand, there are analgesic
s that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is paracetamol
, called acetaminophen in the U.S. and sold under the brand name of Tylenol
. As opposed to NSAIDS, which reduce pain and inflammation by inhibiting COX enzymes, paracetamol has recently been shown to block the reuptake of endocannabinoids, which only reduces pain, likely explaining why it has minimal effect on inflammation.
Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk increases almost twentyfold for those over 75. Other dangers of NSAIDs are exacerbating asthma and causing kidney damage.
are a class of peptides being developed by IMULAN BioTherapeutics, LLC
, which were discovered to have diverse biological properties, including anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory
cells, which are immune cells responsible for amplifying the inflammatory response. The ImSAIDs represent a new category of anti-inflammatory and are unrelated to steroid
hormones or non-steroidal anti-inflammatories.
The ImSAIDs were discovered by scientists evaluating biological properties of the submandibular gland
and saliva
. Early work in this area demonstrated that the submandibular gland released a host of factors that regulate systemic inflammatory responses and modulate systemic immune and inflammatory reactions. It is now well accepted that the immune, nervous, and endocrine systems communicate and interact to control and modulate inflammation
and tissue
repair. One of the neuroendocrine pathways, when activated, results in the release of immune-regulating peptides from the submandibular gland upon neuronal stimulation from sympathetic
nerves. This pathway or communication is referred to as the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the systemic control of inflammation.
Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acid
peptide
, called the submandibular gland peptide-T. SGP-T was demonstrated to have biological activity and thermoregulatory properties related to endotoxin
exposure. SGP-T, an isolate of the submandibular gland, demonstrated its immunoregulatory properties and potential role in modulating the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently was shown to play an important role in the control of inflammation.
One SGP-T derivative is a three-amino acid sequence shown to be a potent anti-inflammatory molecule
with systemic effects. This three-amino acid peptide is phenylalanine
-glutamine
-glycine
(FEG) and its D-isomer
ic form (feG) have become the foundation for the ImSAID category. Cellular Effects of feG: The cellular effects of the ImSAIDs are characterized in a number of publications. feG and related peptides are known to modulate leukocyte (white blood cells) activity by influencing cell surface receptors to inhibit excessive activation and tissue infiltration.
One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known to alter leukocyte adhesion involving actions on αMβ2 integrin
, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils. feG has also been shown to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular oxidative activity, and reduce the expression of CD49d after antigen exposure.
s may have anti-inflammatory qualities, including Harpagophytum
, hyssop
, ginger
, Turmeric
, Arnica montana
, which contains helenalin
, a sesquiterpene lactone
, and willow bark
, which contains salicylic acid
, the active ingredient in aspirin. Cannabichromene, one of the many cannabinoids present in the cannabis
plant, has been shown to reduce inflammation.
. By contrast, anti-inflammatory treatment trials for existing Alzheimer's disease
have typically shown little to no effect on halting or reversing the disorder. Research and clinical trials continue.
, or even cool water, to a tissue injury has an anti-inflammatory effect and is often suggested as an injury treatment and pain management
technique for athletes. One common approach is Rest, Ice, Compression and Elevation
. Cool temperatures inhibit local blood circulation, which reduces swelling in the injured tissue.
(which contain higher levels of omega-3 fatty acid
s), nuts, seeds, and certain spices, such as ginger
. Extra-virgin olive oil
contains the chemical oleocanthal
that acts similarly to ibuprofen. Those following an anti-inflammatory diet will avoid refined oils and sugars, and show a preference for so-called anti-inflammatory foods in their meal choices.
A diet high in vegetables and low in refined carbohydrates and saturated and trans fats may enhance the creation of prostaglandins. There are three main types of prostaglandins: PG-E1 and PG-E3, which have an anti-inflammatory properties, and PG-E2, which promotes inflammation.
Omega-3 fatty acids have been shown to disrupt inflammation cell signaling
pathways by binding to the GPR120
receptor.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
Steroids
Many steroidSteroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s, to be specific glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s, reduce inflammation or swelling by binding to glucocorticoid receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
. These drugs are often referred to as corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugNon-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s (NSAIDs), alleviate pain by counteracting the cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the pain.
Some common examples of NSAIDs are: aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, and naproxen
Naproxen
Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
. The newer specific COX-inhibitors - although, it is presumed, sharing a similar mode of action - are not classified together with the traditional NSAIDs.
On the other hand, there are analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
, called acetaminophen in the U.S. and sold under the brand name of Tylenol
Tylenol
Tylenol is a North American brand of drugs advertised for reducing pain, reducing fever, and relieving the symptoms of allergies, cold, cough, and flu. The active ingredient of its original, flagship product, paracetamol , is marketed as an analgesic and antipyretic...
. As opposed to NSAIDS, which reduce pain and inflammation by inhibiting COX enzymes, paracetamol has recently been shown to block the reuptake of endocannabinoids, which only reduces pain, likely explaining why it has minimal effect on inflammation.
Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk increases almost twentyfold for those over 75. Other dangers of NSAIDs are exacerbating asthma and causing kidney damage.
Immune Selective Anti-Inflammatory Derivatives (ImSAIDs)
ImSAIDsImmune-selective anti-inflammatory derivative
Immune Selective Anti-Inflammatory Derivatives are a class of peptides being developed by IMULAN BioTherapeutics, LLC, which were discovered to have diverse biological properties, including anti-inflammatory properties...
are a class of peptides being developed by IMULAN BioTherapeutics, LLC
IMULAN BioTherapeutics, LLC
-About:IMULAN BioTherapeutics, LLC, is a veterinary immunobiology company developing a range of immune based therapies for veterinary medicine. IMULAN BioTherapeutics, LLC has several divisions related to immuno-biology and comparative medicine....
, which were discovered to have diverse biological properties, including anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
cells, which are immune cells responsible for amplifying the inflammatory response. The ImSAIDs represent a new category of anti-inflammatory and are unrelated to steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
hormones or non-steroidal anti-inflammatories.
The ImSAIDs were discovered by scientists evaluating biological properties of the submandibular gland
Submandibular gland
The paired submandibular glands are salivary glands located beneath the floor of the mouth. In humans, they account for 70% of the salivary volume and weigh about 15 grams. Unstimulated in humans, the percentage contribution to whole saliva; ~25% Parotid, Submandibular and Sublingual ~ 67% and...
and saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
. Early work in this area demonstrated that the submandibular gland released a host of factors that regulate systemic inflammatory responses and modulate systemic immune and inflammatory reactions. It is now well accepted that the immune, nervous, and endocrine systems communicate and interact to control and modulate inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
repair. One of the neuroendocrine pathways, when activated, results in the release of immune-regulating peptides from the submandibular gland upon neuronal stimulation from sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
nerves. This pathway or communication is referred to as the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the systemic control of inflammation.
Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
, called the submandibular gland peptide-T. SGP-T was demonstrated to have biological activity and thermoregulatory properties related to endotoxin
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...
exposure. SGP-T, an isolate of the submandibular gland, demonstrated its immunoregulatory properties and potential role in modulating the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently was shown to play an important role in the control of inflammation.
One SGP-T derivative is a three-amino acid sequence shown to be a potent anti-inflammatory molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
with systemic effects. This three-amino acid peptide is phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
-glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
-glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
(FEG) and its D-isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
ic form (feG) have become the foundation for the ImSAID category. Cellular Effects of feG: The cellular effects of the ImSAIDs are characterized in a number of publications. feG and related peptides are known to modulate leukocyte (white blood cells) activity by influencing cell surface receptors to inhibit excessive activation and tissue infiltration.
One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known to alter leukocyte adhesion involving actions on αMβ2 integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils. feG has also been shown to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular oxidative activity, and reduce the expression of CD49d after antigen exposure.
Herbs
In addition to medical drugs, some herbHerb
Except in botanical usage, an herb is "any plant with leaves, seeds, or flowers used for flavoring, food, medicine, or perfume" or "a part of such a plant as used in cooking"...
s may have anti-inflammatory qualities, including Harpagophytum
Harpagophytum
Harpagophytum procumbens, also called grapple plant, wood spider and most commonly devil's claw, is a plant of the sesame family, native to South Africa. It got its name from the peculiar appearance of its hooked fruit. The plant's large tuberous roots are used medicinally to reduce pain and fever,...
, hyssop
Hyssop
Hyssop is a genus of about 10-12 species of herbaceous or semi-woody plants in the family Lamiaceae, native from the east Mediterranean to central Asia. They are aromatic, with erect branched stems up to 60 cm long covered with fine hairs at the tips. The leaves are narrow oblong, 2–5 cm...
, ginger
Ginger
Ginger is the rhizome of the plant Zingiber officinale, consumed as a delicacy, medicine, or spice. It lends its name to its genus and family . Other notable members of this plant family are turmeric, cardamom, and galangal....
, Turmeric
Turmeric
Turmeric is a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae. It is native to tropical South Asia and needs temperatures between 20 °C and 30 °C and a considerable amount of annual rainfall to thrive...
, Arnica montana
Arnica montana
Arnica montana, known commonly as leopard's bane, wolf's bane, mountain tobacco and mountain arnica, is a European flowering plant with large yellow capitula....
, which contains helenalin
Helenalin
Helenalin is a sesquiterpene lactone with potent anti-inflammatory and antitumor effects found in Arnica montana and Arnica chamissonis foliosa...
, a sesquiterpene lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
, and willow bark
Willow
Willows, sallows, and osiers form the genus Salix, around 400 species of deciduous trees and shrubs, found primarily on moist soils in cold and temperate regions of the Northern Hemisphere...
, which contains salicylic acid
Salicylic acid
Salicylic acid is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin...
, the active ingredient in aspirin. Cannabichromene, one of the many cannabinoids present in the cannabis
Cannabis
Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...
plant, has been shown to reduce inflammation.
Possible benefits
Some clinical studies have suggested that a prolonged intake of certain anti-inflammatory (non-steroid) drugs may have a positive effect on Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. By contrast, anti-inflammatory treatment trials for existing Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
have typically shown little to no effect on halting or reversing the disorder. Research and clinical trials continue.
Ice treatment
Applying iceIce
Ice is water frozen into the solid state. Usually ice is the phase known as ice Ih, which is the most abundant of the varying solid phases on the Earth's surface. It can appear transparent or opaque bluish-white color, depending on the presence of impurities or air inclusions...
, or even cool water, to a tissue injury has an anti-inflammatory effect and is often suggested as an injury treatment and pain management
Pain management
Pain management is a branch of medicine employing an interdisciplinary approach for easing the suffering and improving the quality of life of those living with pain. The typical pain management team includes medical practitioners, clinical psychologists, physiotherapists, occupational therapists,...
technique for athletes. One common approach is Rest, Ice, Compression and Elevation
RICE (medicine)
RICE is a treatment method for soft tissue injury which is an acronym for Rest, Ice, Compression and Elevation. When used appropriately, recovery duration is usually shortened and discomfort minimized....
. Cool temperatures inhibit local blood circulation, which reduces swelling in the injured tissue.
Food
Some advocate the consumption of anti-inflammatory foods as a means of controlling inflammation. A typical anti-inflammatory diet includes a well-balanced, varied diet that is high in vegetables and low in refined carbohydrates and fats, such as saturated fats and trans fats. Anti-inflammatory foods include most colorful fruits and vegetables, oily fishOily fish
Oily fish have oil in their tissues and in the belly cavity around the gut. Their fillets contain up to 30 percent oil, although this figure varies both within and between species...
(which contain higher levels of omega-3 fatty acid
Omega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
s), nuts, seeds, and certain spices, such as ginger
Ginger
Ginger is the rhizome of the plant Zingiber officinale, consumed as a delicacy, medicine, or spice. It lends its name to its genus and family . Other notable members of this plant family are turmeric, cardamom, and galangal....
. Extra-virgin olive oil
Olive oil
Olive oil is an oil obtained from the olive , a traditional tree crop of the Mediterranean Basin. It is commonly used in cooking, cosmetics, pharmaceuticals, and soaps and as a fuel for traditional oil lamps...
contains the chemical oleocanthal
Oleocanthal
Oleocanthal is a natural organic compound isolated from extra virgin olive oil. It is responsible for the slightly peppery "bite" of extra virgin olive oil. Oleocanthal is a tyrosol ester and its chemical structure is related to oleuropein that is also found in olive oil.Oleocanthal has been found...
that acts similarly to ibuprofen. Those following an anti-inflammatory diet will avoid refined oils and sugars, and show a preference for so-called anti-inflammatory foods in their meal choices.
A diet high in vegetables and low in refined carbohydrates and saturated and trans fats may enhance the creation of prostaglandins. There are three main types of prostaglandins: PG-E1 and PG-E3, which have an anti-inflammatory properties, and PG-E2, which promotes inflammation.
Omega-3 fatty acids have been shown to disrupt inflammation cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
pathways by binding to the GPR120
GPR120
G-protein coupled receptor 120 is a protein that in humans is encoded by the GPR120 gene.GPR120 has also been shown to mediate the anti-inflammatory and insulin-sensitizing effects of omega 3 fatty acids.-Further reading:...
receptor.