Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the
arachidonate 5-lipoxygenase
Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...
(5-lipoxygenase or 5-LOX) enzyme, which is responsible for the production of inflammatory
leukotriene
Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...
s. The overproduction of leukotrienes is a major cause of inflammation in
asthma
Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
, allergic
rhinitis
Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.
The inflammation is caused by viruses, bacteria, irritant ...
, and
osteoarthritis
Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...
.
Examples of 5-LOX inhibitors include the pharmaceutical drugs
meclofenamate sodium
Meclofenamic acid (used as meclofenamate sodium, brand name Meclomen) is a drug used for joint, muscular pain, arthritis and dysmenorrhea.
It is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory d ...
,
zileuton
Zileuton (trade name Zyflo) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laborato ...
and the natural products myxochelins/pseudochelin
as well as
nordihydroguaiaretic acid
Nordihydroguaiaretic acid (NDGA) is a classic lignan, a phenylpropane dimer linked by a bond between positions C8 and C8′, as opposed to a neolignan. It is a natural compound found in the creosote bush (''Larrea tridentata'').
Medical properti ...
(NDGA).
Some chemicals found in trace amounts in food, as well as some dietary supplements, have been shown to inhibit 5-LOX; these include
baicalein
Baicalein (5,6,7-trihydroxyflavone) is a flavone, a type of flavonoid, originally isolated from the roots of '' Scutellaria baicalensis'' and '' Scutellaria lateriflora''. It is also a constituent of '' Oroxylum indicum'' (Indian trumpetflower) ...
,
caffeic acid
Caffeic acid is an organic compound with the formula . It is a polyphenol with a key role in scavenging reactive oxygen species (ROS) generated in energy metabolism. Caffeic acid is also one major polyphenol responsible for maintaining normal le ...
,
curcumin
Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmetic ...
,
hyperforin
Hyperforin is a phytochemical produced by some of the members of the plant genus ''Hypericum'', notably ''Hypericum perforatum'' (St John's wort). Hyperforin may be involved in the pharmacology, pharmacological effects of St. John's wort, specifi ...
and
St John's wort.
[ ]
1. Arachidonate 5-lipoxygenase ...Specific function: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes ...
2. Prostaglandin G/H synthase 1 ... General function: Involved in peroxidase activity
Acetyl-keto-beta-boswellic acid (
AKBA), one of the bioactive boswellic acids found in Boswellia serrata (Indian Frankincense) has been found to inhibit 5-lipoxygenase strongly as an allosteric inhibitor.
Boswellia administration has been shown to reduce brain edema in patients irradiated for brain tumor and it is believed to be due to 5-lipoxygenase inhibition.
See also
*
Antileukotriene agents
*
Arachidonate 5-lipoxygenase ALOX5-inhibiting drugs
References
External links
*
*
Human Metabolome Database – Metabolites of 5-LOX
Oxidoreductase inhibitors
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