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Arachidonate 5-lipoxygenase Inhibitors
Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the arachidonate 5-lipoxygenase (5-lipoxygenase or 5-LOX) enzyme, which is responsible for the production of inflammatory leukotrienes. The overproduction of leukotrienes is a major cause of inflammation in asthma, allergic rhinitis, and osteoarthritis. Examples of 5-LOX inhibitors include the pharmaceutical drugs meclofenamate sodium, zileuton and the natural products myxochelins/pseudochelin as well as nordihydroguaiaretic acid (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, caffeic acid, curcumin, hyperforin 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 acti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 family of enzymes. It transforms essential fatty acids (EFA) substrates into leukotrienes as well as a wide range of other biologically active products. ALOX5 is a current target for pharmaceutical intervention in a number of diseases. Gene The ''ALOX5'' gene, which occupies 71.9 kilobase pairs (kb) on chromosome 10 (all other human lipoxygenases are clustered together on chromosome 17), is composed of 14 exons divided by 13 introns encoding the mature 78 kilodalton (kD) ALOX5 protein consisting of 673 amino acids. The gene promoter region of ALOX5 contains 8 GC boxes but lacks TATA boxes or CAT boxes and thus resembles the gene promoters of typical housekeeping genes. Five of the 8 GC boxes are arranged in tandem and are recognized by t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Leukotrienes
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes use lipid signaling to convey information to either the cell producing them (autocrine signaling) or neighboring cells (paracrine signaling) in order to regulate immune responses. The production of leukotrienes is usually accompanied by the production of histamine and prostaglandins, which also act as inflammatory mediators. One of their roles (specifically, leukotriene D4) is to trigger contractions in the smooth muscles lining the bronchioles; their overproduction is a major cause of inflammation in asthma and allergic rhinitis. Leukotriene antagonists are used to treat these disorders by inhibiting the production or activity of leukotrienes. History and name The name ''leukotriene'', introduced by Swedish biochemist Bengt Samuelss ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Asthma
Asthma is a 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 wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise. Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta blockers. Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate. It may also be classified as atopic or non-atopic, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, irritants or allergens. The most common kind of rhinitis is allergic rhinitis, which is usually triggered by airborne allergens such as pollen and dander. Allergic rhinitis may cause additional symptoms, such as sneezing and nasal itching, coughing, headache, fatigue, malaise, and cognitive impairment. The allergens may also affect the eyes, causing watery, reddened, or itchy eyes and puffiness around the eyes. The inflammation results in the generation of large amounts of mucus, commonly producing a runny nose, as well as a stuffy nose and post-nasal drip. In the case of allergic rhinitis, the inflammation is caused by the degranulation of mast cells in the nose. When mast cells degranulate, they release histamine and other chemicals, starting a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the world. The most common symptoms are joint pain and stiffness. Usually the symptoms progress slowly over years. Initially they may occur only after exercise but can become constant over time. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs; the knee and hip joints; and the joints of the neck and lower back. Joints on one side of the body are often more affected than those on the other. The symptoms can interfere with work and normal daily activities. Unlike some other types of arthritis, only the joints, not internal organs, are af ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 drugs (NSAIDs) and was approved by the US FDA in 1980. Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of prostaglandins. Scientists led by Claude Winder from Parke-Davis invented meclofenamate sodium in 1964, along with fellow members of the class, mefenamic acid in 1961 and flufenamic acid in 1963. Patents on the drug expired in 1985 and several generics were introduced in the US, but as of July 2015 only Mylan still sold it. It is not widely used in humans as it has a high rate (30-60%) rate of gastrointestinal side effects. Adverse effects In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 Laboratories and is now marketed in two formulations by Cornerstone Therapeutics Inc. under the brand names Zyflo and Zyflo CR. The original immediate-release formulation, Zyflo, is taken four times per day. The extended-release formulation, Zyflo CR, is taken twice daily. Although the 600 mg immediate release tablet (Zyflo) and extended release formulation of zileuton are still available (Zyflo CR), the 300 mg immediate release tablet was withdrawn from the U.S. market on February 12, 2008. Pharmacotherapy Indications and dosing Zileuton is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. Zileuton is not indicated for use in the reversal of bronchospasm in acute asthma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nordihydroguaiaretic Acid
Nordihydroguaiaretic acid, informally abbreviated NDGA in research articles, 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 properties As a lignan, it is a member of one of the major classes of phytoestrogens. While it is commonly asserted that the biological properties of lignans per sé are void, and that only the enterolignans enterodiol and enterolactone, produced from lignans by intestinal bacteria have interesting biological properties, nordihydroguaiaretic acid has antioxidant and anti-inflammatory properties in vitro or in animal models. It is a redox-type inhibitor of 5-lipoxygenase. A 1986 study involved feeding female mosquitos NDGA to test the effect on their average life span. While the usual mosquito life span was 29 days, the NDGA-fed mosquitos lived an average of 45 days—an increase of 50 percent. A 2008 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 reported in '' Oroxylum indicum'' (Indian trumpetflower) and ''Thyme''. It is the aglycone of baicalin. Baicalein is one of the active ingredients of Sho-Saiko-To, which is a Chinese classic herbal formula, and listed in Japan as Kampo medicine. As a Chinese herbal supplement, it is believed to enhance liver health. Baicalein, along with its analogue baicalin, is a positive allosteric modulator of the benzodiazepine site and/or a non-benzodiazepine site of the GABAA receptor. It displays subtype selectivity for α2 and α3 subunit-containing GABAA receptors. In accordance, baicalein shows anxiolytic effects in mice without incidence of sedation or myorelaxation. It is thought that baicalein, along with other flavonoids, may underlie the anxiolytic effects of ''S. baicalensis'' and ''S. late ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Caffeic Acid
Caffeic acid is an organic compound that is classified as a hydroxycinnamic acid. This yellow solid consists of both phenolic and acrylic functional groups. It is found in all plants because it is an intermediate in the biosynthesis of lignin, one of the principal components of woody plant biomass and its residues. Natural occurrences Caffeic acid can be found in the bark of ''Eucalyptus globulus'' the barley grain ''Hordeum vulgare'' and the herb ''Dipsacus asperoides''. It can also be found in the freshwater fern ''Salvinia molesta'' and in the mushroom ''Phellinus linteus''. Occurrences in food Free caffeic acid can be found in a variety of beverages, including brewed coffee at 0.13 mg per 100 ml and red wine at 2 mg per 100 ml. It is found at relatively high levels in herbs of the mint family, especially thyme, sage and spearmint (at about 20 mg per 100 g), and in spices, such as Ceylon cinnamon and star anise (at about 22 mg per 100 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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, cosmetics ingredient, food flavoring, and food coloring. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids, which are natural phenol, phenolic pigments responsible for the yellow color of turmeric. Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly bioavailable. It is unlikely to produce useful leads for drug development. History Curcumin was named in 1815 when Henri Auguste Vogel and Pierre Joseph Pelletier reported the first isolation of a "yellow coloring-matter" from the rhizomes of turmeric. Later, it was found to be a mixture of resin and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 pharmacological effects of St. John's wort, specifically in its antidepressant effects. Occurrence Hyperforin has only been found in significant amounts in ''Hypericum perforatum'' with other related species such as '' Hypericum calycinum'' containing lower levels of the phytochemical. It accumulates in oil glands, pistils, and fruits, probably as a plant defensive compound. The first natural extractions were done with ethanol and afforded a 7:1 yield of crude extract to phytochemical however, this technique produced a mixture of hyperforin and adhyperforin. The extraction technique has since been modernized using lipophilic liquid CO2 extraction to afford a 3:1 crude to phytochemical extraction which is then further purified away from adhyperforin. This CO2 extraction is rather tricky still because t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
