Arachidonate 5-lipoxygenase inhibitor

Edit links
Source: Wikipedia, the free encyclopedia.

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.[1][2]

Examples of 5-LOX inhibitors include the pharmaceutical drugs

meclofenamate sodium, zileuton[3][4] and the natural products myxochelins/pseudochelin[5][6] as well as nordihydroguaiaretic acid (NDGA).[7]

Some chemicals found in trace amounts in food, as well as some dietary supplements, have been shown to inhibit 5-LOX; these include

St John's wort.[8][9][10]

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.[7] Boswellia administration has been shown to reduce brain edema in patients irradiated for brain tumor and it's believed to be due to 5-lipoxygenase inhibition.[11][12]

See also

References

  1. ^ David L. Nelson, Michael M. Cox. Lehninger's Principles of Biochemistry, Fifth Edition. W.H. Freeman and Co., 2008, p. 359.
  2. S2CID 1103848
    .
  3. ^
    PMID 23752617
    .
  4. ^ "Zyflo (Zileuton tablets)" (PDF). United States Food and Drug Administration. Cornerstone Therapeutics Inc. June 2012. p. 1. Retrieved 12 December 2014. Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both the (R)-(+)- and (S)-(-)-enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients.
  5. PMID 25686392
    .
  6. S2CID 201675694
    .
  7. ^
    PMID 32393899
    .
  8. PMID 12018529
    .
    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
  9. PMID 24976853
    . These researches are according to an investigation of the effect of H. perforatum on the NF-κB inflammation factor, conducted by Bork et al. (1999), in which hyperforin provided a potent inhibition of TNFα-induced activation of NF-κB [58]. Another important activity for hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase [59]. Moreover, this species attenuated the expression of iNOS in periodontal tissue, which may contribute to the attenuation of the formation of nitrotyrosine, an indication of nitrosative stress [26]. In this context, a combination of several active constituents of Hypericum species is the carrier of their anti-inflammatory activity.
  10. PMID 24214835
    . Anti-inflammatory mechanisms of hyperforin have been described as inhibition of cyclooxygenase-1 (but not COX-2) and 5-lipoxygenase at low concentrations of 0.3 μmol/L and 1.2 μmol/L, respectively [52], and of PGE2 production in vitro [53] and in vivo with superior efficiency (ED50 = 1 mg/kg) compared to indomethacin (5 mg/kg) [54]. Hyperforin turned out to be a novel type of 5-lipoxygenase inhibitor with high effectivity in vivo [55] and suppressed oxidative bursts in polymorphonuclear cells at 1.8 μmol/L in vitro [56]. Inhibition of IFN-γ production, strong downregulation of CXCR3 expression on activated T cells, and downregulation of matrix metalloproteinase 9 expression caused Cabrelle et al. [57] to test the effectivity of hyperforin in a rat model of experimental allergic encephalomyelitis (EAE). Hyperforin attenuated the symptoms significantly, and the authors discussed hyperforin as a putative therapeutic molecule for the treatment of autoimmune inflammatory diseases sustained by Th1 cells.
  11. ^ Simon Kirste (2009). Antiödematöse Wirkung von Boswellia serrata auf dasStrahlentherapie - assoziierte Hirnödem (MD thesis). Albert-Ludwigs-Universität Freiburg im Breisgau – via Deutsche National Bibliothek.
  12. PMID 21287538
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Arachidonate_5-lipoxygenase_inhibitor&oldid=1173883972"