아라키돈산 5리포크시겐아제 억제제

Arachidonate 5-lipoxygenase inhibitor

아라키돈산 5-립포크시제나제 억제제는 염증성 백혈구아제 생성을 담당하는 아라키돈산 5-립포크시제나 5-LOX) 효소의 작용을 늦추거나 멈추게 하는 화합물이다.백혈구 과잉생산은 천식, 알레르기 비염, 골관절염 등에 염증이 생기는 주요 원인이다.[1][2]

5-LOX 억제제의 예로는 약제 메클로페나메이트 나트륨,[3] 질류톤[3][4], 천연물 myxochelins/pseudochlin[5][6] 및 NDGA(nordihydroguaareic acid, NDGA) 등이 있다.[7]

식품에서 미량에서 발견되는 일부 화학 물질과 일부 식이 보조식품은 5-LOX를 억제하는 것으로 나타났다; 이것들은 바이칼레인,[3] 카페인산,[3] 쿠르쿠민,[3] 하이퍼포린[8][9][10], 그리고 세인트 존의 wort를 포함한다.[8][9][10]

보즈웰리아 세라타(인도 프랑킨센스)에서 발견된 생체활성 보웰산 중 하나인 아세틸-케토-베타-보스웰릭산(AKBA)이 알로스테리 억제제로서 5리폭시제네제를 강하게 억제하는 것으로 밝혀졌다.[7]보스웰리아 투여는 뇌종양에 대해 조사된 환자의 뇌 부종을 감소시키는 것으로 나타났으며 이는 5-Lipoxygenase 억제 때문인 것으로 추정된다.[11][12]

참고 항목

참조

  1. ^ 데이비드 L.넬슨, 마이클 M. 콕스 레닝거의 생화학 원리 제5판W.H. Freeman and Co., 2008, 페이지 359.
  2. ^ Laufer, S (2003). "Role of eicosanoids in structural degradation in osteoarthritis". Curr Opin Rheumatol. 15 (5): 623–627. doi:10.1097/00002281-200309000-00017. PMID 12960491.
  3. ^ a b c d e Bishayee K, Khuda-Bukhsh AR (September 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy". Acta Biochim. Biophys. Sin. (Shanghai). 45 (9): 709–719. doi:10.1093/abbs/gmt064. 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. ^ Schieferdecker, Sebastian; König, Stefanie; Koeberle, Andreas; Dahse, Hans-Martin; Werz, Oliver; Nett, Markus (2015-02-27). "Myxochelins Target Human 5-Lipoxygenase". Journal of Natural Products. 78 (2): 335–338. doi:10.1021/np500909b. ISSN 0163-3864.
  6. ^ Sester, Angela; Winand, Lea; Pace, Simona; Hiller, Wolf; Werz, Oliver; Nett, Markus (2019-09-27). "Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Myxococcus xanthus Strain". Journal of Natural Products. 82 (9): 2544–2549. doi:10.1021/acs.jnatprod.9b00403. ISSN 0163-3864.
  7. ^ a b Gilbert, Nathaniel C.; Gerstmeier, Jana; Schexnaydre, Erin E.; Börner, Friedemann; Garscha, Ulrike; Neau, David B.; Werz, Oliver; Newcomer, Marcia E. (July 2020). "Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products". Nature Chemical Biology. 16 (7): 783–790. doi:10.1038/s41589-020-0544-7. ISSN 1552-4450. PMC 7747934. PMID 32393899.
  8. ^ a b "Enzymes". Hyperforin. Human Metabolome Database. 3.6. University of Alberta. 30 June 2013. Retrieved 12 December 2014. Hyperforin is found in alcoholic beverages. Hyperforin is a constituent of Hypericum perforatum (St John's Wort) Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort). The structure of hyperforin was elucidated by a research group from the Shemyakin Institute of Bio-organic Chemistry (USSR Academy of Sciences in Moscow) and published in 1975. Hyperforin is a prenylated phloroglucinol derivative. Total synthesis of hyperforin has not yet been accomplished, despite attempts by several research groups. Hyperforin has been shown to exhibit anti-inflammatory, anti-tumor, antibiotic and anti-depressant functions
    Hammer KD, Hillwig ML, Solco AK, Dixon PM, Delate K, Murphy PA, Wurtele ES, Birt DF (2007). "Inhibition of prostaglandin E(2) production by anti-inflammatory hypericum perforatum extracts and constituents in RAW264.7 Mouse Macrophage Cells". J Agric Food Chem. 55: 7323–31. doi:10.1021/jf0710074. PMC 2365463. PMID 17696442.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    Sun F, Liu JY, He F, Liu Z, Wang R, Wang DM, Wang YF, Yang DP (2011). "In-vitro antitumor activity evaluation of hyperforin derivatives". J Asian Nat Prod Res. 13: 688–99. doi:10.1080/10286020.2011.584532. PMID 21751836.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    Hübner AT (2003). "Treatment with Hypericum perforatum L. does not trigger decreased resistance in Staphylococcus aureus against antibiotics and hyperforin". Phytomedicine. 10: 206–8. doi:10.1078/094471103321659951. PMID 12725578.
    Muruganandam AV, Bhattacharya SK, Ghosal S (2001). "Antidepressant activity of hyperforin conjugates of the St. John's wort, Hypericum perforatum Linn.: an experimental study". Indian J Exp Biol. 39: 1302–4. PMID 12018529.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    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     {{cite encyclopedia}}:외부 링크 위치 quote=(도움말)
  9. ^ a b de Melo MS, Quintans Jde S, Araújo AA, Duarte MC, Bonjardim LR, Nogueira PC, Moraes VR, de Araújo-Júnior JX, Ribeiro EA, Quintans-Júnior LJ (2014). "A systematic review for anti-inflammatory property of clusiaceae family: a preclinical approach". Evid Based Complement Alternat Med. 2014: 960258. doi:10.1155/2014/960258. PMC 4058220. 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. ^ a b Wölfle U, Seelinger G, Schempp CM (February 2014). "Topical application of St. John's wort (Hypericum perforatum)". Planta Med. 80 (2–3): 109–20. doi:10.1055/s-0033-1351019. 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". {{cite journal}}:Cite 저널은 필요로 한다. journal=(도움말)
  12. ^ Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K; et al. (2011). "Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial". Cancer. 117 (16): 3788–95. doi:10.1002/cncr.25945. PMID 21287538.{{cite journal}}: CS1 maint : 복수이름 : 작성자 목록(링크)

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