안티유코트리엔

Antileukotriene
안티유코트리아네스
마약류
클래스 식별자
동의어로이코트리엔 수식어, 로이코트리엔 수용체 길항제
작용기전 • 효소 억제
• 수용체 길항작용
생물학적 표적 • 효소: 5-LOX; 플랩
• 수용체: CysLTRs
위키다타에서

백혈구 수식어와 백혈구 수용체 길항제라고도 알려진 항릴루코트리엔은 백혈구 관련 효소 억제제(아라크돈산 5리포크시제나아제)나 백혈구 수용체 길항제(시스티비닐로크리엔 수용체)의 기능을 하는 약물로, 결과적으로 이러한 염증 매개체의 기능에 반대한다.면역체계에 의해 다시 생성되어 천식과 COPD에서 기관지 폐쇄, 염증, 미세혈관 투과성, 점액 분비를 촉진하는 역할을 한다.[1] 백혈구 수용체 길항자를 구어적으로 백혈구라고 부르기도 한다.

몬텔루카스트, 자필루카스트, 프란루카스트 등 백혈구 수용체 길항제,[2] 질류톤, 하이퍼슘 천공과 같은 5리포크시겐효소 억제제를 사용하여 이러한 질병을 치료할 수 있다.[3][4][5][6][1] 그것들은 천식을 치료하는 데 코르티코스테로이드보다 덜 효과적이지만,[7] 특정한 마스트 세포 질환을 치료하는데 더 효과적이다.[8]

접근

백혈병의 작용을 차단하는 데는 크게 두 가지 방법이 있다.[1]

5-Lipoxygenase 경로의 억제

주요 기사: 아라키돈산 5리포크시겐아제 억제제

효소 5리폭시제네제를 억제하는 약물은 백혈구 대사 작용의 합성 경로를 억제하고,[3][4] 5리폭시제네제 활성화 단백질(FLAP)을 차단하는 MK-886과 같은 약물은 5리폭시제네제의 기능을 억제하며, 아테롬성 동맥경화증 치료에 도움을 줄 수 있다.[9]

5-LOX 억제제의 예로는 메클로페나메이트 나트륨과[10] 질류톤과 같은 약물이 있다.[10][3]

음식에서 미량에서 발견되는 일부 화학물질과 일부 건강보조식품은 바이칼레인,[10] 카페인산,[10] 쿠르쿠민,[10] 하이퍼포린[4][5][6], 세인트존스 워트 등 5-LOX를 억제하는 것으로 나타났다.[4][5][6]

시스티닐루코트리엔 1형 수용체의 길항작용

몬텔루카스트, 자프롤루카스트 등의 작용제는 수용체 길항작용에 의해 기관지 평활근과 같은 표적세포에 대한 CysLT1 수용체에서의 시스테비닐 백혈트리엔의 작용을 차단한다.

이러한 수식어는 천식 증상을 개선하고, 천식 악화를 줄이며, 말초혈액과 기관지혈 라바지액에서 어시노필 카운트와 같은 염증 표지를 제한하는 것으로 나타났다. 이것은 그들이 항염증 특성을 가지고 있다는 것을 보여준다.

참고 항목

참조

  1. ^ a b c Scott JP, Peters-Golden M (September 2013). "Antileukotriene agents for the treatment of lung disease". Am. J. Respir. Crit. Care Med. 188 (5): 538–544. doi:10.1164/rccm.201301-0023PP. PMID 23822826.
  2. ^ Singh, Rakesh Kumar; Tandon, Ruchi; Dastidar, Sunanda Ghosh; Ray, Abhijit (2013). "A review on leukotrienes and their receptors with reference to asthma". Journal of Asthma. 50 (9): 922–931. doi:10.3109/02770903.2013.823447. ISSN 0277-0903. PMID 23859232.
  3. ^ a b c "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.
  4. ^ a b c d "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 (PMID 17696442, 21751836, 12725578, 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     {{cite encyclopedia}}: 외부 링크 위치 quote= (도움말)
  5. ^ a b c 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.
  6. ^ a b c 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.
  7. ^ Fanta CH (March 2009). "Asthma". N Engl J Med. 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689.
  8. ^ Frieri M (2015). "Mast Cell Activation Syndrome". Clin Rev Allergy Immunol. doi:10.1007/s12016-015-8487-6. PMID 25944644.
  9. ^ Jawien, J.; Gajda, M.; Rudling, M.; Mateuszuk, L.; Olszanecki, R.; Guzik, T. J.; Cichocki, T.; Chlopicki, S.; Korbut, R. (March 2006). "Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice". European Journal of Clinical Investigation. 36 (3): 141–146. doi:10.1111/j.1365-2362.2006.01606.x. PMID 16506957.
  10. ^ 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.

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