岩藻黄素通过NF-κB信号通路抑制LPS诱导的细胞炎症反应的研究
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摘要
通过已构建的THP1-Lucia/NF-κB细胞筛选系统,对岩藻黄素、虾青素、β-胡萝卜素和玉米黄质等4种海洋来源的类胡罗卜素化合物进行抗炎活性筛选,结果发现岩藻黄素具有良好的抗炎活性.在此基础,进一步研究岩藻黄素对NF-κB信号通路的调控机制,结果揭示了岩藻黄素能通过抑制IκB-α的细胞质降解和NF-κB蛋白的磷酸化,进而抑制由LPS诱导的细胞炎症因子的产生,从而达到抗炎效果.
In this study,four marine-derived carotenoid compounds,such as fucoxanthin,astaxanthin,β-carotene and zeaxanthin,were tested using the established THP1-Lucia/NF-κB cell screening system. Screening for anti-inflammatory activity revealed that fucoxanthin has good anti-inflammatory activities. On this basis,the regulation mechanism of fucoxanthin on NF-κB signaling pathway was further studied. The results revealed that fucoxanthin inhibited the cytoplasmic degradation of IκB-α and phosphorylation of NF-κB,so that the production of cellular inflammatory factors induced by LPS were inhibited.
In this study,four marine-derived carotenoid compounds,such as fucoxanthin,astaxanthin,β-carotene and zeaxanthin,were tested using the established THP1-Lucia/NF-κB cell screening system. Screening for anti-inflammatory activity revealed that fucoxanthin has good anti-inflammatory activities. On this basis,the regulation mechanism of fucoxanthin on NF-κB signaling pathway was further studied. The results revealed that fucoxanthin inhibited the cytoplasmic degradation of IκB-α and phosphorylation of NF-κB,so that the production of cellular inflammatory factors induced by LPS were inhibited.
引文
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[36] GAMMONE M A,D'ORAZIO N. Anti-obesity activity of the marine carotenoid fucoxanthin[J]. Marine Drugs,2015,13(4):2196-2214.
[37] ROBERTSON R C,GUIHENEUF F,BAHAR B,et al. The anti-inflammatory effect of algae-derived lipid extracts onlipopolysaccharide(LPS)-stimulated human THP-1 macrophages[J]. Marine Drugs,2015,13(8):5402-5224.
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[3] TUNG Y T,CHUA M T,WANG S Y,et al. Anti-inflammation activities of essential oil and its constituents from indige-nous cinnamon(Cinnamomum osmophloeum)twigs[J]. Bioresour Technol,2008,99(9):3908-3913.
[4] ZHANG Q J,LENARDO M,BALTIMORE D. 30 Years of NF-κB:a blossoming of relevance to human pathobiology[J]. Cell,2017,168:37-57.
[5] HAYDEN M S,GHOSH S. Shared principles in NF-kappaB signaling[J]. Cell,2008,132(3):344-362.
[6] HOESEL B,SCHMID J A. The complexity of NF-κB signaling in inflammation and cancer[J]. Molecular Cancer,2013,12(1):86.
[7] HOSHINO K,TAKEUCHI O,KAWAI T,et al. Cutting edge:Toll-like receptor 4(TLR4)-deficient mice are hypore-sponsive to lipopolysaccharide:evidence for TLR4 as the Lps gene product[J]. Journal of Immunology,1999,162(7):3749-3752.
[8] MEHBUB M F,PERKINS M V,ZHANG W,et al. New marine natural products from sponges(Porifera)of the orderDictyoceratida(2001 to 2012); a promising source for drug discovery,exploration and future prospects[J]. Biotechnolo-gy Advances,2016,34(5):473-491.
[9] RAVI KUMAR S,BHASKAR N,BASKARAN V. Comparative effects ofβ-carotene and fucoxanthin on retinol deficiencyinduced oxidative stress in rats[J]. Molecular&Cellular Biochemistry,2009,331:59-67.
[10] MAOKA T,NISHINO A,YASUI H,et al. Anti-Oxidative activity of mytiloxanthin,a metabolite of fucoxanthin inshellfish and tunicates[J/OL]. Marine Drugs,2016,14(5):93. DOI:10. 3390/md1450093.
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[12] BERTOLINI A,OTTANI A,SANDRINI M. Dual acting anti-inflammatory drugs:a reappraisal[J]. PharmacologicalResearch,2001,44(6):437-450.
[13] LIND L. Circulating markers of inflammation and atherosclerosis[J]. Atherosclerosis,2003,169(2):203-214.
[14] TILG H,WILMER A,VOGEL W,et al. Serum levels of cytokines in chronic liver diseases[J]. Gastroenterology,1992,103(1):264-274.
[15] GHOSH S,KARIN M. Missing pieces in the NF-kappaB puzzle[J]. Cell,2002,109(4):S81-S96.
[16] POLARI L,WIKLUND A,SOUSA S,et al. SERMs promote anti-inflammatory signaling and phenotype of CD14+Cells[J]. Inflammation,2018,41(4):1157-1171.
[17] LENDERMON E A,COON T A,BEDNASH J S,et al. Azithromycin decreases NALP3 mRNA stability in monocytes tolimit inflammasome-dependent inflammation[J]. Respiratory Research,2017,18(1):131.
[18] STABLER T V,HUANG Z,MONTELL E,et al. Chondroitin sulphate inhibits NF-kappaB activity induced by interac-tion of pathogenic and damage associated molecules[J]. Osteoarthritis Cartilage,2017,25(1):166-174.
[19] TIKHANOVICH I,KURAVI S,ARTIGUES A,et al. Dynamic arginine methylation of tumor necrosis factor(TNF)re-ceptor-associated factor 6 regulates toll-like receptor signaling[J]. Journal of Biological Chemistry,2015,290(36):22236-22249.
[20] LI Y,WANG X,REN J,et al. Identification and application of anti-inflammatory compounds screening system basedon RAW264. 7 cells stably expressing NF-kappaB-dependent SEAP reporter gene[J]. BMC Pharmacol Toxicol,2017,18(1):5-17.
[21] SUGAWARA T,BASKARAN V,TSUZUKI W,et al. Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during ab-sorption by Caco-2 human intestinal cells and mice[J]. Journal of Nutrition,2002,132(5):946-951.
[22] HUI Z,YIBO T,YING Z,et al. Fucoxanthin:a promising medicinal and nutritional ingredient[J]. Evidence-BasedComplementary and Alternative Medicine,2015,2015(9):1-10.
[23] MATSUNO T. Aquatic animal carotenoids[J]. Fisheries Science,2001,67(5):771–783.
[24] PENG J,YUAN J P,WU C F,et al. Fucoxanthin,a marine carotenoid present in brown seaweeds and diatoms:me-tabolism and bioactivities relevant to human health[J]. Marine Drugs,2011,9(10):1806-1828.
[25] TAKAICHI S. Carotenoids in algae:distributions,biosyntheses and functions[J]. Marine Drugs,2011,9(6):1101-1118.
[26] MIKAMI K,HOSOKAWA M. Biosynthetic pathway and health benefits of fucoxanthin,an algae-specific xanthophyll inbrown seaweeds[J]. International Journal of Molecular Sciences,2013,14(7):13763-13781.
[27] QIUTANG L. NF-kappaB regulation in the immune system[J]. Nature Reviews Immunology,2002,10(2):725-734.
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[29] AGGARWAL B B,NATARAJAN K. Tumor necrosis factors:developments during the last decade[J]. European Cyto-kine Network,1996,7(2):93-124.
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[36] GAMMONE M A,D'ORAZIO N. Anti-obesity activity of the marine carotenoid fucoxanthin[J]. Marine Drugs,2015,13(4):2196-2214.
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[39] JUNG H,LEE D S,PARK S K,et al. Fucoxanthin inhibits myofibroblast differentiation and extracellular matrix pro-duction in nasal polyp-derived fibroblasts via modulation of smad-dependent and smad-independent signaling pathways[J]. Marine Drugs,2018,16(9):323. DOI:10. 3390/md16090323.
[40] CHOI J H,KIM N H,KIM S J,et al. Fucoxanthin inhibits the inflammation response in paw edema model through sup-pressing MAPKs,Akt,and NFκB[J]. Journal of Biochemical and Molecular Toxicology,2016,30(3):111-119.