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A novel synthetic HTB derivative,BECT inhibits lipopolysaccharide-mediated inflammatory response by suppressing the p38 MAPK/JNK and NF-κB activation pathways
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نویسنده
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kang s.-m. ,more s.v. ,park j.-y. ,kim b.-w. ,in p.j. ,yoon s.-h. ,choi d.-k.
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منبع
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pharmacological reports - 2014 - دوره : 66 - شماره : 3 - صفحه:471 -479
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چکیده
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Activated microglia cells are well recognized as mediators of neuroinflammation,as they release nitric oxide and pro-inflammatory cytokines in various neuroinflammatory diseases. thus,suppressing microglial activation may alleviate neuroinflammatory and neurodegenerative processes. in the present study,we synthesized and investigated the anti-neuroinflammatory effect of a novel htb (2-hydroxy-4-trifuoromethylbenzoic acid) derivative in lipopolysaccharide (lps)-stimulated microglial cells. among the synthesized derivatives,the bect [but-2-enedioic acid bis-(2-carboxy-5-trifluoromethyl- phenyl) ester] significantly decreased production of nitric oxide and other pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interleukin-6 in microglial cells. bect also mitigated the expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mrna and protein levels. further mechanistic studies demonstrated that the htb derivative inhibited phosphorylation of jnk and p38 mitogen-activated protein kinase and nuclear translocation of nuclear factor kappa-b in lps-stimulated bv-2 microglial cells. thus bect,our novel synthesized compound have anti-inflammatory activity in microglial cells,and may have therapeutic potential for treating neuroinflammatory diseases. © 2014 institute of pharmacology,polish academy of sciences. all rights reserved.
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کلیدواژه
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HTB derivative; Lipopolysaccharide; Microglia; Neurodegenerative disease; Neuroinflammation
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آدرس
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department of biotechnology,research institute for biomedical and health science,konkuk university,chungju 380-701, South Korea, department of biotechnology,research institute for biomedical and health science,konkuk university,chungju 380-701, South Korea, department of molecular science and technology,ajou university,suwon 443-749, South Korea, department of biotechnology,research institute for biomedical and health science,konkuk university,chungju 380-701, South Korea, department of biotechnology,research institute for biomedical and health science,konkuk university,chungju 380-701, South Korea, department of molecular science and technology,ajou university,suwon 443-749, South Korea, department of biotechnology,research institute for biomedical and health science,konkuk university,chungju 380-701, South Korea
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Authors
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