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  • Title: Nepetin inhibits IL-1β induced inflammation via NF-κB and MAPKs signaling pathways in ARPE-19 cells.
    Author: Chen X, Han R, Hao P, Wang L, Liu M, Jin M, Kong D, Li X.
    Journal: Biomed Pharmacother; 2018 May; 101():87-93. PubMed ID: 29477475.
    Abstract:
    BACKGROUNDS: Chronic inflammation in retinal pigment epithelial (RPE) cells is related to the pathogenesis of retinal inflammatory blind causing diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Nepetin, a natural flavonoid compound, has shown potent anti-inflammatory activities but has not been studied on ocular resident cells yet. Here, we assess the ability of Nepetin to alleviate the inflammatory responses of ARPE-19 cells induced by interleukin (IL)-1β. METHODS: The secretion and mRNA expression of inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by IL-1β are measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) respectively. To clarify the underlying action mechanism, we examine the effect of Nepetin on activation of nuclear factor of kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways using Western blot. RESULTS: Nepetin can significantly decrease the three inflammatory mediators at both protein and mRNA level in a dose-dependent manner. Western blot results show that Nepetin can decrease the nuclear translocation of p65 through suppressing phosphorylation of inhibitor of nuclear factor kappa B (IκB) and IκB kinase (IKK). Also, Nepetin can decrease the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, c-Jun N-terminal kinase (JNK) and p38 MAPK. CONCLUSIONS: Taken together, Nepetin abolishes IL-1β-induced IL-6, IL-8 and MCP-1 secretion and mRNA expression by repressing the activation of NF-κB and MAPKs. These results indicate that Nepetin shows potential to be used for prevention and treatment of inflammatory retinal diseases or as a lead compound.
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