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Nepetin Inhibits IL-1β Induced Inflammation via NF-κB and MAPKs Signaling Pathways in ARPE-19 Cells

Xi Chen, Ruifang Han, Peng Hao, Liming Wang, Meixin Liu, Meihua Jin, Dexin Kong, Xuan Li

Biomed Pharmacother. 2018 May;101:87-93.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP520116 Nepetin Nepetin 520-11-6 Price
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