Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 101, Issue -, Pages 87-93Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.02.054
Keywords
Nepetin; Inflammation; ARPE-19; NF-kappa B; MAPK
Funding
- National Natural Science Foundation of China [81170828, 81670837]
- Tianjin Science & Technology Foundation [15JCZDJC35300]
- Tianjin Health and Family Planning Communication Foundation [14KG133]
- Youth Project of Tianjin Applied Basic Research and Cuttingedge Technology Research Programs [15JCQNJC45000, 15JCQNJC11000]
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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)-1 beta. Methods: The secretion and mRNA expression of inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by IL-1 beta 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-kappa B) 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 (I kappa B) and I.B 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-1 beta-induced IL-6, IL-8 and MCP-1 secretion and mRNA expression by repressing the activation of NF-kappa B 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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