Nepetin inhibits IL-1β induced inflammation via NF-κB and MAPKs signaling pathways in ARPE-19 cells

  • Biomed Pharmacother. 2018 May;101:87-93. doi: 10.1016/j.biopha.2018.02.054.
Xi Chen  1 ,  Ruifang Han  2 ,  Peng Hao  2 ,  Liming Wang  2 ,  Meixin Liu  2 ,  Meihua Jin  3 ,  Dexin Kong  4 ,  Xuan Li  5
Affiliations
  • 1. Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China; Nankai University Affiliated Eye Hospital, Nankai University, Tianjin 300020, China; Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
  • 2. Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China; Nankai University Affiliated Eye Hospital, Nankai University, Tianjin 300020, China.
  • 3. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
  • 4. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
  • 5. Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China; Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China; Nankai University Affiliated Eye Hospital, Nankai University, Tianjin 300020, China. Electronic address: [email protected].
PMID: 29477475 DOI: 10.1016/j.biopha.2018.02.054
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.

Keywords
ARPE-19; Inflammation; MAPK; NF-κB; Nepetin.
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