PMID- 29477475 OWN - NLM STAT- MEDLINE DCOM- 20180924 LR - 20180924 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 101 DP - 2018 May TI - Nepetin inhibits IL-1beta induced inflammation via NF-kappaB and MAPKs signaling pathways in ARPE-19 cells. PG - 87-93 LID - S0753-3322(17)36759-8 [pii] LID - 10.1016/j.biopha.2018.02.054 [doi] AB - 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)-1beta. METHODS: The secretion and mRNA expression of inflammatory cytokines IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) induced by IL-1beta 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-kappaB) 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 (IkappaB) and IkappaB 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-1beta-induced IL-6, IL-8 and MCP-1 secretion and mRNA expression by repressing the activation of NF-kappaB 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. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Chen, Xi AU - Chen X AD - 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. FAU - Han, Ruifang AU - Han R AD - 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. FAU - Hao, Peng AU - Hao P AD - 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. FAU - Wang, Liming AU - Wang L AD - 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. FAU - Liu, Meixin AU - Liu M AD - 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. FAU - Jin, Meihua AU - Jin M AD - Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. FAU - Kong, Dexin AU - Kong D AD - 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. FAU - Li, Xuan AU - Li X AD - 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: xuanli08@yahoo.com. LA - eng PT - Journal Article DEP - 20180223 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Flavones) RN - 0 (Flavonoids) RN - 0 (Interleukin-1beta) RN - 0 (NF-kappa B) RN - I3O7LF3GED (eupafolin) SB - IM MH - Cell Line MH - Cell Survival/drug effects/physiology MH - Dose-Response Relationship, Drug MH - Flavones/*pharmacology/therapeutic use MH - Flavonoids/*pharmacology/therapeutic use MH - Humans MH - Inflammation/chemically induced/metabolism/prevention & control MH - Interleukin-1beta/antagonists & inhibitors/*toxicity MH - MAP Kinase Signaling System/drug effects/*physiology MH - NF-kappa B/antagonists & inhibitors/*metabolism MH - Retinal Pigment Epithelium/cytology/drug effects/*metabolism OTO - NOTNLM OT - ARPE-19 OT - Inflammation OT - MAPK OT - NF-kappaB OT - Nepetin EDAT- 2018/02/27 06:00 MHDA- 2018/09/25 06:00 CRDT- 2018/02/26 06:00 PHST- 2017/12/10 00:00 [received] PHST- 2018/02/08 00:00 [revised] PHST- 2018/02/13 00:00 [accepted] PHST- 2018/02/27 06:00 [pubmed] PHST- 2018/09/25 06:00 [medline] PHST- 2018/02/26 06:00 [entrez] AID - S0753-3322(17)36759-8 [pii] AID - 10.1016/j.biopha.2018.02.054 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 May;101:87-93. doi: 10.1016/j.biopha.2018.02.054. Epub 2018 Feb 23.