Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death

Özal, Sadık Altan; Turkekul, Kader; Gürlü, Vuslat; Güçlü, Hande; Erdoğan, Suat

doi:10.1080/02713683.2018.1481517

Cited by 29 publications

(24 citation statements)

References 37 publications

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“…In addition to this, the NF-κB transcription level was partially decreased in the AlCl 3 + ESC group compared to the AlCl 3 group. It has been reported in another previous study that ESC has an anti-inflammatory effect partially by reducing NF-κB expression, which supports the results obtained in this study (Ozal et al, 2018). TNF-α initiates the cascade that enables the activation of some cytokines involved in inflammation (Kuzu et al, 2019).…”

Section: Discussionsupporting

confidence: 92%

The protective effect of esculetin against aluminium chloride‐induced reproductive toxicity in rats

et al. 2020

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The metals are ubiquitous in nature and they have a wide range of uses in industry. They remain in nature for a long time and it is very difficult for mankind to protect himself from metal exposure (Pizent et al., 2012). Aluminium is one of the most common elements in the earth's crust and takes only the value of +3 (Mayyas et al., 2005). It becomes inevitable for people to be exposed to Aluminium because of their presence in dust particles in the air, food additives, phosphate binders, antacids, buffered analgesics, antiperspirants, cooking containers, canned boxes, baby formulations, cosmetics, mining, drinking water and some herbal products

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Section: Discussionsupporting

confidence: 92%

The protective effect of esculetin against aluminium chloride‐induced reproductive toxicity in rats

et al. 2020

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“…While previous studies have reported the potential roles of MAPKs in RPE cells treated with different stimulants and inhibitors, the results are inconsistent [39,40,41,42]. To explore the importance of three separate MAPKs in retinal inflammatory diseases, ARPE-19 cells were pretreated with MAPK inhibitors (10 µM p38 inhibitor SB202190, 10 µM ERK1/2 inhibitor U0126 or 10 µM JNK inhibitor SP600125) for 1 h prior to incubation with 1 ng/mL IL-1β for 24 h. Interestingly, the MAPK inhibitors reduced the IL-1β-induced expression of sICAM-1 but not that for ICAM-1 and ICAM-1 mRNA levels (Figure 6A,B and Figure 7A).…”

Section: Resultsmentioning

confidence: 99%

Quercetin Inhibits the Production of IL-1β-Induced Inflammatory Cytokines and Chemokines in ARPE-19 Cells via the MAPK and NF-κB Signaling Pathways

Cheng

Huang

Pang

et al. 2019

IJMS

181

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Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5–20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.

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“…Some animals and microorganisms produce coumarin compounds [ 38 ]. Coumarins possess antioxidative activity [ 39 , 40 ] and esculetin is a well-established antioxidant [ 41 , 42 , 43 ]. Previous studies demonstrated that esculetin could bind to cytoplasmic Kelch-like ECH associated protein 1 (Keap1) to promote the nuclear translocation of Nrf2 in pancreatic cancer cells [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple-Purpose Connectivity Map Analysis Reveals the Benefits of Esculetin to Hyperuricemia and Renal Fibrosis

Wang

Zhu

Wang

et al. 2020

IJMS

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Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). Serum uric acid (SUA) levels in CKD stage 3–4 patients closely correlate with hyperuricemic nephropathy (HN) morbidity. New uric acid (UA)-lowering strategies are required to prevent CKD. The multiple-purpose connectivity map (CMAP) was used to discover potential molecules against HUA and renal fibrosis. We used HUA and unilateral ureteral occlusion (UUO) model mice to verify renoprotective effects of molecules and explore related mechanisms. In vitro experiments were performed in HepG2 and NRK-52E cells induced by UA. Esculetin was the top scoring compound and lowered serum uric acid (SUA) levels with dual functions on UA excretion. Esculetin exerted these effects by inhibiting expression and activity of xanthine oxidase (XO) in liver, and modulating UA transporters in kidney. The mechanism by which esculetin suppressed XO was related to inhibiting the nuclear translocation of hexokinase 2 (HK2). Esculetin was anti-fibrotic in HUA and UUO mice through inhibiting TGF-β1-activated profibrotic signals. The renoprotection effects of esculetin in HUA mice were associated with lower SUA, alleviation of oxidative stress, and inhibition of fibrosis. Esculetin is a candidate urate-lowering drug with renoprotective activity and the ability to inhibit XO, promote excretion of UA, protect oxidative stress injury, and reduce renal fibrosis.

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Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death

Abstract: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.

Cited by 29 publications

References 37 publications

The protective effect of esculetin against aluminium chloride‐induced reproductive toxicity in rats

The protective effect of esculetin against aluminium chloride‐induced reproductive toxicity in rats

Quercetin Inhibits the Production of IL-1β-Induced Inflammatory Cytokines and Chemokines in ARPE-19 Cells via the MAPK and NF-κB Signaling Pathways

Multiple-Purpose Connectivity Map Analysis Reveals the Benefits of Esculetin to Hyperuricemia and Renal Fibrosis

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