Effects of quercetin on diabetic retinopathy and its association with NLRP3 inflammasome and autophagy

Li, Rong; Chen, Lin; Yao, Guomin; Yan, Honglin; Wang, Li

doi:10.18240/ijo.2021.01.06

Cited by 28 publications

(18 citation statements)

References 30 publications

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“…In subsequent studies, GHSR-1a siRNA was used to block the effect of ghrelin. The results showed that the viability of HRMECs in the high-glucose group was significantly reduced, consistent with our previous results [ 26 ]. The viability of cells treated with exogenous ghrelin was significantly greater than that of cells in the high-glucose group.…”

Section: Discussionsupporting

confidence: 92%

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

Yao

Zhou

et al. 2022

Eye and Vis

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Background To investigate the effect of ghrelin, a brain-gut peptide hormone, on high glucose-induced retinal angiogenesis in vitro and explore its association with endoplasmic reticulum (ER) stress. Methods Human retinal microvascular endothelial cells (HRMECs) were first divided into control and high-glucose groups, and the mRNA and protein expression levels of the receptor for ghrelin [growth hormone secretin receptor 1a, (GHSR-1a)] in cells were determined. HRMECs were then treated with high glucose alone or in combination with ghrelin or siGHSR-1a, and cell viability, migration, tube formation and the expression of the ER stress-related proteins PERK, ATF4 and CHOP were detected. Finally, to clarify whether the effects of ghrelin are related to ER stress, tunicamycin, an inducer of ER stress, was used to treat HRMECs, and cell viability, cell migration, and tube formation were evaluated. Results GHSR-1a expression in HRMECs at both the mRNA and protein levels was inhibited by high-glucose treatment. Under high-glucose conditions, ghrelin promoted cell viability and inhibited migration and tube formation, which were blocked by siGHSR-1a treatment. Ghrelin inhibited the increases in the protein levels of p-PERK, ATF4 and CHOP induced by high-glucose treatment, and combination treatment with siGHSR-1a reversed this effect of ghrelin. When tunicamycin was added, the effects of ghrelin on cell viability, migration and tube formation were all weakened. Conclusions This study experimentally revealed that ghrelin can inhibit high glucose-induced retinal angiogenesis in vitro through GHSR-1a, and alleviation of ER stress may be one of the mechanisms underlying this effect.

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Section: Discussionsupporting

confidence: 92%

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

Yao

Zhou

et al. 2022

Eye and Vis

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“…In ischemic or traumatic brain cells, binding of glibenclamide to SUR1-TRPM4 reduces depolarization, which reduces blood–brain barrier breakdown and vasogenic edema [ 42 ]. In addition, in the retina, glibenclamide anti-edematous effects could result from the inhibition of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome and related neuroinflammation [ 43 ], known to be involved in diabetic retinopathy mechanisms [ 44 , 45 , 46 ]. In clinical studies, whether glibenclamide or other sulfonylurea drugs could improve the management of patients with diabetic macular edema has not been demonstrated, but the present result could prompt further studies on the subject.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model

et al. 2021

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Diabetic retinopathy (DR) remains a major cause of vision loss, due to macular edema, retinal ischemia and death of retinal neurons. We previously demonstrated that acute administration of glibenclamide into the vitreous, or given orally at a non-hypoglycemic dose, protected the structure and the function of the retina in three animal models that each mimic aspects of diabetic retinopathy in humans. In this pilot study, we investigated whether one year of chronic oral glibenclamide, in a non-hypoglycemic regimen (Amglidia®, 0.4 mg/kg, Ammtek/Nordic Pharma, 5 d/week), could alleviate the retinopathy that develops in the Goto-Kakizaki (GK) rat. In vivo, retinal function was assessed by electroretinography (ERG), retinal thickness by optical coherence tomography (OCT) and retinal perfusion by fluorescein and indocyanin green angiographies. The integrity of the retinal pigment epithelium (RPE) that constitutes the outer retinal barrier was evaluated by quantitative analysis of the RPE morphology on flat-mounted fundus ex vivo. Oral glibenclamide did not significantly reduce the Hb1Ac levels but still improved retinal function, as witnessed by the reduction in scotopic implicit times, limited diabetes-induced neuroretinal thickening and the extension of ischemic areas, and it improved the capillary coverage. These results indicate that low doses of oral glibenclamide could still be beneficial for the prevention of type 2 diabetic retinopathy. Whether the retinas ofpatients treated specifically with glibenclamideare less at risk of developing diabetic complications remains to be demonstrated.

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“…Quercetin promotes and protects the function of the intestinal tight junction barrier ( 25 ) and degrades some intestinal bacteria, decreasing their amount in a time-dependent manner ( 26 ). It also protects human retinal microvascular endothelial cells from the high-glucose-induced injury by inhibiting the expression of NLRP3, caspase-1, IL-1 β, and IL-18 ( 27 ) and inhibits the expression of NLRP3, caspase-1, iNOS, and inflammatory factors in the LPS-activated mononuclear macrophages, consequently improving their antioxidant and anti-inflammatory abilities ( 28 ). Therefore, quercetin protects the integrity of the tight junction barrier and exerts a regulatory effect on the NLRP3 inflammasome.…”

Section: Popular Scientific Summarymentioning

confidence: 99%

Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathway in vivo and in vitro

Zhang

Liu

et al. 2022

Food & Nutrition Research

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Background: Inflammatory bowel diseases are characterized by the alterations of the mucosa and gastrointestinal physiology, and the core of these alterations is endothelial cells. Quercetin is a flavonoid presents in some traditional Chinese medicine, plants, and fruits. Its protective effects in several gastrointestinal tumors have been demonstrated, but its effects on bacterial enteritis and pyroptosis-related diseases have rarely been studied. Objective: This study aimed to evaluate the effect of quercetin on bacterial enteritis and pyroptosis. Design: In vitro experiments were performed using rat intestinal microvascular endothelial cells divided into seven groups: control group (no treatment), model group (10 μg/mL lipopolysaccharide (LPS)+1 mM adenosine triphosphate [ATP]), LPS group (10 μg/mL LPS), ATP group (1 mM ATP), and treatment groups (10 μg/mL LPS+1 mM ATP and 5, 10, and 20 μM quercetin). The expression of pyroptosis-associated proteins, inflammatory factors, tight junction proteins, and the percentage of late apoptotic and necrotic cells were measured. In vivo analysis was performed using specific pathogen-free Kunming mice pretreated with quercetin and the water extract of Cacumen Platycladi for 2 weeks followed by 6 mg/kg LPS on day 15. Inflammation in the blood and intestinal pathological changes were evaluated. Results: Quercetin used in vitro significantly reduced the expression of Toll-like receptor 4 (TLR4), NOD-like receptor 3 (NLRP3), caspase-1, gasdermin D, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor-α. It also inhibited phosphorylation of nuclear factor-kappa B (NF-κB) p65 and increased cell migration and the expression of zonula occludens 1 and claudins, while reduced the number of late apoptotic cells. The in vivo results showed that Cacumen Platycladi and quercetin significantly reduced inflammation, protected the structure of the colon and cecum, and prevent fecal occult blood induced by LPS. Conclusions: These findings suggested the ability of quercetin to reduce inflammation induced by LPS and pyroptosis through TLR4/NF-κB/NLRP3 pathway.

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Effects of quercetin on diabetic retinopathy and its association with NLRP3 inflammasome and autophagy

Cited by 28 publications

References 30 publications

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model

Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathway in vivo and in vitro

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