Glycyrrhizin Protects the Diabetic Retina against Permeability, Neuronal, and Vascular Damage through Anti-Inflammatory Mechanisms

Liu, Li; Jiang, Youde; Steinle, Jena J.

doi:10.3390/jcm8070957

Cited by 31 publications

(30 citation statements)

References 38 publications

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“…In contrast, plant-derived antidiabetic agents can alleviate diabetic complications through glycaemic control, antioxidant mechanism, and inhibition of pathological signal transductions involved in inflammation, fibrosis, and apoptosis ( Figure 2). Curcumin [73], resveratrol [74], naringenin [34], quercetin [75], apigenin [76,77], myricitrin [78,79], baicalin [80,81], luteolin [82,83], mangiferin [59,84,85], emodin [86,87], rosmarinic acid [88], berberine [89], stevioside [90,91], asiatic acid [92][93][94], glycyrrhizin [95][96][97][98], baicalin [99,100], silymarin [101], gallic acid [102][103][104], catechins [105,106], thymoquinone [107], and ferulic acid [108][109][110] have been revealed to attenuate diabetic vascular complications via modulating multiple molecular targets.…”

Section: Plant-derived Small Molecules As Antidiabetic Agentsmentioning

confidence: 99%

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Dewanjee

Chakraborty

Mukherjee

et al. 2020

IJMS

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Diabetes mellitus is a life-threatening metabolic syndrome. Over the past few decades, the incidence of diabetes has climbed exponentially. Several therapeutic approaches have been undertaken, but the occurrence and risk still remain unabated. Several plant-derived small molecules have been proposed to be effective against diabetes and associated vascular complications via acting on several therapeutic targets. In addition, the biocompatibility of these phytochemicals increasingly enhances the interest of exploiting them as therapeutic negotiators. However, poor pharmacokinetic and biopharmaceutical attributes of these phytochemicals largely restrict their clinical usefulness as therapeutic agents. Several pharmaceutical attempts have been undertaken to enhance their compliance and therapeutic efficacy. In this regard, the application of nanotechnology has been proven to be the best approach to improve the compliance and clinical efficacy by overturning the pharmacokinetic and biopharmaceutical obstacles associated with the plant-derived antidiabetic agents. This review gives a comprehensive and up-to-date overview of the nanoformulations of phytochemicals in the management of diabetes and associated complications. The effects of nanosizing on pharmacokinetic, biopharmaceutical and therapeutic profiles of plant-derived small molecules, such as curcumin, resveratrol, naringenin, quercetin, apigenin, baicalin, luteolin, rosmarinic acid, berberine, gymnemic acid, emodin, scutellarin, catechins, thymoquinone, ferulic acid, stevioside, and others have been discussed comprehensively in this review.

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Section: Plant-derived Small Molecules As Antidiabetic Agentsmentioning

confidence: 99%

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Dewanjee

Chakraborty

Mukherjee

et al. 2020

IJMS

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“…The anti-inflammatory effects of GA were mediated by the inhibition of TNF-⍺, IL-1β, and the cleavage of caspase-3 in retinal EC. GA, through the inhibition of HMGB1, reduces ROS concentrations and blood circulating glucose [ 99 ]. In another work, GA reduced TLR-4 concentrations and ischemia-reperfusion damage as well as increasing the expression of insulin receptors, partially preserving the anatomical integrity of the retina [ 100 ].…”

Section: Future Therapeutic Approachesmentioning

confidence: 99%

The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies

et al. 2020

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High-mobility group box 1 (HMGB1) is a protein that is part of a larger family of non-histone nuclear proteins. HMGB1 is a ubiquitary protein with different isoforms, linked to numerous physiological and pathological pathways. HMGB1 is involved in cytokine and chemokine release, leukocyte activation and migration, tumorigenesis, neoangiogenesis, and the activation of several inflammatory pathways. HMGB1 is, in fact, responsible for the trigger, among others, of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4), and vascular endothelial growth factor (VEGF) pathways. Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) that is rapidly growing in number. DR is an inflammatory disease caused by hyperglycemia, which determines the accumulation of oxidative stress and cell damage, which ultimately leads to hypoxia and neovascularization. Recent evidence has shown that hyperglycemia is responsible for the hyperexpression of HMGB1. This protein activates numerous pathways that cause the development of DR, and HMGB1 levels are constantly increased in diabetic retinas in both proliferative and non-proliferative stages of the disease. Several molecules, such as glycyrrhizin (GA), have proven effective in reducing diabetic damage to the retina through the inhibition of HMGB1. The main focus of this review is the growing amount of evidence linking HMGB1 and DR as well as the new therapeutic strategies involving this protein.

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“…In acute diabetic studies, glycyrrhizin reduced HMGB1, ERK1/2, caspase 3 and glutamate levels [13]. We have used glycyrrhizin to show that inhibition of HMGB1 protected the retina against I/R-induced damage [14], as well as chronic diabetes-induced damage [15].…”

Section: Introductionmentioning

confidence: 99%

Epac1 and Glycyrrhizin Both Inhibit HMGB1 Levels to Reduce Diabetes-Induced Neuronal and Vascular Damage in the Mouse Retina

Liu

Jiang

Steinle

2019

JCM

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The role of high mobility group box 1 (HMGB1) in acute diabetic retinal damage has been demonstrated. We recently reported that glycyrrhizin, a HMGB1 inhibitor, protected the diabetic retina against neuronal, vascular, and permeability changes. In this study, we wanted to investigate the role of exchange protein for cAMP 1 (Epac1) on HMGB1 and the actions of glycyrrhizin. Using endothelial cell specific knockout mice for Epac1, we made some mice diabetic using streptozotocin, and treated some with glycyrrhizin for up to 6 months. We measured permeability, neuronal, and vascular changes in the Epac1 floxed and knockout mice. We also investigated whether Epac1 and glycyrrhizin work synergistically to reduce the retinal inflammatory mediators, tumor necrosis factor alpha (TNFα) and interleukin-1-beta (IL1β), as well as sirtuin 1 (SIRT1) levels. Epac1 and glycyrrhizin reduced inflammatory mediators with synergistic actions. Glycyrrhizin also increased SIRT1 levels in the Epac1 mice. Overall, these studies demonstrate that glycyrrhizin and Epac1 can work together to protect the retina. Finally, glycyrrhizin may regulate HMGB1 through increased SIRT1 actions.

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Glycyrrhizin Protects the Diabetic Retina against Permeability, Neuronal, and Vascular Damage through Anti-Inflammatory Mechanisms

Cited by 31 publications

References 38 publications

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies

Epac1 and Glycyrrhizin Both Inhibit HMGB1 Levels to Reduce Diabetes-Induced Neuronal and Vascular Damage in the Mouse Retina

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