Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System

Yamagishi, Sho‐ichi; Matsui, Takanori; Ishibashi, Yuji; Isami, Fumiyuki; Abe, Yumi; Sakaguchi, Tatsuya; Higashimoto, Yuichiro

doi:10.2174/1381612822666161021155502

Cited by 24 publications

(20 citation statements)

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“…Additionally, low shear stress may drive epicardial endothelial dysfunction and atherosclerosis progression, thereby causing more advanced phenotypic manifestations of CHD [52]. Studies have shown that low shear stress activated the expression of vascular cell adhesion molecule 1 (VCAM-1) which was induced by cytokines such as IL-1 and TNF-α, making the markedly greater monocyte binding to the carotid [53][54]. Nevertheless, the activation of AKT1 mediated by uid shear stress can promote cell survival in endothelial cells [55].…”

Section: Discussionmentioning

confidence: 99%

A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

Shen¹,

Wang²,

Wu³

et al. 2020

Preprint

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ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity，cytokine activity，cytokine receptor binding，steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis，AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway，Toll-like receptor signaling pathway)，and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.

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Section: Discussionmentioning

confidence: 99%

A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

Shen¹,

Wang²,

Wu³

et al. 2020

Preprint

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“… 1 – 12 ) Furthermore, there is accumulating evidence that, in the development and progression of atherosclerotic CVD, including PAD in diabetes, cumulative hyperglycemic exposure plays a central role. 2 – 6 ) Indeed, in contrast to the previous report of Haffner et al, 1 ) two clinical studies have shown that the risk of CVD in newly identified diabetic subjects or patients with a relatively short history of diabetes is not equivalent to non-diabetic individuals with a previous history of CVD, while patients with a more than 8 years history of diabetes had a comparable risk. 2 , 3 ) In addition, the association of diabetes with the increased risk of CVD death was significantly attenuated after adjusting for HbA1c, but not lipid parameters, body mass index, inflammatory biomarkers, or systolic blood pressure.…”

Section: Introductionmentioning

confidence: 85%

Role of Hyperglycemia-Induced Advanced Glycation End Product (AGE) Accumulation in Atherosclerosis

Yamagishi

Matsui

2018

Annals of Vascular Diseases

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There is a growing body of evidence that cumulative hyperglycemic exposure plays a central role in the development and progression of atherosclerotic cardiovascular disease in diabetic patients. Monosaccharides, such as glucose, fructose, and glyceraldehyde can react non-enzymatically with amino groups of proteins, lipids, nucleic acids to form senescent macromolecules termed advanced glycation end products (AGEs), whose formation and accumulation has been known to progress in diabetic patients, especially in those with a long history of disease. The sustained accumulation of AGEs could contribute to the phenomenon of metabolic memory or legacy effects observed in long-term follow-up clinical studies of diabetic patients. AGE modification alters the structural integrity and function of various types of macromolecules, and interaction of AGEs with a receptor for AGEs (RAGE) has been shown to evoke inflammatory and thrombotic reactions. Therefore, the AGE–RAGE axis is a novel therapeutic target of atherosclerotic cardiovascular disease in diabetic patients. In this paper, we briefly review the pathological role of AGEs and their receptor RAGE system in atherosclerotic cardiovascular disease, including peripheral artery disease and discuss the clinical utility of measuring AGEs in evaluating the severity of atherosclerosis in patients with diabetes.

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“…In this background, betasitosterol was reported to inhibit the expression of VEGF in kidney cancer rats, protecting functions in renal tissues [107]. Quercetin can also inhibit RAGE and reduce cardiovascular damage in diabetic nephropathy [108]. erefore, it can be speculated that inhibition of VEGF and AGE-RAGE signaling pathways may be potential treatments for proteinuria.…”

Section: Hif-1 Ras Vegf and Age-rage Signaling Pathwaymentioning

confidence: 99%

Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

Hao

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Shuangbai Tablets (SBT), a traditional herbal mixture, has shown substantial clinical efficacy. However, a systematic mechanism of its active ingredients and pharmacological mechanisms of action against proteinuria continues being lacking. A network pharmacology approach was effectual in discovering the relationship of multiple ingredients and targets of the herbal mixture. This study aimed to identify key targets, major active ingredients, and pathways of SBT against proteinuria by network pharmacology approach combined with thin layer chromatography (TLC). Human phenotype (HP) disease analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking were used in this study. To this end, a total of 48 candidate targets of 118 active ingredients of SBT were identified. Network analysis showed PTGS2, ESR1, and NOS2 to be the three key targets, and beta-sitosterol, quercetin, and berberine were the three major active ingredients; among them one of the major active ingredients, quercetin, was discriminated by TLC. These results of the functional enrichment analysis indicated that the most relevant disease including these 48 candidate proteins is proteinuria, SBT treated proteinuria by sympathetically regulating multiple biological pathways, such as the HIF-1, RAS, AGE-RAGE, and VEGF signaling pathways. Additionally, molecular docking validation suggested that major active ingredients of SBT were capable of binding to HIF-1A and VEGFA of the main pathways. Consequently, key targets, major active ingredients, and pathways based on data analysis of SBT against proteinuria were systematically identified confirming its utility and providing a new drug against proteinuria.

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Phytochemicals Against Advanced Glycation End Products (AGEs) and the Receptor System

Cited by 24 publications

References 0 publications

A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

A Network Pharmacology Analysis to Reveal the Molecular Mechanism of Zhizi-Danshen on Coronary Heart Disease

Role of Hyperglycemia-Induced Advanced Glycation End Product (AGE) Accumulation in Atherosclerosis

Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

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