Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

Cui, Zhifu; Zhao, Xingtao; Amevor, Felix Kwame; Du, Xiaxia; Wang, Yan; Li, Diyan; Shu, Gang; Tian, Yaofu; Zhao, Xiaoling

doi:10.3389/fimmu.2022.943321

Cited by 172 publications

(92 citation statements)

References 256 publications

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“…At the same time, a variety of small molecules compounds and natural products can act on SIRT1 to different degrees, and our current research has also confirmed that SIRT1 plays an important role in the development of endocrine and metabolic disorders. Notably, the above effects may be caused by different action mechanisms of SIRT1 streets, such as SIRT1/Keap1/Nrf2/HO-1 and PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB mediated inflammatory response, SIRT1/PGC1α mediated mitochondrial damage, and SIRT1/FOXO mediated autophagy 237 . These evidences provide a theoretical basis for SIRT1 as a therapeutic target for endocrine and metabolic diseases.…”

Section: Discussionmentioning

confidence: 99%

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Lu¹,

Zhao²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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Silent information regulator 1 (SIRT1), a highly conserved NAD + -dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases. These evidences indicate that targeting SIRT1 has promising applications in the treatment of endocrine and metabolic diseases. This review focuses on the role of SIRT1 in endocrine and metabolic diseases. First, we describe the background and structure of SIRT1. Then, we outline the role of SIRT1 in endocrine and metabolic diseases such as hyperuricemia, diabetes, hypertension, hyperlipidemia, osteoporosis, and polycystic ovarian syndrome. Subsequently, the SIRT1 agonists and inhibitors in the above diseases are summarized and future research directions are proposed. Overall, the information presents here may highlight the potential of SIRT1 as a future biomarker and therapeutic target for endocrine and metabolic diseases.

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Section: Discussionmentioning

confidence: 99%

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Lu¹,

Zhao²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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“…Previous study by Tangsaengvit et al has reported that lower concentration of quercetin (1 nM) significantly increased the amount of neuritis and neurite length via the activation of P13K/AKT pathway (Tangsaengvit et al, 2013). However, mechanistically, quercetin activates or inactivates the expression of several additional signaling cascades, i.e., mitogen-activated protein kinases (MAPKs), mitophagy activation, sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) pathway (Cen et al, 2022; Cui et al, 2022; Spencer et al, 2003; Xie et al, 2022). Further studies are needed to elucidate the neuroprotective effect of quercetin in vivo with a more systematic approach.…”

Section: Discussionmentioning

confidence: 99%

Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

Tang

Guo

Peng

et al. 2022

Preprint

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Abnormal amyloid-β (Aβ) abnormal accumulation and oxidative stress play important roles in Alzheimer′ disease (AD). Quercetin has been reported to possess antioxidant and anti-inflammatory properties, and thus of therapeutic interests for neurodegenerative disorders. In the present study, we aimed to characterize the mechanisms by which quercetin exerts neuroprotective effects in murine neuroblastoma N2a cells stably expressing human Swedishh mutant amyloid precursor protein (APP). Quercetin treatment exhibited low cytoxicity, attenuated APP expression and APP-induced oxidative neurotoxicity in N2a/APP cells. We found that quercetin effected via the down-regulation of phospho-extracellular signal regulated protein kinase (p-ERK1/2) pathway and up-regulation of phospho-protein kinase B (p-AKT) pathway in N2a/APP cells. In addition, quercetin ameliorated the elevated levels of reactive oxygen species using DCFH-DA flow-cytometry in N2a/APP cells, lipid peroxidation using (4-HNE), and DNA oxidation (8-OHdG assays). Quercetin ameliorated the loss of mitochondrial membrane potential using JC-1 fluorescence assay in N2a/APP cells in a dose-dependent mannor. In conclusion, we domenstrated the neuroprotective effects of quercetin against the APP expression induced oxidative neurotoxicity, impairment of mitochondrial function and oxidative stress through inactivation of the ERK1/2 signaling pathway and activation of AKT signaling pathways.

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“…Several investigations attribute these benefits to increased Sirt-1 activity. Sirt-1 is part of the sirtuin family, a class of nutrient-sensitive regulators of epigenetic information capable of modulating senescence and cell lifespan, and is therefore associated with longevity [ 133 , 134 , 135 , 136 , 137 ]. Sirt1 is an NAD + -dependent deacetylase and targets several transcription factors involved in adaptive responses to cellular stress, such as NF-κB, forkhead transcription factor (FOXO) 1, 3 and 4, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) and p53.…”

Section: Effects Of Polyphenols On Deregulated Nutrient-sensing Pathwaysmentioning

confidence: 99%

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

Pereira

Santos

Fortunato

et al. 2023

IJMS

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Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects.

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Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

Cited by 172 publications

References 256 publications

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Novel Role of the SIRT1 in Endocrine and Metabolic Diseases

Quercetin reduces APP expression, oxidative stress and mitochondrial dysfunction in the N2a/APPswe cells via ERK1/2 and AKT pathways

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

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