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

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in treatment of aging-related diseases. Sirtuin 1 (SIRT1), member NAD+-dependent deacetylase enzyme family, is extensively explored as potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against diseases such Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) reperfusion (MI/R), Atherosclerosis (AS), Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, regulates cellular senescence multiple processes, including SIRT1/Keap1/Nrf2/HO-1 SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mitochondrial damage, SIRT1/FoxO autophagy, SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin neuroprotective effects. In this review, we summarized improvement attenuation effect quercetin on relationship between relevant signaling pathways by SIRT1. Moreover, functional regulation markers function, autophagy apoptosis through was discussed. Finally, prospects extracellular vesicles (EVs) loading delivery, SIRT1-mediated EVs signal carriers treating diseases, well discussed ferroptosis alleviation to protect via activating Generally, may serve promising inhibiting reducing responses, restoring dysfunction.

Language: Английский

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Apoptotic Mechanisms of Quercetin in Liver Cancer: Recent Trends and Advancements

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 712 - 712

Published: Feb. 20, 2023

Due to rising incidence rates of liver cancer and worries about the toxicity current chemotherapeutic medicines, hunt for further alternative methods treat this malignancy has escalated. Compared chemotherapy, quercetin, a flavonoid, is relatively less harmful normal cells regarded as an excellent free-radical scavenger. Apoptotic cell death caused by quercetin been demonstrated many prior studies. It present in fruits, vegetables, herbs. Quercetin targets apoptosis, upregulating Bax, caspase-3, p21 while downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, Bcl-2. Additionally, it reported increase STAT3 protein degradation decreasing activation. potential future chemoprevention, based on substantial research its anticancer effects. The review discusses quercetin’s mechanisms action, nanodelivery strategies, other cellular effects cancer.

Language: Английский

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Quercetin, a Flavonoid with Great Pharmacological Capacity

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1000 - 1000

Published: Feb. 25, 2024

Quercetin is a flavonoid with low molecular weight that belongs to the human diet’s phenolic phytochemicals and nonenergy constituents. has potent antioxidant capacity, being able capture reactive oxygen species (ROS), nitrogen (RNS), chlorine (ROC), which act as reducing agents by chelating transition-metal ions. Its structure five functional hydroxyl groups, work electron donors are responsible for capturing free radicals. In addition its different pharmacological properties of quercetin have been described, such carcinostatic properties; antiviral, antihypertensive, anti-inflammatory ability protect low-density lipoprotein (LDL) oxidation, inhibit angiogenesis; these developed in this review.

Language: Английский

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Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Language: Английский

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Therapeutic detoxification of quercetin for aflatoxin B1-related toxicity: Roles of oxidative stress, inflammation, and metabolic enzymes

Environmental Pollution, Journal Year: 2024, Volume and Issue: 345, P. 123474 - 123474

Published: Feb. 1, 2024

Language: Английский

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Quercetin Protects Ethanol-Induced Hepatocyte Pyroptosis via Scavenging Mitochondrial ROS and Promoting PGC-1α-Regulated Mitochondrial Homeostasis in L02 Cells

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 15

Published: July 16, 2022

Alcoholic liver disease (ALD) is a multifaceted process that involves excessive lipid, reactive oxygen species (ROS) production, unbalanced mitochondrial homeostasis, and ultimate cell death. Quercetin dietary phytochemical presented in various fruits vegetables, which has anti-inflammatory antioxidant effects. According to recent advances pharmanutritional management, the effects of quercetin on processes have attracted attention. In study, we explored whether could attenuate ethanol-induced hepatocyte pyroptosis by maintaining homeostasis studied its hepatoprotective effect underlying mechanism. We chose L02 cells establish an vitro model with pyroptosis. Then, at approximately 80% confluence were treated (80, 40, 20 μM). The viability (CCK-8) was used investigate proliferation. Relative assay kits measure oxidative stress index ( OSI = TOS / TAS ), lipid peroxidation (LPO) release, membrane potential δ Ψ m ). morphology mitochondria characterized transmission electron microscopy- (TEM-) based analysis. Mitochondrial dynamics (Mito Tracker Green), mitROS (MitoSOX Red Superoxide) nuclear DNA (nDNA) damage (γH2AX) markers detected immunofluorescence. mRNA levels function (including (mtDNA) transcription genes TWNK, MTCO1, MFND) pyroptosis-related RT-qPCR, protein NLRP3, ASC, caspase1, cleaved-caspase1, IL-18, IL-1β, GSDMD-N western blot. results showed treatment downregulated redox status, droplets, LPO restored damaged potential, repaired mtDNA damage, PGC-1α transfer, dynamics. gene expressions decreased, effectively inhibited Therefore, indicated protected via scavenging promoting PGC-1α-mediated cells.

Language: Английский

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Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1212 - 1212

Published: June 3, 2023

Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation antioxidant defenses results overproduction subsequent oxidative damage to biomolecules cellular components that disturb function. Oxidative stress contributes initiation progression liver pathologies such as ischemia-reperfusion injury (LIRI), non-alcoholic fatty disease (NAFLD), hepatocellular carcinoma (HCC). Therefore, controlling production is an attractive therapeutic strategy relation their treatment. In recent years, increasing evidence has supported effects polyphenols on via regulation levels. current review, we summarize polyphenols, quercetin, resveratrol, curcumin, during conditions induce injury, LIRI, NAFLD, HCC.

Language: Английский

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Targeting mTOR/YY1 signaling pathway by quercetin through CYP7A1-mediated cholesterol-to-bile acids conversion alleviated type 2 diabetes mellitus induced hepatic lipid accumulation

Phytomedicine, Journal Year: 2023, Volume and Issue: 113, P. 154703 - 154703

Published: Feb. 5, 2023

Language: Английский

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Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(11), P. 4999 - 5016

Published: July 25, 2023

Abstract Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity has extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, reactive oxygen species (ROS). Quercetin also demonstrated to exert a striking antiinflammatory effect mainly by inhibiting production cytokines, reducing expression cyclooxygenase lipoxygenase, preserving integrity mast cells. By regulating oxidative stress inflammation, which are regarded as two critical processes involved defense regular physiological operation biological systems, validated be effective treating variety disorders. Symptoms these reactions linked degenerative metabolic disorders, syndrome, cardiovascular, neurodegeneration, cancer, nonalcoholic fatty liver disease. Despite that evidence demonstrates antioxidants employed prevent excessive inflammatory processes, there still concerns regarding expense, accessibility, side agents. Notably, natural products, especially those derived from plants, widely accessible, affordable, generally safe. this review, abilities active ingredient application stress‐related disorders outlined detail.

Language: Английский

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SIRT1: Harnessing multiple pathways to hinder NAFLD

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107155 - 107155

Published: March 23, 2024

Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic disorders, with a high prevalence but no approved treatment. Therefore, it indispensable to find trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) strongly associated SIRT1 activation or overexpression attenuate NAFLD, while deficiency aggravates Besides, an array therapeutic agents, including natural compounds, synthetic traditional Chinese medicine formula, stem cell transplantation, alleviates NALFD via upregulation. Mechanically, NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, coordinating lipid metabolism, as well reducing hepatocyte apoptosis inflammation. In this review, we introduced structure function briefly, summarized effect on its mechanism, along application agonists in treating

Language: Английский

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