The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6328 - 6328

Published: March 28, 2023

Neuroinflammation is a critical factor in developing and progressing numerous brain diseases, including neurodegenerative diseases. Chronic or excessive neuroinflammation can lead to neurotoxicity, causing damage contributing the onset progression of various Therefore, understanding mechanisms strategies control them crucial for treating Studies have shown that plays vital role such as Alzheimer's (AD) Parkinson's (PD), stroke. Additionally, effects PM

Language: Английский

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Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3755 - 3755

Published: Feb. 13, 2023

As the greatest defense organ of body, skin is exposed to endogenous and external stressors that produce reactive oxygen species (ROS). When antioxidant system body fails eliminate ROS, oxidative stress initiated, which results in cellular senescence, inflammation, cancer. Two main possible mechanisms underlie stress-induced One mechanism ROS directly degrade biological macromolecules, including proteins, DNA, lipids, are essential for cell metabolism, survival, genetics. Another one mediate signaling pathways, such as MAPK, JAK/STAT, PI3K/AKT/mTOR, NF-κB, Nrf2, SIRT1/FOXO, affecting cytokine release enzyme expression. natural antioxidants, plant polyphenols safe exhibit a therapeutic potential. We here discuss detail potential selected polyphenolic compounds outline relevant molecular targets. Polyphenols study according their structural classification include curcumin, catechins, resveratrol, quercetin, ellagic acid, procyanidins. Finally, latest delivery (taking curcumin an example) current status clinical research summarized, providing theoretical foundation future generation new pharmaceuticals cosmetics.

Language: Английский

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Alzheimer’s Disease: Novel Targets and Investigational Drugs for Disease Modification

Drugs, Journal Year: 2023, Volume and Issue: 83(15), P. 1387 - 1408

Published: Sept. 20, 2023

Novel agents addressing non-amyloid, non-tau targets in Alzheimer's Disease (AD) comprise 70% of the AD drug development pipeline currently clinical trials. Most target processes identified Common Research Ontology (CADRO) are represented by novel Inflammation and synaptic plasticity/neuroprotection CADRO categories with largest number candidate therapies. Within these categories, there few overlapping among test agents. Additional being evaluated include apolipoprotein E $$\varepsilon$$ 4 (APOE4) effects, lipids lipoprotein receptors, neurogenesis, oxidative stress, bioenergetics metabolism, vascular factors, cell death, growth factors hormones, circadian rhythm, epigenetic regulators. We highlight current drugs tested within their mechanisms. Trials will be informative regarding which can modulated to produce a slowing decline. Possible therapeutic combinations may suggested trial outcomes. Biomarkers evolving concert new agents, biomarker outcomes offer means supporting disease modification putative treatment. Identification corresponding therapeutics an important advancing treatments for AD.

Language: Английский

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β-Nicotinamide mononucleotide activates NAD+/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102745 - 102745

Published: May 13, 2023

Sepsis-associated encephalopathy (SAE) is one of the common serious complications in sepsis, and pathogenesis SAE remains unclear. Sirtuin 1 (SIRT1) has been reported to be downregulated hippocampus SIRT1 agonists can attenuated cognitive dysfunction septic mice. Nicotinamide adenine dinucleotide (NAD+) a key substrate maintain deacetylation activity SIRT1. As an intermediate NAD+, β-Nicotinamide Mononucleotide (NMN) promising treating neurodegenerative diseases cerebral ischemic injury. Thus we sought investigate potential role NMN treatment. The model was established by cecal ligation puncture (CLP) vivo, neuroinflammation with LPS-treated BV-2 cells vitro. Memory impairment assessed Morris water maze fear conditioning tests. result, levels PGC-1α were significantly reduced mice, while acetylation total lysine, phosphorylation P38 P65 enhanced. All these changes induced sepsis inverted NMN. Treating resulted improved behavior performance tests maze. Apoptosis, inflammatory oxidative responses mice after administration. These protective effect against memory dysfunction, injuries reversed inhibitor, EX-527. Similarly, LPS-induced activation NMN, EX-527 or knockdown could reverse such In conclusion, sepsis-induced region NAD+/SIRT1 pathway might involved mechanisms effect.

Language: Английский

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Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan

Pharmacological Research, Journal Year: 2023, Volume and Issue: 188, P. 106676 - 106676

Published: Jan. 21, 2023

Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains be elucidated. Here, wild-type mice Zmpste24-/- progeroid were used investigate genistein lifespan mammals. A series longitudinal, clinically relevant measurements performed evaluate effect healthspan. It was found that dietary promoted a healthier longer life associated with decrease levels systemic inflammatory cytokines mice. Furthermore, ameliorated dysfunctions, such as intestinal inflammation, leaky gut, impaired epithelial regeneration. distinct genistein-mediated alteration microbiota observed by increasing Lachnospira abundance short-chain fatty acid (SCFA) production. Further fecal transplantation dirty cage sharing experiments indicated from genistein-fed rejuvenated extended demonstrated genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced organoid damage. Moreover, propionate regulatory T cell-derived interleukin 10 production, which macrophage-derived inflammation. This study provided first data, authors' knowledge, indicating modulates extends healthspan existence link between provides rationale for interventions against age-associated frailty.

Language: Английский

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Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 1, 2023

Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis ovarian tissue. When the balance between ROS antioxidants is disrupted, however, it can cause serious consequences oxidative stress (OS), quantity quality oocytes will decline. Therefore, this review discusses interrelationship OS premature insufficiency (POI), potential mechanisms methods by which improve POI through controlling level OS. We found that mediate changes genetic materials, signal pathways, transcription factors microenvironment, resulting abnormal apoptosis granulosa cells (GCs) meiosis as well decreased mitochondrial Deoxyribonucleic Acid(mtDNA) other changes, thus accelerating process aging. However, antioxidants, mesenchymal stem (MSCs), biological enzymes delay disease reducing vivo .

Language: Английский

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Natural Phytochemicals as SIRT Activators—Focus on Potential Biochemical Mechanisms

Nutrients, Journal Year: 2023, Volume and Issue: 15(16), P. 3578 - 3578

Published: Aug. 14, 2023

Sirtuins are a family of proteins with enzymatic activity. There seven mammalian sirtuins (SIRT1-SIRT7) that found in different cellular compartments. They part crucial pathways and regulated by many factors, such as chemicals, environmental stress, phytochemicals. Several vitro vivo studies have presented their involvement anti-inflammatory, antioxidant, antiapoptotic processes. Recent findings imply phytochemicals resveratrol, curcumin, quercetin, fisetin, berberine, kaempferol may regulate the activity sirtuins. Resveratrol mainly activates SIRT1 indirectly AMPK. Curcumin influences SIRT3, but its is broad, cells affected. Quercetin modulates SIRT1, which triggers antioxidant responses. Fisetin, through regulation, modifies lipid metabolism anti-inflammatory Berberine has wide spectrum effects significant impact on signaling pathways. Finally, induction. This review aims to summarize recent properties modulation sirtuin activity, particular focus biochemical aspects.

Language: Английский

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Nrf2: a dark horse in doxorubicin-induced cardiotoxicity

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 26, 2023

Abstract Being a broad-spectrum anticancer drug, doxorubicin is indispensable for clinical treatment. Unexpectedly, its cardiotoxic side effects have proven to be formidable obstacle. Numerous studies are currently devoted elucidating the pathological mechanisms underlying doxorubicin-induced cardiotoxicity. Nrf2 has always played crucial role in oxidative stress, but numerous demonstrated that it also plays vital part like cell death and inflammation. on associated with cardiotoxicity demonstrate this. Several drugs, natural synthetic compounds, as well small molecule RNAs been prevent by activating Nrf2. Consequently, this study emphasizes introduction of Nrf2, discusses cardiotoxicity, concludes summary therapeutic modalities targeting ameliorate highlighting potential value

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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Endothelial dysfunction: molecular mechanisms and clinical implications

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 22, 2024

Abstract Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays crucial role in the initiation progression CVD, serving as pivotal factor pathogenesis cardiovascular, metabolic, other related diseases. The regulation endothelial is influenced by various risk factors intricate signaling pathways, which vary depending on specific context. Despite numerous research efforts aimed at elucidating mechanisms underlying dysfunction, precise molecular pathways involved remain incompletely understood. This review elucidates recent findings pathophysiological including nitric oxide availability, oxidative stress, inflammation‐mediated pathways. We also discuss impact pathological conditions, atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, neurodegenerative Furthermore, we summarize traditional novel potential biomarkers well pharmacological nonpharmacological therapeutic strategies for protection treatment CVD complications. Consequently, this to improve understanding emerging approaches reducing developing associated complications, mitigating dysfunction.

Language: Английский

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