Oxidative Stress, Plant Natural Antioxidants, and Obesity

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(4), P. 1786 - 1786

Published: Feb. 11, 2021

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors mitochondrial activity, modifying concentration inflammation mediators associated with a large number and size adipocytes, promoting lipogenesis, stimulating differentiation preadipocytes to mature regulating energy balance hypothalamic neurons that control appetite. This review discusses participation oxidative obesity groups compounds found plants antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, isoflavones), curcuminoids (b) carotenoids, (c) capsaicinoids casinoids, (d) isothiocyanates, (e) catechins, (f) vitamins. Examples are analyzed, resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, garlic. The activities these depend on their reactive oxygen species (ROS) scavengers capacity prevent activation NF-κB (nuclear factor κ-light-chain-enhancer activated B cells), reduce expression target genes, including those participating inflammation. We conclude natural have therapeutic potential for diseases mediated by stress, particularly obesity. Controlled well-designed clinical trials still necessary better know effects compounds.

Language: Английский

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The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(1), P. 50 - 75

Published: May 20, 2021

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction cytokines, primarily type I interferons. Recently, aberrant and deranged cGAS-STING axis is closely implicated multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver aortic aneurysm dissection, obesity, etc. This because massive loads damage-associated molecular patterns (mitochondrial DNA, DNA extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles tissues, which are sensed by pathway. Also, pathway crosstalk with intracellular homeostasis processes like apoptosis, autophagy, regulate metabolism. Targeting derailed STING has become necessary for chronic diseases. Meanwhile, excessive interferons impact on cardiovascular health remain entirely elusive. In this review, we summarize intimate connection between disorders. We also discuss some potential small molecule inhibitors review provides insight stimulate interest support future research into understanding tissues

Language: Английский

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Mitophagy in Human Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 3903 - 3903

Published: April 9, 2021

Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and fundamental in highly differentiated post-mitotic cells are dependent on aerobic metabolism, such as neurons, muscle cells, hepatocytes. Both defective excessive mitophagy have been proposed to contribute age-related neurodegenerative diseases, Parkinson’s Alzheimer’s metabolic vascular complications of diabetes, myocardial injury, dystrophy, liver disease, among others. Pharmacological or dietary interventions restore homeostasis facilitate the elimination irreversibly damaged mitochondria, thus, could serve potential therapies several chronic diseases. However, despite extraordinary advances this field, mainly derived from vitro preclinical animal models, human applications based regulation mitochondrial quality patients not yet approved. In review, we summarize key autophagy pathways their prevalent diseases highlight use specific interventions.

Language: Английский

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Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13033 - 13033

Published: Aug. 22, 2023

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death neurons, leading to range neurological symptoms. Despite heterogeneity these conditions, common denominator is implication mitochondrial dysfunction in their pathogenesis. Mitochondria play crucial role creating biomolecules, providing energy through adenosine triphosphate (ATP) generated oxidative phosphorylation (OXPHOS), producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented losing membrane potential, they contribute diseases. In this review, we explore how mitochondria fuse undergo fission, especially context NDs. We discuss genetic protein mutations linked impact dynamics. also look at key regulatory proteins fusion (MFN1, MFN2, OPA1) fission (DRP1 FIS1), including post-translational modifications. Furthermore, highlight potential drugs that can influence By unpacking complex processes, aim direct research towards treatments improve life quality for people with challenging conditions.

Language: Английский

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cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 9, 2024

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.

Language: Английский

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The Metabolic Syndrome, a Human Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2251 - 2251

Published: Feb. 13, 2024

This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy associated diseases/disorders, or just related rather independent pathologies. The human nature MS (its exceptionality in Nature and its close interdependence with action evolution) is presented discussed. text also describes components, special emphasis description their interrelations (including syndromic development recruitment), as well consequences upon energy handling partition. main theories MS’s origin are relation to hepatic steatosis, type 2 diabetes, obesity, encompass most components described so far. differential effects sex biological considered under light social needs evolution, which directly epidemiology, severity, relations senescence. triggering maintenance factors discussed, especial inflammation, complex process affecting different levels organization critical element for development. Inflammation operation connective tissue adipose organ) widely studied acknowledged influence diet. role diet composition, including transcendence anaplerotic Krebs cycle from dietary amino acid supply (and timing), developed context testosterone β-estradiol control insulin-glycaemia core system carbohydrate-triacylglycerol handling. high probability acting unique (essentially monophyletic) presented, together additional perspectives/considerations treatment this ‘very’ disease.

Language: Английский

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Mitochondrial quality surveillance as a therapeutic target in myocardial infarction

Acta Physiologica, Journal Year: 2020, Volume and Issue: 231(3)

Published: Dec. 3, 2020

Abstract Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. As mitochondrial dysfunction critically contributes to the pathogenesis MI, intensive research focused on development therapeutic strategies targeting homeostasis. Mitochondria possess quality control system which maintains restores their structure function by regulating fission, fusion, biogenesis, degradation death. In response slight damage such as transient hypoxia or mild oxidative stress, metabolism shifts from phosphorylation glycolysis, in order reduce oxygen consumption maintain ATP output. Mitochondrial dynamics are also activated modify shape structure, meet cardiomyocyte energy requirements through augmenting reducing mass. When damaged mitochondria cannot be repaired, poorly structured will degraded mitophagy, process often accompanied biogenesis. Once insult severe enough induce lethal cell, death pathway activation an inevitable consequence, apoptosis necrosis program initiated remove cells. surveillance hierarchical preserving defending cardiomyocytes against stress. A failure this has been regarded one potential pathologies underlying MI. review, we discuss recent findings focusing role highlight available approaches during

Language: Английский

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Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 11, 2020

Placental insufficiency and adipose tissue dysregulation are postulated to play key roles in the pathophysiology of both pre-eclampsia (PE) gestational diabetes mellitus (GDM). A dysfunctional release deleterious signalling motifs can offset an increase circulating oxidative stressors, proinflammatory factors various cytokines. It has been previously that endothelial dysfunction, instigated by from endocrine organs such as placenta tissue, may be a mediator vasculopathy is evident adverse obstetric complications. These pathways also have significant effects on long term maternal cardiometabolic health outcomes, specifically cardiovascular disease, hypertension, type II diabetes. Recent studies noted PE GDM strongly associated with lower flow-mediated dilation, however exact which link dysfunction clinical outcomes these complications remains question. The current diagnostic regimen for lacks specificity consistency relation guidelines. Furthermore, therapeutic options rely largely symptom control antihypertensives insulin therapy, rather than early intervention or prophylaxis. better understanding pathogenic origin will allow more targeted interventions. In this review we explore complex relationship between investigate how intricate affect function and, hence, role acute development future chronic outcomes.

Language: Английский

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Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(5), P. 1645 - 1645

Published: Feb. 28, 2020

The estrogen-related receptor alpha (ESRRA) is an orphan nuclear (NR) that significantly influences cellular metabolism. ESRRA predominantly expressed in metabolically-active tissues and regulates the transcription of metabolic genes, including those involved mitochondrial turnover autophagy. Although activity well-characterized several types cancer, recent reports suggest it also has important role diseases. This minireview focuses on regulation metabolism function by its potential as a target for treatment disorders.

Language: Английский

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Mitochondrial Transplantation as a Novel Therapeutic Strategy for Mitochondrial Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4793 - 4793

Published: April 30, 2021

Mitochondria are the major source of intercellular bioenergy in form ATP. They necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation metabolism apoptosis. Mitochondrial dysfunction has been observed variety diseases cardiovascular disease, aging, type 2 diabetes, cancer degenerative brain disease. In other words, interpretation mitochondrial signals potential to be applied a treatment various caused by disorders. recent years, transplantation increasingly topic interest an innovative strategy augmentation replacement mitochondria. this review, we focus on that associated with highlight studies related rescue tissue-specific We firmly believe is optimistic therapeutic approach finding potentially valuable diseases.

Language: Английский

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