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

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 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.

Язык: Английский

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7910 - 7910

Опубликована: Апрель 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Язык: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Язык: Английский

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The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract Pediatric cancers are the driving cause of death for children and adolescents. Due to safety requirements considerations, treatment strategies drugs pediatric have been so far scarcely studied. It is well known that tumor cells tend progressively evade cell pathways, which as apoptosis resistance, one hallmarks cancer, dominating drug resistance. Recently, treatments targeting nonapoptotic drawn great attention. Pyroptosis, a newly specialized form death, acts critical physiological regulator in inflammatory reaction, development, tissue homeostasis stress response. The action different forms pyroptosis significance therapy cancers. Pyroptosis could be induced consequently modulate tumorigenesis, progression, metastasis if treated with local or systemic therapies. However, excessive uncontrolled might lead damage, acute inflammation, even cytokine release syndrome, facilitates progression recurrence. Herein, we aimed describe molecular mechanisms pyroptosis, highlight discuss challenges opportunities activating pathways through various oncologic therapies multiple neoplasms, including osteosarcoma, neuroblastoma, leukemia, lymphoma, brain tumors.

Язык: Английский

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Apoptosis, necroptosis, and pyroptosis as alternative cell death pathways induced by chemotherapeutic agents?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(6), С. 189024 - 189024

Опубликована: Ноя. 1, 2023

For decades, common chemotherapeutic drugs have been established to trigger apoptosis, the preferred immunologically "silent" form of cell death. The primary objective this review was show that various FDA-approved drugs, including cisplatin, cyclosporine, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, paclitaxel, or vinblastine can necroptosis and pyroptosis. We aimed provide advantages disadvantages induction given type death by chemotherapeutical agents. Moreover, we give a short overview molecular mechanism each indicate existing crosstalks between types. Finally, comparison types facilitate exploration induced other Understanding pathway drug lessen side effects assist discovery new combinations with synergistic low systemic toxicity.

Язык: Английский

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The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Март 23, 2023

Glutamate plays an important role in excitotoxicity and ferroptosis. Excitotoxicity occurs through over-stimulation of glutamate receptors, specifically NMDAR, while the non-receptor-mediated pathway, high concentrations reduce cystine uptake by inhibiting System Xc-, leading to intracellular glutathione depletion resulting ROS accumulation, which contributes increased lipid peroxidation, mitochondrial damage, ultimately Oxidative stress appears crosstalk between ferroptosis, it is essential maintain homeostasis inhibit oxidative responses vivo . As researchers work develop natural compounds further investigate complex mechanisms regulatory functions ferroptosis excitotoxicity, new avenues will be available for effective treatment ischaemic stroke. Therefore, this paper provides a review molecular glutamate-mediated

Язык: Английский

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Role of pyroptosis in the pathogenesis and treatment of diseases

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Апрель 25, 2023

Abstract Programmed cell death (PCD) is regarded as a pathological form of with an intracellular program mediated, which plays pivotal role in maintaining homeostasis and embryonic development. Pyroptosis new paradigm PCD, has received increasing attention due to its close association immunity disease. inflammatory mediated by gasdermin that promotes the release proinflammatory cytokines contents induced inflammasome activation. Recently, evidence studies shows pyroptosis crucial conditions like cardiovascular diseases (CVDs), cancer, neurological (NDs), metabolic (MDs), suggesting targeting potential intervention for treatment these diseases. Based on this, review aims identify molecular mechanisms signaling pathways related activation summarizes current insights into complicated relationship between multiple human (CVDs, NDs, MDs). We also discuss promising novel strategy method treating focus pathway application clinics.

Язык: Английский

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Pyroptosis as a double-edged sword: The pathogenic and therapeutic roles in inflammatory diseases and cancers

Life Sciences, Год журнала: 2023, Номер 318, С. 121498 - 121498

Опубликована: Фев. 11, 2023

Язык: Английский

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HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation

Translational Stroke Research, Год журнала: 2024, Номер unknown

Опубликована: Май 14, 2024

Abstract Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration rtPA essential for restoring perfusion acute ischemic stroke, though it concurrently elevates the risk hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player neuroinflammation after brain ischemia ischemia–reperfusion. Released passively necrotic cells actively secreted, including direct secretion HMGB1 into extracellular space packaging intracellular vesicles immune cells, glial platelets, endothelial represents prototypical damage-associated molecular pattern (DAMP). It intricately involved pathogenesis atherosclerosis, thromboembolism, detrimental inflammation during early phases stroke. Moreover, significantly contributes to neurovascular remodeling functional recovery later stages. Significantly, mediates transformation facilitating neuroinflammation, directly compromising integrity blood–brain barrier, enhancing MMP9 through interaction with rtPA. As systemic inflammatory factor, also implicated post-stroke depression an elevated stroke-associated pneumonia. role extends influencing polarizing various subtypes cells. This includes mediating excitotoxicity due excitatory amino acids, autophagy, release, NET formation, autocrine trophic pathways. Given multifaceted role, recognized crucial therapeutic target prognostic marker stroke In this review, we summarize structure redox properties, pathways, regulation cell activity, pathophysiological mechanisms hemorrhage HMGB1, which will pave way developing new neuroprotective drugs, reduction expansion thrombolysis time window.

Язык: Английский

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Endoplasmic reticulum stress-mediated cell death in cardiovascular disease

Cell Stress and Chaperones, Год журнала: 2024, Номер 29(1), С. 158 - 174

Опубликована: Янв. 29, 2024

The endoplasmic reticulum (ER) plays a vital function in maintaining cellular homeostasis. Endoplasmic stress (ERS) can trigger various modes of cell death by activating the unfolded protein response (UPR) signaling pathway. Cell crucial role occurrence and development diseases such as cancer, liver diseases, neurological cardiovascular diseases. Several including hypertension, atherosclerosis, heart failure are associated with ER stress. stress-mediated is interest disease. Moreover, an increasing body evidence supports potential modulating ERS for treating This paper provides comprehensive review UPR pathway, mechanisms that induce death, Additionally, we discuss common along therapeutic strategies.

Язык: Английский

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