Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1199 - 1199

Published: June 18, 2022

Inflammation and oxidative stress are interlinked interdependent processes involved in many chronic diseases, including neurodegeneration, diabetes, cardiovascular cancer. Therefore, targeting inflammatory pathways may represent a potential therapeutic strategy. Emerging evidence indicates that phytochemicals extracted from edible plants have the to ameliorate disease phenotypes. In this scenario, ß-caryophyllene (BCP), bicyclic sesquiterpene, carnosic acid (CA), an ortho-diphenolic diterpene, were demonstrated exhibit anti-inflammatory, antioxidant activities, as well neuroprotective mitoprotective effects different vitro vivo models. BCP essentially promotes its by acting selective agonist allosteric modulator of cannabinoid type-2 receptor (CB2R). CA is pro-electrophilic compound that, response oxidation, converted electrophilic form. This can interact activate Keap1/Nrf2/ARE transcription pathway, triggering synthesis endogenous “phase 2” enzymes. However, given nature chemical structure, also exhibits direct effects. readily cross BBB accumulate brain regions, giving rise preventing mitochondrial dysfunction inhibiting activated microglia, substantially through activation pro-survival signalling pathways, regulation apoptosis autophagy, molecular mechanisms related quality control. Findings vitro/in experimental models Parkinson’s Alzheimer’s reported beneficial both compounds, suggesting their use treatments be promising strategy management neurodegenerative diseases aimed at maintaining homeostasis ameliorating glia-mediated neuroinflammation.

Language: Английский

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Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1448 - 1448

Published: June 19, 2022

Vascular dementia (VaD) is the second leading cause of dementia. The majority VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products receiving increasing attention for treatment neuroinflammatory diseases. aim this study was to investigate molecular pathways underlying protective effects fisetin, a flavonoid present in many fruits vegetables, mouse model induced repeated ischemia-reperfusion (IR) total bilateral carotid artery. Here, we found that brain injury, lipid peroxidation, neuronal death hippocampus, as well astrocyte microglial activation, reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, activation inflammasome components (NLRP-3, ASC, caspase 1), their downstream (IL-1β IL-18) release promote apoptotic cell death. Fisetin attenuated histological malondialdehyde levels, pathway apoptosis, increased expression, astrocyte, deficits. conclusion, fisetin could be due inhibition ROS-induced NF-κB/NLRP3 antioxidant Nrf2/HO-1, suggesting possible crosstalk between these pathways.

Language: Английский

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Sepsis-associated encephalopathy: From pathophysiology to clinical management

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110800 - 110800

Published: Aug. 22, 2023

Language: Английский

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Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5076 - 5076

Published: March 7, 2023

A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim this study was to evaluate beneficial effects fisetin, a naturally occurring polyphenol that frequently present in variety fruits vegetables. Uterine fragments were injected intraperitoneally cause endometriosis, fisetin given orally every day. At 14 days treatment, laparotomy performed, implants peritoneal fluids collected for histological, biochemical, molecular analyses. Rats subjected presented important macroscopic microscopic changes, increased mast cell (MC) infiltration, fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, volumes, well histological alterations, neutrophil cytokines release, number MCs together with expression chymase tryptase, diminished α smooth muscle actin (α-sma) transforming growth factor beta (TGF β) expressions. In addition, able reduce markers oxidative stress nitrotyrosine Poly ADP ribose expressions increase apoptosis lesions. conclusion, could represent new therapeutic strategy control perhaps targeting MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway stress.

Language: Английский

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ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Language: Английский

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Mitophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 10

Published: Jan. 27, 2022

Traumatic brain injury (TBI) contributes to death, and disability worldwide more than any other traumatic insult damage cellular components including mitochondria leads the impairment of functions function. In neurons, mitophagy, autophagy-mediated degradation damaged mitochondria, is a key process in quality control mitochondrial homeostasis energy supply plays fundamental role neuronal survival health. Conversely, defective mitophagy accumulation dysfunction, contributing inflammation, oxidative stress, cell death. Therefore, an extensive characterization mitophagy-related protective mechanisms, taking into account complex mechanisms by which each molecular player connected others, may provide rationale for development new therapeutic strategies TBI patients. Here, we discuss contribution TBI, underlying death highlight novel therapeutics based on newly discovered mitophagy-inducing strategies.

Language: Английский

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Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials

Oxidative Medicine and Cellular Longevity, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 15

Published: Feb. 17, 2023

Traumatic brain injury (TBI), a kind of external trauma-induced function alteration, has posed financial burden on the public health system. TBI pathogenesis involves complicated set events, including primary and secondary injuries that can cause mitochondrial damage. Mitophagy, process in which defective mitochondria are specifically degraded, segregates degrades allowing healthier network. Mitophagy ensures remain healthy during TBI, determining whether neurons live or die. acts as critical regulator maintaining neuronal survival healthy. This review will discuss pathophysiology consequences damage it causes to mitochondria. article explore mitophagy process, its key factors, pathways reveal role TBI. be further recognized therapeutic approach offer new insights into mitophagy’s progression.

Language: Английский

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Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Feb. 23, 2023

Sepsis-associated encephalopathy (SAE) is one of the most common types organ dysfunction without overt central nervous system (CNS) infection. It associated with higher mortality, low quality life, and long-term neurological sequelae, its mortality in patients diagnosed sepsis, progressing to SAE, 9% 76%. The pathophysiology SAE still unknown, but mechanisms are well elaborated, including oxidative stress, increased cytokines proinflammatory factors levels, disturbances cerebral circulation, changes blood-brain barrier permeability, injury brain's vascular endothelium, altered levels neurotransmitters, amino acid microvascular cells, mitochondria dysfunction, activation microglia astrocytes, neuronal death. diagnosis involves excluding direct CNS infection or other encephalopathies, which might hinder early detection appropriate implementation management protocols, especially paediatric where only a few cases have been reported literature. commonly applied diagnostic tools include electroencephalography, imaging, biomarker detection. treatment mainly focuses on managing underlying conditions using antibiotics supportive therapy. In contrast, sedative medication used judiciously treat those showing features such as agitation. widely dexmedetomidine neuroprotective by inhibiting apoptosis reducing sepsis-associated inflammatory response, resulting improved short-term shorter time ventilator. Other agents, dexamethasone, melatonin, magnesium, also being explored vivo ex encouraging results. Managing modifiable crucial improving generalised outcomes. From mentioned above, there experimentation models strategies. Extrapolation adult challenging because evolving brain technical complexity model investigated. Here, we reviewed current understanding pathophysiological mechanisms, methods, therapeutic interventions, potential emerging agents.

Language: Английский

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Nutrition and autophagy deficiency in critical illness

Current Opinion in Critical Care, Journal Year: 2023, Volume and Issue: 29(4), P. 306 - 314

Published: June 8, 2023

Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to high risk multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. discusses insight into role autophagy in involvement artificial feeding insufficient activation Recent findings Animal studies manipulating have shown its protective effects against kidney, lung, liver, intestinal injury after several insults. also protected peripheral, respiratory, cardiac muscle despite aggravated atrophy. Its acute brain is more equivocal. patient showed that suppressed illness, particularly protein/amino acid doses. Feeding-suppressed may explain short long-term harm by early enhanced calorie/protein large randomized controlled trials. Summary Insufficient at least partly explained feeding-induced suppression. why nutrition failed benefit critically ill patients or even induced harm. Safe, specific avoiding prolonged starvation opens perspectives for improving outcomes

Language: Английский

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The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(11), P. 6383 - 6394

Published: July 15, 2023

Language: Английский

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