CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in prefrontal cortex microglia in mice

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 110, P. 60 - 79

Published: Feb. 6, 2023

Chronic alcohol exposure (CAE) during late adolescence increases the risk of anxiety development. Alcohol-induced prefrontal cortex (PFC) microglial activation, characterized by morphological changes and increased associations with neurons, plays a critical role in pathogenesis anxiety. Alcohol NLRP3 inflammasome expression, increasing cytokine secretion activated microglia. Cannabinoid type 2 receptor (CB2R), an essential endocannabinoid system, regulates activation neuroinflammatory reactions. We aimed to investigate CB2R ameliorating adolescent CAE-induced anxiety-like behaviors C57BL/6J mice.Six-week-old mice were acclimated for 7 days then administered gavage (4 g/kg, 25 % w/v) 28 days. The intraperitoneally injected specific agonist AM1241 1 h before treatment. Anxiety-like withdrawal assessed open field test elevated plus maze 24 after last administration. Microglial microglia-neuron interactions, inflammasome-related molecule expression PFC measured using immunofluorescence, immunohistochemical, qPCR, Western blotting assays. morphology was evaluated Sholl analysis cell body-to-total size index. Additionally, N9 microglia LPS vitro, effects on investigated.After CAE, exhibited severe withdrawal. CAE induced obvious associations, markers, CB2R, molecules PFC. Microglia also showed marked filament retraction reduction body enlargement CAE. treatment ameliorated model mice, it prevented changes, reduced marker suppressed proinflammatory LPS-induced increase molecules, IL-1β release, M1 phenotype markers (iNOS CD86) cell, which reversed antagonist treatment.CAE caused at least partly inducing these preventing suppressing

Language: Английский

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Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress

Drug Delivery and Translational Research, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 7, 2023

Language: Английский

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Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action

Molecules, Journal Year: 2023, Volume and Issue: 28(5), P. 2306 - 2306

Published: March 2, 2023

Carnosic acid is a diterpenoid abundantly present in plants belonging to the genus Rosmarinus and Salvia of family Lamiaceae, accounting for their application traditional medicine. The diverse biological properties carnosic that include antioxidant, anti-inflammatory, anticarcinogenic activities have instigated studies on its mechanistic role, providing further insights into potential as therapeutic agent. Accumulating evidence has established relevance neuroprotective agent exhibiting efficacy combatting neuronal-injury-induced disorders. physiological importance mitigation neurodegenerative disorders just beginning be understood. This review summarizes current data mode action through which exerts role may serve strategize novel approaches these debilitating

Language: Английский

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RAGE Inhibitors in Neurodegenerative Diseases

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1131 - 1131

Published: April 9, 2023

Nonenzymatic reactions of reducing sugars with primary amino groups acids, proteins, and nucleic followed by oxidative degradations would lead to the formation advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading onset neurological disorders. interaction receptors for (RAGE) contribute activation intracellular signaling expression pro-inflammatory transcription factors various inflammatory cytokines. This cascade is associated diseases, including Alzheimer’s disease (AD), secondary traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), diabetic neuropathy, other AGE-related diabetes atherosclerosis. Furthermore, imbalance gut microbiota intestinal inflammation are also endothelial dysfunction, disrupted blood–brain barrier (BBB) thereby progression AD diseases. RAGE play an important role in altering composition increase permeability affect modulation immune-related inhibition AGE–RAGE interactions, through small molecule-based therapeutics, prevents events attenuates progression. Some antagonists, such as Azeliragon, currently clinical development treating AD, although there have been no FDA-approved therapeutics based antagonists. review outlines interactions a cause diseases current efforts developing

Language: Английский

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Carnosic acid protects against doxorubicin-induced cardiotoxicity through enhancing the Nrf2/HO-1 pathway

Food & Function, Journal Year: 2023, Volume and Issue: 14(8), P. 3849 - 3862

Published: Jan. 1, 2023

Doxorubicin (DOX) is used extensively in anticancer therapy, but its clinical application limited due to cardiotoxicity. Carnosic acid (CA) a bioactive compound found rosemary. It has been shown reduce inflammation and reactive oxygen species. The purpose of this study was investigate the potential cardioprotective effects CA response DOX-induced Here, C57BL/6 mice were administered an intraperitoneal injection DOX (5 mg kg-1, ip) once week for three consecutive weeks treated with (40 ig) three-week experimental period. For vitro study, neonatal rat ventricular cardiomyocytes validate protective (20 μM) markedly suppressed oxidative stress, apoptosis, pyroptosis responses mouse hearts, eventually improving cardiac function. showed antioxidant effect by activating nuclear factor erythroid 2-related (Nrf2) downstream heme oxygenase-1 (HO-1); also reduced stress lowering MDA lipid ROS levels raising SOD GSH-px levels. Additionally, treatment significantly increased Bcl-2 inhibited Bax Caspase-3 cleavage Moreover, NOD-like receptor protein 3 (NLRP3) pathway mitigate pyroptosis, as evidenced lowered caspase1, interleukin-18, interleukin-1β. Consistently, transfection Nrf2-siRNA eliminated on cardiomyocytes. Altogether, our findings demonstrated that NLRP3 inflammasomes via Nrf2-related cytoprotective system protected heart from damage, implying use could be therapeutic strategy prevention DOX-associated myocardiopathy.

Language: Английский

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Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3203 - 3203

Published: March 11, 2024

Mental disorders account for one of the most prevalent categories burden disease worldwide, with depression expected to be largest contributor by 2030, closely followed anxiety. The COVID-19 pandemic possibly exacerbated these challenges, especially amongst adolescents, who experienced isolation, disrupted routines, and limited healthcare access. Notably, has been associated long-term neurological effects known as “long-COVID”, characterized both cognitive psychopathological symptoms. In general, psychiatric disorders, including those related long-COVID, are supposed due widespread inflammation leading neuroinflammation. Recently, endocannabinoid system (ECS) emerged a potential target addressing anxiety pathophysiology. Specifically, natural or synthetic cannabinoids, able selectively interact cannabinoid type-2 receptor (CB2R), recently revealed new therapeutic in neuropsychiatric absent psychotropic activity. Among promising CB2R ligands, bicyclic sesquiterpene β-caryophyllene (BCP) an excellent anti-inflammatory antioxidant agent. This review underscores BCP’s immunomodulatory properties, highlighting its management

Language: Английский

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Rosmarinus officinalis Linn.: unveiling its multifaceted nature in nutrition, diverse applications, and advanced extraction methods

Journal of Umm Al-Qura University for Applied Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: April 3, 2024

Abstract Rosemary ( Rosmarinus officinalis Linn. or Salvia rosmarinus Spenn. ) is an aromatic herb renowned for its culinary, medicinal, and industrial significance. This review offers a multifaceted exploration of rosemary, delving into nutritional composition, traditional culinary applications, historical uses in medicine. The extends to cosmetic pharmaceutical elucidating rosemary’s role as natural preservative integration cosmeceutical formulations. Extraction methods, both classical contemporary, are critically examined, with emphasis on recent sustainable approaches their impact bioactive compounds. work concludes forward-looking perspective, discussing innovative extraction techniques, advanced technologies, the potential commercial viability rosemary-related industries. comprehensive serves valuable resource, offering insights diverse dimensions from applications cutting-edge advancements science.

Language: Английский

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Pivotal role of AGE-RAGE axis in brain aging with current interventions

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102429 - 102429

Published: July 18, 2024

Language: Английский

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Harnessing Cannabis sativa Oil for Enhanced Skin Wound Healing: The Role of Reactive Oxygen Species Regulation

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(10), P. 1277 - 1277

Published: Sept. 30, 2024

emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil reducing reactive oxygen species (ROS) during healing acute and chronic wounds, comparing it to standard treatments. ROS, produced from various internal external sources, play crucial role development by causing cell tissue damage. Understanding ROS on skin wounds is essential, they act both signaling molecules contributors oxidative Cannabis oil, recognized antioxidant properties, may help mitigate damage scavenging upregulating antioxidative mechanisms, potentially enhancing emphasizes ongoing research future potential dermatological treatments, highlighted through clinical studies patent updates. Despite promising benefits, optimizing formulations therapeutic applications remains challenge, underscoring need further realize capabilities wounds.

Language: Английский

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An enriched environment ameliorates maternal sleep deprivation-induced cognitive impairment in aged mice by improving mitochondrial function via the Sirt1/PGC-1α pathway

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Background: Early life stress can cause cognitive impairment in aged offspring. Environmental enrichment (EE) is considered to be an effective non-pharmacological treatment for improving decline. The aim of this research was evaluate the effect EE, on offspring induced by maternal sleep deprivation (MSD) and underlying mechanisms involved investigate its potential value clinical practice. Methods: CD-1 damns were subjected or not during late gestation. Twenty-one days after birth, assigned standard EE cages. At 18 months-old, learning memory function mice evaluated using Morris water maze. hippocampal prefrontal cortical levels protein, gene, proinflammation cytokines, oxidative indicators examined Western blot, real-time polymerase chain reaction, enzyme linked immunosorbent assay, biochemical assays. Results: Offspring MSD group exhibited declined abilities compared with control animals. Moreover, Sirtuin1 (Sirt1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), postsynaptic density protein-95, synaptophysin lower those cytokines higher group; meanwhile, superoxide dismutase content malondialdehyde reactive oxygen species contents lower. However, these deleterious changes ameliorated exposure EE. Conclusions: attenuates MSD-induced impairment, stress, neuroinflammation reverses reduction synaptic protein via Sirt1/PGC-1α pathway.

Language: Английский

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