Therapeutic potential of natural molecules against Alzheimer's disease via SIRT1 modulation

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114474 - 114474

Published: March 4, 2023

Alzheimer's disease (AD) is a neurodegenerative mainly characterized by progressive cognitive dysfunction and memory impairment. Recent studies have shown that regulating silent information regulator 1 (SIRT1) expression has significant neuroprotective effect, SIRT1 may become new therapeutic target for AD. Natural molecules are an important source of drug development use in AD therapy regulate wide range biological events as well other SIRT1-mediated signaling pathways. This review aims to summarize the correlation between identify vivo vitro investigating anti-AD properties natural modulators A literature search was conducted published January 2000 October 2022 using various databases, including Web Science, PubMed, Google Scholar, Science Direct, EMBASE. molecules, such resveratrol, quercetin, icariin, bisdemethoxycurcumin, dihydromyricetin, salidroside, patchouli, sesamin, rhein, ligustilide, tetramethoxyflavanone, 1-theanine, schisandrin, curcumin, betaine, pterostilbene, ampelopsin, schisanhenol, eriodictyol, potential modulate pathways, thereby combating The modulating discussed this provide potentially novel multi-mechanistic strategy However, future clinical trials need be further investigate their beneficial determine safety efficacy activators against

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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Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(7), P. 6868 - 6884

Published: July 2, 2024

The onset of neurodegenerative diseases involves a complex interplay pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between stress autophagy in disorders, highlighting as pivotal disease pathogenesis. Reactive oxygen species (ROS) play dual roles cellular homeostasis regulation, with disruptions redox signaling contributing to neurodegeneration. activation Nrf2 pathway represents critical antioxidant mechanism, while maintains by degrading altered cell components. interaction among p62/SQSTM1, Nrf2, Keap1 forms regulatory essential for response, whose dysregulation leads aggregate accumulation. Targeting Nrf2-p62/SQSTM1 holds promise therapeutic intervention, mitigating preserving functions. Additionally, this explores potential synergy endocannabinoid system neuroprotection. Further research is needed elucidate involved molecular mechanisms develop effective strategies against

Language: Английский

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Sirtuin dysregulation in Parkinson's disease: Implications of acetylation and deacetylation processes

Life Sciences, Journal Year: 2024, Volume and Issue: 342, P. 122537 - 122537

Published: Feb. 29, 2024

Language: Английский

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Phytomedicine for neurodegenerative diseases: The road ahead

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(6), P. 2993 - 3019

Published: April 10, 2024

Abstract Neurodegenerative disorders (NDs) are among the most common causes of death across globe. NDs characterized by progressive damage to CNS neurons, leading defects in specific brain functions such as memory, cognition, and movement. The Parkinson's, Alzheimer's, Huntington's, amyotrophic lateral sclerosis (ALS). Despite extensive research, no therapeutics or medications against have been proven be effective. current treatment involving symptom‐based targeting disease pathogenesis has certain limitations, drug resistance, adverse side effects, poor blood–brain barrier permeability, bioavailability drugs. Some studies shown that plant‐derived natural compounds hold tremendous promise for treating preventing NDs. Therefore, primary objective this review article is critically analyze properties potency some studied phytomedicines, quercetin, curcumin, epigallocatechin gallate (EGCG), apigenin, cannabinoids, highlight their advantages limitations developing next‐generation alternative treatments Further research on pre‐clinical clinical plant‐based drugs from bench bedside warranted.

Language: Английский

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Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment

Life, Journal Year: 2024, Volume and Issue: 14(8), P. 991 - 991

Published: Aug. 9, 2024

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, burning pain in the upper lower extremities. The pathophysiology not completely understood; however, it believed that chemotherapies induce via directly damaging mitochondria, impairing function ion channels, triggering immunological mechanisms, disrupting microtubules. treatment medical challenge, there are no approved pharmacological options. Currently, duloxetine other antidepressants, antioxidant, anti-inflammatory, ion-channel targeted therapies commonly used clinics to relieve symptoms CIPN. Several types such as cannabinoids, sigma−1 receptor antagonists, nicotinamides ribose, being evaluated preclinical clinical studies. This paper summarizes information related physiology medicines could be for treating this condition.

Language: Английский

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Cannabinoids and Sleep: Exploring Biological Mechanisms and Therapeutic Potentials

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3603 - 3603

Published: March 22, 2024

The endogenous cannabinoid system (ECS) plays a critical role in the regulation of various physiological functions, including sleep, mood, and neuroinflammation. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinomimimetics, some N-acylethanolamides, particularly palmitoyethanolamide, have emerged potential therapeutic agents for management sleep disorders. THC, psychoactive component cannabis, may initially promote but, long term, alters architecture, while CBD shows promise improving quality without effects. Clinical studies suggest that modulates endocannabinoid signaling through several receptor sites, offering multifaceted approach to regulation. Similarly, palmitoylethanolamide (PEA), addition interacting with system, acts an agonist on peroxisome proliferator-activated receptors (PPARs). favorable safety profile PEA long-term use make them attractive alternative conventional pharmacotherapy. integration latter two compounds into comprehensive treatment strategies, together cognitive–behavioral therapy insomnia (CBT-I), represents holistic address multifactorial nature Further research is needed establish optimal dosage, safety, efficacy different patient populations, but offers hope improved general well-being.

Language: Английский

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Therapeutic Potential of Cannabinoids in Glaucoma

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(8), P. 1149 - 1149

Published: Aug. 14, 2023

Glaucoma is a leading cause of irreversible blindness worldwide. To date, intraocular pressure (IOP) the only modifiable risk factor in glaucoma treatment, but even treated patients, disease can progress. Cannabinoids, which have been known to lower IOP since 1970s, shown beneficial effects patients beyond their IOP-lowering properties. In addition classical cannabinoid receptors CB1 and CB2, knowledge non-classical endocannabinoid system has increased recent years. particular, CB2 receptor mediate anti-inflammatory, anti-apoptotic, neuroprotective properties, may represent promising therapeutic target for neuroprotection patients. Due vasodilatory effects, cannabinoids improve blood flow optic nerve head, suggest vasoprotective potential counteract altered observed The aim this review was assess available evidence on pharmacological mechanisms underlying IOP, neuroprotection, ocular hemodynamics discussed.

Language: Английский

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Cannabinoid CB2 Receptors in Neurodegenerative Proteinopathies: New Insights and Therapeutic Potential

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3000 - 3000

Published: Nov. 22, 2022

Some of the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, are proteinopathies characterized by accumulation specific protein aggregates in brain. Such misfolded can trigger modulation innate adaptive immune systems subsequently lead to chronic neuroinflammation that drives onset progression diseases. Since there is still no effective disease-modifying treatment, new therapeutic targets for have been sought. The endocannabinoid system, particular cannabinoid CB2 receptors, extensively studied, due their important role neuroinflammation, especially microglial cells. Several studies shown promising effects receptor activation on reducing aggregation-based pathology as well attenuating inflammation several dementia-related symptoms. In this review, we discuss available data receptors potential benefits limitations agonists these therapy proteinopathies.

Language: Английский

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Cannabinoids as Promising Inhibitors of HER2-Tyrosine Kinase: A Novel Strategy for Targeting HER2-Positive Ovarian Cancer

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 6191 - 6200

Published: Feb. 8, 2025

Human epidermal growth factor receptor 2 (HER2) is a transmembrane within the ErbB family that plays pivotal role in progression of various aggressive cancers. HER2-positive tumors often develop resistance to standard therapies, necessitating exploration innovative treatment options. Cannabinoids, bioactive compounds from Cannabis sativa such as cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), have gained attention for their potential anticancer properties. This study evaluates efficacy CBD, CBG, CBN targeting ovarian cancer through kinase inhibition assays, surface plasmon resonance (SPR), molecular docking, cell viability assessments. SPR analysis revealed cannabinoids bind strongly HER2-tyrosine (HER2-TK), with CBD showing highest affinity (K D = 6.16 μM), significantly better than afatinib 26.30 CBG demonstrating moderate 17.07 μM). In was most potent inhibitor (IC50 24.7 nM), followed by 38 suggesting ability disrupt HER2-mediated signaling pathways. Molecular docking studies highlighted critical interactions between essential HER2 residues (Leu796, Thr862, Asp863). effectively inhibited SKOV3 cells 13.8 μM 16.6 μM, respectively), comparable traditional tyrosine inhibitors. These findings underscore therapeutic cannabinoids, particularly alternative or adjunct therapies cancers, promise mitigating adverse effects associated existing treatments.

Language: Английский

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