Search Results (2,241)

Iridoids are compounds recognized for their neuroprotective properties and their potential application in the treatment of neurodegenerative diseases. Geniposide (GP) and asperuloside (ASP) are iridoids that have demonstrated some biological activities. In this study, the potential neuroprotective effects of these iridoids were evaluated through in silico and in vivo assays, using Caenorhabditis elegans (C. elegans) strains CF1553 (sod-3::GFP), GA800 (cat::GFP), and CL2166 (gst-4::GFP). The results suggested that neither compound appears to have good passive permeability through the blood–brain barrier (BBB). However, an active transport mechanism involving the glucose transporter GLUT-1 may be present, as both compounds contain glucose in their molecular structure. In addition, they can inhibit the activity of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). GP at 1 and 2 mM reversed the H₂O₂-induced increase in sod-3 expression, while ASP at 1 and 2 mM reversed the increase in gst-4 expression. Worm survival was more adversely affected by higher concentrations of GP than ASP, although both similarly reduced acetylcholinesterase activity. These findings suggest that GP and ASP exhibit very low toxicity both in silico and in vivo in C. elegans, and positively modulate key enzymes involved in antioxidant pathways, highlighting their potential for neuroprotective applications. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders. Full article

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article

The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) and barley (Hordeum vulgare) are key dietary staples with distinct genetic architectures influencing the biosynthesis and accumulation of these bioactive compounds. In this study, we explore the interaction and divergence of gene loci associated with GABA, RS, and alkaloid pathways in rice and barley, leveraging comparative genomics to identify conserved and species-specific regulatory mechanisms. We highlight key quantitative trait loci (QTLs) and candidate genes, such as GAD (glutamate decarboxylase) for GABA synthesis, SSIIa and GBSS for RS formation, and alkaloid biosynthesis genes including CYP80G2. Additionally, we discuss the health implications of these functional components, including their roles in reducing hypertension, managing diabetes, and exhibiting neuroprotective effects. Understanding the genetic differences between rice and barley in accumulating these compounds can guide biofortification strategies to enhance nutritional quality in cereal crops, ultimately benefiting human health and dietary outcomes. Full article

β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. Full article

Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal that SW exhibits rapid absorption but demonstrates low oral bioavailability due to the first-pass effect. Pharmacological studies have demonstrated that SW possesses a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective activities. Our analysis demonstrates that SW exerts remarkable therapeutic potential across multiple pathological conditions through coordinated modulation of key signaling cascades, including Nrf2/HO-1, NF-κB, MAPK, PI3K/Akt, and PPAR pathways. This comprehensive review systematically consolidates current knowledge on SW’s pharmacokinetic characteristics, toxicity, diverse biological activities, and underlying molecular mechanisms based on extensive preclinical evidence, establishing a scientific foundation for future drug development strategies and potential clinical applications of the potential natural lead compound. Full article

Cerebral ischemic-reperfusion injury (CIRI) involves mitochondrial dysfunction, with mitophagy playing a key role. Astragaloside IV (AS-IV) shows neuroprotective potential; however, its mechanisms related to mitochondrial function and apoptosis remain unclear. Methods: Using a rat MCAO/R model, we evaluated the AS-IV’s effects via neurological scores, TTC staining, and histopathology. Molecular assays and docking were used to analyze mitophagy (PINK1, Parkin, p62, ROS, Bcl-2, and BAX) and apoptosis markers. Results: AS-IV improved neurological function, reduced infarct volume, and alleviated neuronal/mitochondrial damage. It upregulated PINK1/Parkin, decreased p62, and modulated Bcl-2/Bax. Docking confirmed AS-IV binds PINK1/Parkin with high affinity. Conclusions: AS-IV protects against CIRI by regulating the PINK1/Parkin pathway, improving mitochondrial function, and inhibiting neuronal apoptosis, providing an experimental basis for the clinical use Full article

Although exercise is known to exert anti-inflammatory effects in neurodegenerative diseases, its specific impact and underlying mechanisms in Parkinson’s disease (PD) remain poorly understood. This study explores the effects of exercise on microglia-mediated neuroinflammation and apoptosis in a PD model, focusing on the role of irisin signaling in mediating these effects. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that a 10-week treadmill exercise regimen significantly enhanced motor function, reduced dopaminergic neuron loss, attenuated neuronal apoptosis, and alleviated neuroinflammation. Exercise also shifted microglia from a pro-inflammatory to an anti-inflammatory phenotype. Notably, levels of irisin, phosphorylated AMP-activated protein kinase (p-AMPK), and sirtuin 1 (Sirt1), which were decreased in the PD brain, were significantly increased following exercise. These beneficial effects were abolished by blocking the irisin receptor with cyclic arginine–glycine–aspartic acid–tyrosine–lysine (cycloRGDyk). Our results indicate that exercise promotes neuroprotection in PD by modulating microglial activation and the AMPK/Sirt1 pathway through irisin signaling, offering new insights into exercise-based therapeutic approaches for PD. Full article

Objective: To investigate the neuroprotective effects of a Rho-associated kinase (ROCK) inhibitor on retinal ganglion cells (RGCs) in vitro and in vivo. Methods: For in vivo studies, a unilateral optic nerve crush mouse model was established. Then, 100 mM Y-27632 (a ROCK inhibitor) or saline was applied to the experimental eyes once a day for 14 days. The effects of the ROCK inhibitor were evaluated by counting the surviving RGCs in the enucleated flat retina tissues and measuring the inner retinal thickness using optical coherence tomography (OCT), the amplitude of the electroretinogram (ERG), and the change in intraocular pressure (IOP). For the in vitro study, RGCs were isolated from five-day-old mice using a modified immunopanning method with magnetic beads. The isolated RGCs were incubated for 72 h with various concentrations of Y-27632, after which TUNEL assays were performed to determine the number of surviving RGCs. Results: Y-27632 has neuroprotective effects, as it significantly increased the number of surviving RGCs by approximately 6.3%. OCT and ERG data also revealed that Y-27632 induced neuroprotective effects in vivo; furthermore, Y-27632 reduced IOP by approximately 18.3%. The in vitro study revealed the dose-dependent neuroprotective effects of Y-27632, with the highest dose of Y-27632 (1000 nM) increasing the RGC survival rate after 72 h of incubation compared with that of the control. Conclusions: The ROCK inhibitor Y-27632 may exert some neuroprotective effects on RGCs when it is used as an eye drop through an IOP-independent mechanism. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article

Radiation therapy serves as a fundamental treatment for primary and metastatic brain tumors, whether used alone or combined with surgery and chemotherapy. Despite its oncological efficacy, this treatment paradigm frequently induces radiation-induced brain injury (RBI), a progressive neuropathological condition characterized by structural and functional damage to healthy cerebral parenchyma. Patients with RBI frequently develop affective disorders, particularly major depressive disorder and generalized anxiety disorder, which profoundly impair psychosocial functioning and quality of life. The pathophysiology involves complex mechanisms such as neuroinflammation, oxidative stress, blood–brain barrier disruption, and white matter damage. Current management strategies include antidepressants, corticosteroids, and neuroprotective agents, while emerging therapies targeting neuroinflammation and neural repair show promise. This review comprehensively examines the pathogenesis of RBI-related affective disorders and evaluates both conventional and novel treatment approaches. By synthesizing current evidence, we aim to provide insights for developing more effective interventions to improve patient outcomes and quality of life. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

Cognitive function is critical for overall health, with vitamin D’s impact under extensive investigation. This review explores the association between vitamin D and cognitive health, its neuroprotective mechanisms, and the therapeutic potential of supplementation in cognitive decline. Observational studies link low vitamin D levels to increased cognitive deterioration risk, particularly in Alzheimer’s disease, vascular dementia, Parkinson’s disease, and schizophrenia. Clinical trial results on vitamin D supplementation’s cognitive benefits are inconclusive. Vitamin D’s neuroprotective effects are complex, influencing cognitive abilities by interacting with neuronal and glial cells, modulating immune responses, and regulating key molecular pathways. Challenges remain in clinical applications, including determining optimal vitamin D levels, effective supplementation forms and doses, and identifying responsive populations. The review advocates for robust clinical trials to address these gaps, facilitating informed use of vitamin D in cognitive health. Future research should focus on the optimal timing, duration, and target groups for supplementation to enhance cognitive outcomes and reduce risks. Full article