Central nervous system agents in medicinal chemistry最新文献

{"title":"Analysis of Vit B6 in Raw Banana Peel, Phytochemical Screening, and Neuroprotective Effects.","authors":"Priyabrata Pradhan, Vineet Kumar Rai, Saroj Kumar Rout, Biswakanth Kar, Durgamadhab Kar, Shakti Ketan Prusty, Goutam Ghosh, Goutam Rath","doi":"10.2174/0118715249373404250403072724","DOIUrl":"https://doi.org/10.2174/0118715249373404250403072724","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy contributes significantly to the burden of mental illness, with an estimated 50 million cases globally. Neuroprotection with herbal bioactives is a promising therapeutic strategy for the prevention and treatment of temporal lobe epilepsy. Banana peel is rich in antioxidants and anti-inflammatory compounds. It has the potency to protect against neuronal apoptosis primarily due to the presence of Vit B6 and flavones.</p><p><strong>Objectives: </strong>This: study investigated the neuroprotective effects of Hydro-Alcoholic Extracts (HAE) of banana peel, prepared at solvent ratios of 90:10, 80:20, and 70:30, focusing on their anti- apoptotic, antioxidant, and anti-inflammatory activities.</p><p><strong>Methods: </strong>Neurons or neuronal cell lines were treated with HAE at 10-200 μg/mL concentrations. Apoptotic markers (cleaved caspase-3 and Bcl-2) were evaluated using ELISA, and the cleaved caspase-3/Bcl-2 ratio was calculated. Antioxidant effects were assessed via Glutamate Decarboxylase (GAD) and catalase activity assays, while pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were quantified. Cell viability was analyzed using the MTT assay, and IC50 values were determined for apoptosis inhibition.</p><p><strong>Results: </strong>HAE (90:10) at 100 μg/mL significantly reduced the cleaved caspase-3/Bcl-2 ratio (0.45±0.02), with an IC50 of 37.5±2.1 μg/mL, demonstrating superior anti-apoptotic activity. HAE (80:20) and HAE (70:30) exhibited IC50 values of 48.2±2.5 μg/mL and 62.7±3.0 μg/mL, respectively, indicating comparatively lower potency. Enhanced GAD (121.4±5.2 U/mg) and catalase (89.7±3.4 U/mg) activities with HAE (90:10) highlight its potent antioxidant effects. Significant reductions in pro-inflammatory markers, including TNF-α (decreased by 45.6±2.3% at 100 μg/mL), further underscore its anti-inflammatory potential. The MTT assay revealed improved cell viability, with HAE (90:10) maintaining 93.5±2.6% viability at 100 μg/mL. The superior performance of HAE (90:10) can be attributed to its optimized balance of bioactive compounds, supporting its neuroprotective properties.</p><p><strong>Conclusion: </strong>HAE (90:10) emerged as the most promising candidate for neuroprotection, demonstrating potent anti-apoptotic, antioxidant, and anti-inflammatory effects. These findings suggest its potential application in managing neurodegenerative disorders, warranting further in vivo and clinical studies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the Antidepressant Effects of the Combination of Agmatine and Melatonin Following Restraint Stress in Mice: the Role of Oxidative Factors.","authors":"Saeed Mehrzadi, Ali Jamshidi Naeini, Fahime Azimirad, Azam Hosseinzadeh","doi":"10.2174/0118715249347833250307041355","DOIUrl":"https://doi.org/10.2174/0118715249347833250307041355","url":null,"abstract":"<p><strong>Objective: </strong>Major Depressive Disorder (MDD) is a psychiatric disorder that has a tight connection to stressful experiences, decreased levels of endogenous antioxidants and enhanced levels of oxidative stress. We drafted this research to define the results of combining agmatine and melatonin on stress-induced depression in mice.</p><p><strong>Methods: </strong>Experimental groups included the non-stressed group treated with vehicle (ethanol at a concentration of 0.0005%), stressed vehicle (ethanol at a concentration of 0.0005%)-treated group, group treated with fluoxetine (10 mg/kg/day), group treated with melatonin (10 mg/kg/day), group treated with agmatine (1 mg/kg/day), group receiving a combination of melatonin (10 mg/kg/day) and agmatine (1 mg/kg/day). The animals were subjected to restraint stress for two hours daily for a duration of one week, concurrently with the daily oral administration of agents through drinking water. Open field test and forced swimming test were operated on the 8th day. The oxidative stress markers were measured in the mice hippocampus.</p><p><strong>Results: </strong>Stress led to the elevation of immobility time. The combination group showed a significant effect in comparison to the agmatine and melatonin groups. The combination of melatonin and agmatine was successful in the elevation of hippocampus catalase activity; and this effect was comparable in the fluoxetine group. We observed enhancement of superoxide dismutase activity in treatment groups and reduction in malondialdehyde levels in melatonin, agmatine and combination groups.</p><p><strong>Conclusion: </strong>A combination of agmatine and melatonin improves stress-induced depression more effectively than each alone, which may result from suppressing oxidative stress.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Pharmacophore Responsible for the JNK3 Enzyme Inhibition using KPLS-based QSAR Analysis.","authors":"Ravi Kumar Rajan, Maida Engels, Umaa Kuppuswamy","doi":"10.2174/0118715249345667250216034023","DOIUrl":"https://doi.org/10.2174/0118715249345667250216034023","url":null,"abstract":"<p><strong>Background: </strong>The pharmacophoric approach relies on the theory of possessing ubiquitous chemical functionalities, and carrying a uniform spatial conformation that provides a route to enhanced potency on the same target receptor. JNK3, also known as c-Jun N-terminal kinase 3, is a protein kinase that plays a crucial role in various cellular processes, particularly in the central nervous system (CNS). In this study, a kernel-based partial least square (KPLS)- based Two-dimensional Quantitative structural activity relationship (2D QSAR) model to predict pharmacophores responsible for c-Jun-N-terminal kinase 3 (JNK3) inhibition.</p><p><strong>Method: </strong>A library of small molecule JNK3 inhibitors was created from the literature, and a predictive model was built using Canvas 2.6.</p><p><strong>Result: </strong>The analysis revealed key structural determinants of activity. Compounds with high pIC50 values (>6) showed numerous favorable contributions, particularly secondary benzamide nitrogen and methylene groups. Steric effects were more influential than inductive effects, with bulkier groups like t-butyl reducing activity. Positive contributions were observed with OH, OCH3, and -F substituents, while unfavorable effects were linked to tertiary nitrogen, methyl, and primary amino groups. Substituted sulphonamides and benzotriazole moieties enhanced activity unless modified with amino or carbonyl groups. Favorable contributions were noted for terminal heterocyclic rings like pyrimidinyl acetonitrile, whereas phenyl substitutions and certain piperazine configurations were detrimental. Hydrogen in the urea moiety and avoiding bulky substitutions were crucial for activity. These insights guide the design of potent JNK3 inhibitors.</p><p><strong>Conclusion: </strong>The present study highlights the significant impact of substituents on molecular activity, with steric effects, particularly on the phenyl ring, playing a dominant role. Favorable contributions are linked to substitutions like hydroxyl, methoxy, and fluorine, while bulky and meta substitutions reduce activity. Functional groups like unsubstituted sulfonamide or free hydrogen in urea are crucial for activity. Insights into steric, electronic, and positional factors, combined with analysis of JNK3 inhibitors, will guide the design of more selective molecules.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of the Impact of Prenatal Depression on the Newborn Intestinal Microbiota.","authors":"Wafaa Taha, Oumaima Anachad, Amine Taouil, Chaimaa Saadoune, Mariame El Messal, Faiza Bennis, Fatima Chegdani","doi":"10.2174/0118715249361952250209084153","DOIUrl":"https://doi.org/10.2174/0118715249361952250209084153","url":null,"abstract":"<p><strong>Background: </strong>More than 15% of women develop symptoms of depression during pregnancy, which often affects the mental and physical development of the newborn by altering its intestinal microbiota. Previous studies revealed that the gut microbiota plays a crucial role in the maturation of systems involved in the gut-brain axis, including the gastrointestinal system, the immune system, and the hypothalamic-pituitary-adrenal system axis.</p><p><strong>Methods: </strong>This study aims to explore the cross-talk between the prenatal depression process and neonatal intestinal microbiota diversity. A total of 100 differentially expressed genes (DEGs) associated with prenatal depression were collected from various scientific publications and databases. Bioinformatics tools were used to analyze these DEGs. The STRING database. ToppGene database and DICE were employed for this integrative analysis.</p><p><strong>Results: </strong>The network generated by the STRING database identified six pivotal genes: TNF, BDNF, IL-6, NR3C1, IGF2, and POMC. These genes regulate response to endogenous hormones, particularly cortisol secretion in newborns, as well as inhibiting serotonin secretion. Moreover, these genes are linked to major depressive disorder and other mental diseases, contributing to maternal and neonatal gut microbiota dysbiosis. Analysis using ToppGene and DICE's further validated the biological processes identified by String, including the regulation of cellular cortisol secretion, metabolic processes, and serotonin inhibition.</p><p><strong>Conclusion: </strong>The bioinformatics tools employed in this study allowed us to identify pivotal genes involved in prenatal depression, their associated signaling pathways, and their roles in modulating maternal and neonatal gut microbiota.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation, Development and Evaluation of Effervescent Tablet of Green Tea (Camellia sinensis).","authors":"Prabhjot Kaur, Geeta Deswal, Bhawna Chopra, Priyanka Kriplani, Ajmer Singh Grewal, Ashwani K Dhingra","doi":"10.2174/0118715249333134250116112001","DOIUrl":"https://doi.org/10.2174/0118715249333134250116112001","url":null,"abstract":"<p><strong>Background: </strong>Camellia sinensis has an extensive variety of pharmacological properties, including neuroprotection, photo-aging resistance, stress resistance, antioxidant, anti-tumour, hypoglycemic, antibacterial, and antiviral effects tracing a good potential in addressing illness and preventing disease. Challenges with conventional dosage forms include patient incompatibility, improper dosing, the inclusion of microplastics, etc. Objective: The present work aims to deliver a novel formulation devoid of microplastics and with improved consumer compliance.</p><p><strong>Methods: </strong>Wet granulation was used to formulate 500 mg Camellia sinensis effervescent tablets, with improved effervescent time and rapid release. Citric acid and sodium bicarbonate's impacts on disintegration time and pH were examined using a factorial design. Pre-compression variables were assessed for the granule mixture. Post-compression criteria were employed to assess effervescent tablets. The optimum formulation was selected using a central composite response surface and assessment criteria.</p><p><strong>Results: </strong>The physicochemical characteristics of the developed formulations were significantly influenced by the independent factors. Low concentrations of sodium bicarbonate have positive impact on pH whereas high concentrations of sodium bicarbonate as well as citric acid enhance disintegration time. The design outcomes showed that the optimized effervescent tablets (F10) prepared with 697.5 mg and 448.38 mg of citric acid and sodium bicarbonate respectively had good physicochemical properties.</p><p><strong>Conclusion: </strong>In compliance with present quality standards, factorial design was efficiently utilized for the development of Camellia sinensis effervescent tablets. It was concluded that green tea effervescent tablet (F10) would function as a substitute for conventional green tea powder along with green tea bags as a means of administration.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Safety and Efficacy of Cuprum metallicum in Zebrafish and Mouse Models as a Potential Drug Candidate for the Management of Seizures.","authors":"Mahima Sharma, Vara Prasad Saka, Godlaveti Vijay Narasimha Kumar, Sangita Behera, Rajkumar Regar, Pankaj Gupta, Ritika H Narula","doi":"10.2174/0118715249345785250114222749","DOIUrl":"https://doi.org/10.2174/0118715249345785250114222749","url":null,"abstract":"<p><strong>Background: </strong>In an alternative medicinal system, Cuprum metallicum (CM) is used for the management of seizure-like conditions. However, there is a lack of scientific evidence regarding its effect.</p><p><strong>Objective: </strong>The present study aimed to evaluate the effect of CM against Pentylenetetrazoleinduced seizures in zebrafish and mice.</p><p><strong>Methods: </strong>Zebrafish were exposed to CM-6C, CM-30C, and valproic acid for 1 Hr then fish were exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C, CM-30C, and valproic acid for 10 days. After 30 min of the last dose, pentylenetetrazole was administered intraperitoneally. Observations during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ), tonic-clonic seizures, and the severity of seizure and survival protection after 24 Hrs.</p><p><strong>Results: </strong>PTZ exposure significantly decreased the latency from score-1 to score-5, which CM-6C and 30C significantly increased. Furthermore, CM-6C and 30C normalized the locomotor activity affected by PTZ exposure. Among the animals treated with the CM-6C and 30C, significantly increased latency to FMJ, tonic-clonic seizures, and survival protection compared to the PTZ group of Cuprum met.</p><p><strong>Conclusion: </strong>The results of the study indicate that CM 6C and 30C have the potential to work against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the treatment of epilepsy.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimethyl Fumarate Attenuates Behavioral and Structural Impairments Associated with Brain Ischemia in Rats.","authors":"Mohammad Bakhtiari, Masoumeh Emamghoreishi, Maryam Khastkhodaei Ardakani, Mohammad Reza Namavar","doi":"10.2174/0118715249345683250116080547","DOIUrl":"https://doi.org/10.2174/0118715249345683250116080547","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke remains one of the leading causes of death and physical and mental disability. Oxidative stress, free radicals, and inflammation play critical roles in ischemic brain damage. Free radical scavengers such as edaravone and dimethyl fumarate (DMF), known for their antioxidant and anti-inflammatory properties, are considered promising targets for ischemic stroke treatment. This study aimed to assess the impact of these drugs on brain ischemia.</p><p><strong>Methods: </strong>Forty-nine rats were randomly divided into seven groups: sham, edaravone, and DMF controls, as well as edaravone, DMF 5, 15, and 30 groups. Middle cerebral artery occlusion (MCAO) was induced in all groups except the sham group. The MCAO groups were administered with either the vehicle, edaravone (3 mg/kg), or DMF at doses of 5, 15, and 30 mg/kg twice daily for 14 days. Neurobehavioral assessments were conducted throughout the experiment, and anatomical changes in the brain were evaluated using stereological methods.</p><p><strong>Results: </strong>Edaravone and three doses of DMF improved neurobehavioral functions. All treated rats showed a reduction in the ischemic volume and cell loss in the brain regions when compared with the control animals. MCAO reduced the total number of neurons and just DMF doses had a significant effect on this factor. Interestingly, MCAO increased the number of non-neurons and only the DMF 30 group significantly decreased this parameter. DMF 30 was more effective in ischemic stroke.</p><p><strong>Conclusions: </strong>Although edaravone improved neurological functions and reduced the size of brain ischemia and cell loss, DMF, especially at higher doses, exerted a more beneficial effect on these parameters. Therefore, DMF could be proposed as a reinforcement to currently conventional therapies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Plausible Role of Potassium Channel Openers in Alzheimer's Disease.","authors":"Sarvesh Kumar, Bhupesh Sharma, Anjana Sharma, Nitin Sharma","doi":"10.2174/0118715249330827240819040302","DOIUrl":"10.2174/0118715249330827240819040302","url":null,"abstract":"","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"87-90"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on Alzheimer's Disease (AD) Involving the Use of <i>In vivo</i> and <i>In vitro</i> Models and Mechanisms.","authors":"Sweta Sinha, Pranay Wal, Prakash Goudanavar, Surisetti Divya, Vishwadeepak Kimothi, Divya Jyothi, Mukesh Chandra Sharma, Ankita Wal","doi":"10.2174/0118715249293642240522054929","DOIUrl":"10.2174/0118715249293642240522054929","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the progressive formation of extracellular amyloid plaques, intracellular neurofibrillary tangles, inflammation, and impaired antioxidant systems. Early detection and intervention are vital for managing AD effectively.</p><p><strong>Objectives: </strong>This review scrutinizes both <i>in-vivo</i> and <i>in-vitro</i> screening models employed in Alzheimer's disease research. <i>in-vivo</i> models, including transgenic mice expressing AD-related mutations, offer profound insights into disease progression and potential therapeutic targets. A thorough understanding of these models and mechanisms will facilitate the development of novel therapies and interventions for Alzheimer's disease. This review aims to provide an overview of the current experimental models in AD research, assess their strengths and weaknesses as model systems, and underscore the future prospects of experimental AD modeling.</p><p><strong>Methods: </strong>We conducted a systematic literature search across multiple databases, such as Pub- Med, Bentham Science, Elsevier, Springer Nature, Wiley, and Research Gate. The search strategy incorporated pertinent keywords related to Alzheimer's disease, <i>in-vivo</i> models, <i>in-vitro</i> models, and screening mechanisms. Inclusion criteria were established to identify studies focused on <i>in-vivo</i> and <i>in-vitro</i> screening models and their mechanisms in Alzheimer's disease research. Studies not meeting the predefined criteria were excluded from the review.</p><p><strong>Results: </strong>A well-structured experimental animal model can yield significant insights into the neurobiology of AD, enhancing our comprehension of its pathogenesis and the potential for cutting-edge therapeutic strategies. Given the limited efficacy of current AD medications, there is a pressing need for the development of experimental models that can mimic the disease, particularly in pre-symptomatic stages, to investigate prevention and treatment approaches. To address this requirement, numerous experimental models replicating human AD pathology have been established, serving as invaluable tools for assessing potential treatments.</p><p><strong>Conclusion: </strong>In summary, this comprehensive review underscores the pivotal role of <i>in-vivo</i> and <i>in-vitro</i> screening models in advancing our understanding of Alzheimer's disease. These models offer invaluable insights into disease progression, pathological mechanisms, and potential therapeutic targets. By conducting a rigorous investigation and evaluation of these models and mechanisms, effective screening and treatment methods for Alzheimer's disease can be devised. The review also outlines future research directions and areas for enhancing AD screening models.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"123-142"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-site APP-cleaving Enzyme-1 Inhibitory Role of Natural Flavonoids in the Treatment of Alzheimer's Disease.","authors":"Sandeep Singh, Virendra Kushwaha, Shriram Sisodia, Shivendra Kumar, Kantrol Kumar Sahu","doi":"10.2174/0118715249315049240710063455","DOIUrl":"10.2174/0118715249315049240710063455","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive function, including memory loss, reasoning difficulties, and disorientation. Its hallmark features include the formation of neurofibrillary tangles and neuritic plaques in the brain, disrupting normal neuronal function. Neurofibrillary tangles, composed of phosphorylated tau protein and neuritic plaques, containing amyloid-β protein (Aβ) aggregates, contribute to the degenerative process. The discovery of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in 1999 revolutionized our understanding of AD pathogenesis. BACE1 plays a crucial role in the production of Aβ, the toxic protein implicated in AD progression. Elevated levels of BACE1 have been observed in AD brains and bodily fluids, underscoring its significance in disease onset and progression. Despite setbacks in clinical trials of BACE1 inhibitors due to efficacy and safety concerns, targeting BACE1 remains a promising therapeutic strategy for early-stage AD. Natural flavonoids have emerged as potential BACE1 inhibitors, demonstrating the ability to reduce Aβ production in neuronal cells and inhibit BACE1 activity. In our review, we delve into the pathophysiology of AD, highlighting the central role of BACE1 in Aβ production and disease progression. We explore the therapeutic potential of BACE1 inhibitors, including natural flavonoids, in controlling AD symptoms. Additionally, we provide insights into ongoing clinical trials and available patents in this field, shedding light on future directions for AD treatment research.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"39-48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}