Central nervous system agents in medicinal chemistry最新文献

{"title":"Protective Effect of Carvacrol against Oxidative Damage in Aged Rats.","authors":"Mohammad Amin Forqani, Mahsan Akbarian, Sabiheh Amirahmadi, Mohammad Bagher Khorrami, Mahmoud Hosseini, Fatemeh Forouzanfar","doi":"10.2174/0118715249303906240729074821","DOIUrl":"https://doi.org/10.2174/0118715249303906240729074821","url":null,"abstract":"<p><strong>Background: </strong>Aging affects cellular functions and impairs tissue homeostasis. Carvacrol, a polyphenolic compound, has been shown to exert a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer characteristics.</p><p><strong>Methods: </strong>This investigation aimed to evaluate the effect of carvacrol in elderly male rats. Carvacrol at a dose of 15 or 30 mg/kg was administrated daily per os for 60 days to aged rats. The liver, heart, and kidney samples were taken for the analysis of oxidative stress markers. Serum samples were used to evaluate liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST)).</p><p><strong>Results: </strong>The levels of malondialdehyde (MDA) in the liver, heart, and kidney tissues of aged rats were higher. Conversely, the level of thiol was lower in the mentioned tissues than in the young control group. The levels of MDA in the liver, heart, and kidney tissues of aged rats were significantly reduced by carvacrol, which was accompanied by increased levels of total thiol. ALT and AST levels were higher in the serum of aged rats than in the young control ones. Carvacrol decreased ALT and AST levels in the serum of aged rats versus aged control rats.</p><p><strong>Conclusion: </strong>Carvacrol can be effective in protecting susceptible aged tissues and organs by increasing antioxidant defenses and decreasing liver enzymes.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984114","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":"A Systematic Review of the Anti-seizure and Antiepileptic Effects and Mechanisms of Piperine.","authors":"Nasim Rahimi-Dehkordi, Saeid Heidari-Soureshjani, Sahar Rostamian","doi":"10.2174/0118715249297934240630111059","DOIUrl":"https://doi.org/10.2174/0118715249297934240630111059","url":null,"abstract":"<p><strong>Introduction and aim: </strong>Seizures due to epilepsy in any form cause a wide range of problems in a patient's physical, psychological, and social health. This study aimed to investigate piperine's anti-seizure and antiepileptic effects and mechanisms.</p><p><strong>Methods: </strong>In this systematic review study, which was conducted according to the principles of PRISMA 2020, the initial search was conducted on November 2, 2023, using EndNote software. Various databases such as PubMed, Cochrane Library, Web of Science, Embase, and Scopus were searched using specific keywords. After screening the articles, a form was designed according to the objectives of the study, and the information related to the included articles was entered in the form, and the studies were reviewed.</p><p><strong>Results: </strong>Piperine showed its antiepileptic activity by affecting the brain's antioxidant, anti-inflammatory, and anti-apoptotic activity. It also, by modulating brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA)ergic activity, can control seizures. In addition, piperine can help treat seizures and epilepsy by elevating 5-HT levels in the brain, modulating astrocyte and microglia function, modulatory effects on Ca2+ and NA+ channels, increasing antiepileptic drugs bioavailability and influencing protein and gene expression.</p><p><strong>Conclusion: </strong>In vivo and in vitro studies showed beneficial effects on treating epilepsy. Although clinical studies also showed similar results, these needed to be increased, and more clinical studies needed to be designed in this field.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857393","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":"Targeting Adenylate Cyclase: A Novel Concept for Stimulation of Neurogenesis and Pharmacotherapy of Alzheimer's Disease.","authors":"Gleb Nikolaevich Zyuz'kov, Larisa Arkad Evna Miroshnichenko, Tatyana Yur Evna Polykova, Elena Vladislavovna Simanina, Alexander Vasil Evich Chayikovskyi","doi":"10.2174/0118715249302264240715060630","DOIUrl":"https://doi.org/10.2174/0118715249302264240715060630","url":null,"abstract":"<p><strong>Background: </strong>The low effectiveness of existing pharmacotherapy strategies for Alzheimer's disease (AD) makes it necessary to develop a new concept for the treatment of this type of dementia. This search is promising to be carried out within the framework of the paradigm of targeting intracellular signaling pathways in Regenerative-Competent Cells (RCCs).</p><p><strong>Objective: </strong>The purpose of the research is to study the impact of adenylate cyclase (AC) inhibitor on disorders of the psychoemotional status in aged male C57BL/6 mice, as well as on the dynamics of the content and functioning of RCCs nervous tissue.</p><p><strong>Methods: </strong>We examined the effect of the AC inhibitor (2',5'-Dideoxyadenosine) on conditioned reflex activity, behavioral and emotional profile in a mouse AD model (16-month-old (aged) male C57BL/6 mice), as well as the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells in the subventricular zone of the cerebral hemispheres (SVZ).</p><p><strong>Results: </strong>In aged C57BL/6 mice, we found impairments in exploratory behavior, emotional reactivity, and memory, which are the characteristics of senile dementia. Therapy based on AC inhibition led to an increase in the number of NSCs and NPCs in the SVZ due to an increase in their proliferative activity. These changes were more pronounced in NCPs. At the same time, a decrease in the specialization intensity was recorded in NSCs. These phenomena developed against the background of increased secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. The neuroregenerative effects of 2',5'-dideoxyadenosine correlated with the correction of age-related disorders of the psychoemotional status in aged mice.</p><p><strong>Conclusion: </strong>The results provide the basis for the development of targeted drugs based on AC inhibitors to stimulate neurogenesis as an approach for the effective treatment of AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794261","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":"https://doi.org/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":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","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}

{"title":"Cutting-edge Approach of Carbon Nanostructures: Targeted Drug Delivery to Central Nervous System.","authors":"Venishaa S, Mridul Guleria, Prashant Kumar, Mithun Bhowmick, Pratibha Bhowmick, Sumel Ashique, Iqbal Husain, Radheshyam Pal","doi":"10.2174/0118715249305383240705045921","DOIUrl":"https://doi.org/10.2174/0118715249305383240705045921","url":null,"abstract":"<p><p>Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the bloodbrain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617813","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":"Comprehensive Review on Alzheimer's Disease: Natural Therapeutics, Gaps and Challenges.","authors":"Prem Shankar Mishra, Rakhi Mishra, Anuj Kumar","doi":"10.2174/0118715249307525240614073143","DOIUrl":"https://doi.org/10.2174/0118715249307525240614073143","url":null,"abstract":"<p><p>More than 20 million people worldwide have Alzheimer's disease (AD), making it the most prevalent disease. Patients with AD may live for at least a decade after diagnosis, making it the most common cause of disability in the elderly. Each year, 1% to 4% of the population is affected by AD, with prevalence peaking between ages 65 and 70 and declining to 6% among those over 85. Researchers have accumulated evidence on medicinal herbs that may reverse the pathogenesis of Alzheimer's disease. Alzheimer's disease (AD) is associated with severe memory loss, which can negatively impact social and professional life. The first neurotransmitter linked to Alzheimer's was acetylcholine (ACh). There is no known cure, and the available treatments are ineffective. Multiple studies indicate that Ayurvedic restorative herbs and their constituents may be effective in treating Alzheimer's disease. This technique emphasizes the fact that delaying or preventing Alzheimer's disease with the help of natural bio-actives could reduce the number of cases over the next half-century. To provide detailed information, the pathology and pathophysiology of Alzheimer's Disease are discussed in the text of this review, along with an overview of the neurotransmitters involved in the progression of the disease. The importance of different natural bioactives for the treatment of Alzheimer's disease is also outlined in the paper. The information contained in this paper can serve as a template for future research expressing the more beneficial role of other bioactive in acting as an adjuvant in the prevention and treatment of this disease, facing certain challenges and gaps with conventional drugs used to treat Alzheimer's disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473593","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":"The Smart Drug Delivery of Rotigotine Using Transdermal Patch for the Successful Management of Parkinson's Disease.","authors":"Jose Prakash Dharmian, Angelin Claret Seraphim PushpaNathan, Prakash Ramakrishnan, Raja Navamani Subramanian, Jayachandran David Levy, Pavazhaviji Palani, Venkateshwaran Krishnaswami","doi":"10.2174/0118715249289689240607064642","DOIUrl":"https://doi.org/10.2174/0118715249289689240607064642","url":null,"abstract":"<p><strong>Background: </strong>A Non-Ergot Dopamine Agonist (NEDA) rotigotine has been designed as a new transdermal drug delivery system.</p><p><strong>Aim: </strong>To maintain optimum homogeneity in drug content, the rotigotine transdermal patch was developed utilizing a solvent casting technique.</p><p><strong>Methods: </strong>The characteristics of a transdermal patch, including patch weight, folding endurance, patch thickness, surface morphology, tensile strength, swelling rate, surface pH, in vitro release studies, water retention rate, uniformity of drug content, and ex-vivo permeation studies, were determined.</p><p><strong>Results: </strong>In vitro drug release studies unequivocally demonstrated that drug release controlled polymer interactions. There was no apparent lag period before the drug release rate started to decline. The developed patch showed 70 ± 1.18 % of prolongation of drug release within 24 hours. The result of the penetration studies demonstrated that 61 ± 2.52% of rotigotine permeated through the epidermal barrier within 24 h.</p><p><strong>Conclusion: </strong>The developed transdermal patch comprising rotigotine was evidently placed on the dermis layer, and an appropriate dose was delivered into circulation for a longer time based on the aforementioned factors. The findings of this study illustrate the effective approach of transdermal patches to treat Parkinson's disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443944","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":"Harvesting Health: Phytochemicals in Cognitive Impairment Therapy.","authors":"Sanidhya Jain, Avijit Mazumder, Saumya Das, Pankaj Kumar Tyagi, Mvnl Chaitanya","doi":"10.2174/0118715249315826240603075900","DOIUrl":"https://doi.org/10.2174/0118715249315826240603075900","url":null,"abstract":"<p><p>Mild Cognitive Impairment (MCI) is swiftly emerging as a prevalent clinical concern within the elderly demographic. Willoughby spearheaded the pioneering investigation into the evolution of memory decline spanning from the age of 20 to 70. Employing a computerized substitution examination, he pinpointed a zenith in memory prowess at the age of 22, signifying the shift from infancy, succeeded by a gradual decline in later years in 1929. Cognitive impairment impacts various facets, encompassing cognition, memory, perceptual acuity, and linguistic proficiency. Compelling evidence indicates that genetic, dietary, and metabolic factors influence the trajectory of cognitive decline in this patient cohort. In addition to the widely recognized influence of the Mediterranean diet on cognitive function, numerous studies have delved into the potential impact of diverse phytochemicals on cognitive deterioration. Many of these compounds are renowned for their inflammation reducer or free-radical scavenger properties, coupled with their commendable acceptability and defense profiles. Phytochemicals sourced from medicinal plants play an essential role in upholding the intricate chemical equilibrium of the brain by modulating receptors linked to crucial inhibitory neurotransmitters. Across the annals of historical medicinal traditions, a multitude of plants have been cataloged for their efficacy in mitigating cognitive disorders. This study presents a concise examination of distinct medicinal herbs, highlighting their neuroprotective phytochemical components such as fatty acids, phenols, alkaloids, flavonoids, saponins, terpenes, and beyond. The principal objective of this inquiry is to meticulously inspect and provide discernment into the extant evidence concerning phytochemicals exhibiting clinically demonstrable effects on cognitive decline.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328144","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 In vivo and In vitro 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":"https://doi.org/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>Objective: </strong>This review scrutinizes both in-vivo and in-vitro screening models employed in Alzheimer's disease research. In-vivo 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, in-vivo models, in-vitro models, and screening mechanisms. Inclusion criteria were established to identify studies focused on in-vivo and in-vitro 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 in-vivo and in-vitro 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":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","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":"Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.","authors":"Abhitinder Kumar, Mohit Agrawal, Yogesh Murti, Simran Behl, Shivendra Kumar, Hema Chaudhary, Kuldeep Singh, Sunam Saha, Sameer Rastogi","doi":"10.2174/0118715249284798240509052913","DOIUrl":"https://doi.org/10.2174/0118715249284798240509052913","url":null,"abstract":"<p><strong>Objective: </strong>The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus.</p><p><strong>Materials and methods: </strong>Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue.</p><p><strong>Results: </strong>The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions.</p><p><strong>Conclusion: </strong>These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082873","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}