CNS & neurological disorders drug targets最新文献

{"title":"Cholinesterase Inhibitors in Alzheimer's Disease: Medicinal Chemistry, Mechanistic Insights, and Emerging Multitarget Strategies.","authors":"Anuradha Mehra, Rahul Sharma, Amit Mittal","doi":"10.2174/0118715273435274260907101735","DOIUrl":"https://doi.org/10.2174/0118715273435274260907101735","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading neurodegenerative disorder in the world. Although several decades of research have focused on its multifactorial pathogenesis, treating it remains a great challenge. The approved treatment options include cholinesterase inhibitors (ChEIs), which are the most common symptomatic treatment choice. These drugs act by inhibiting acetylcholinesterase (AChE) and, in some cases, butyrylcholinesterase (BuChE), preventing the breakdown of acetylcholine and increasing cholinergic neurotransmission in the brain. This review provides a broad consideration of ChEIs, focusing on their bioactivity, biochemical action, clinical significance, and SAR trends. It provides a comparative analysis of all the major chemical classes of ChEIs, namely the carbamates and organophosphates, as well as multiple heterocyclic scaffolds, with particular assessment of BBB permeability, metabolic stability, and toxicity attributes. Recent advances in medicinal chemistry have led to a shift in interest toward multi-target-directed ligands (MTDLs) that are designed not only to inhibit ChEs but also to exert antioxidant, anti-inflammatory, anti-amyloid, and metalchelating activity. These can target multiple pathogenic mechanisms to achieve a better therapeutic effect and neuroprotection. This review is based on a robust literature search conducted between 2020 and 2025. The progress, limitations, and prospects of ChEIs in the treatment of AD are critically assessed in this work. It also underscores the need for rational drug design to develop multitargetdirected drugs that may have disease-modifying effects, to overcome the limitations of existing symptomatic cholinesterase-inhibitor monotherapy.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019090","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":"Nanoparticle-mediated Therapeutic Inventions against Glioblastoma: A Narrative Review on Current Perspectives.","authors":"Bida Joshua John, Dauda Maibasha, Ratnakar Shukla, Adil Husain, Afza Ahmad, Shambhavi Kumari, Vidhi Arora, Gungun Sherawat, Rohit Kumar Tiwari","doi":"10.2174/0118715273453180260908055829","DOIUrl":"https://doi.org/10.2174/0118715273453180260908055829","url":null,"abstract":"<p><p>Glioblastoma (GB) is a highly aggressive tumor that demonstrates significant treatment resistance due to the blood-brain barrier (BBB) and resistance mechanisms of the tumor. Nanoparticle- based drug delivery systems (NDDS) can enhance drug bioavailability, enable targeted delivery, and provide controlled release. These nanoparticles can be engineered to target GB-specific biomarkers, such as EGFRvIII, which is expressed on glioma stem cells, to enhance treatment precision. A comprehensive literature review was conducted using the keywords \"Glioblastoma,\" \"Nanoparticles,\" \"Pathogenesis,\" and \"Treatment Resistance\" across PubMed, MEDLINE, Web of Science, ClinicalTrial. gov, Science Direct, and Google Scholar databases. Engineered nanoparticles have considerable potential to overcome major therapeutic obstacles in GB. Techniques such as surface functionalization (e.g., with cRGD or transferrin) and biomimetic coatings enable nanoparticles to cross the BBB, significantly increasing drug accumulation within brain tumors by up to 12-fold. This leads to improved anti-tumor efficacy, demonstrating significant reductions in tumor burden and improved survival in animal models. Additionally, these platforms are used to deliver genetic therapies, such as siRNA and miRNA, to specific cancer-driving genes. The ability to deliver drugs intranasally further enhances the therapeutic potential. Nanoparticle-based therapies have emerged as a promising approach in the treatment of GB and have successfully overcome barriers such as the BBB and treatment resistance. These methods have demonstrated robust preclinical outcomes, which emphasize their potential for clinical translation. Ongoing research is important to maximize the potential of these technologies and improve survival rates for patients with GB.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019045","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":"Exploring the Potential of Quinoline-Containing Pyrazoline Derivatives as Antidepressant Agents: <i>In Vivo</i> and <i>In Silico</i> Studies.","authors":"Bharti Sharma, Chahat, Pawan Kumar, Ajit Kumar, Pooja A Chawla","doi":"10.2174/0118715273408493260904055147","DOIUrl":"https://doi.org/10.2174/0118715273408493260904055147","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Depression is a common mental disorder, affecting over 300 million people worldwide. Currently available treatments, such as SSRIs, SNRIs, TCAs, and MAOIs, have limited effectiveness and cause side effects. The pharmacological potential of compounds based on diverse novel heterocyclic scaffolds, including quinoline-appended pyrazoline analogues, has been well recognized.</p><p><strong>Methods: </strong>Ten derivatives of 1, 3, 5-trisubstituted pyrazoline, namely BS-1 to BS-10, were synthesized from chalcone derivatives in reaction with thiosemicarbazide/semicarbazide analogues. The complexes were identified by physicochemical and spectral analyses (FT-IR, 1H-NMR, 13C-NMR), and in silico studies comprised molecular docking against MAO-A and molecular dynamics simulations. Drug-likeness and toxicity analysis was performed using SwissADME, PreADME, and Pro- ToxWeb. Antidepressant potentials were evaluated in vivo using the Forced Swim Test (FST) and Tail Suspension Test (TST) in Swiss albino mice; behavioral parameters and DPPH and H2O2 assays determined antioxidant activity.</p><p><strong>Results: </strong>Docking studies revealed strong binding to MAO-A, with the highest scores observed for BS-7 and BS-8 (-10.8 and -11.7 kcal/mol). Stable interactions were also identified in molecular dynamics simulations, particularly for BS-7. In vitro assays (DPPH) indicated antioxidant activity, and the IC50 values of BS-7, BS-8, and BS-10 were 43.65, 66.42, and 44.11 μg/mL, respectively. Also, BS-7 BS-8, and BS-4 compounds demonstrated antioxidant activity (H2O2) with IC50 values of 9.06 ± 2.12, 11.38 ±1.00, and 12.89 ±2.25 μM, respectively. In vivo screening showed that specific compounds, such as BS-8 (30 mg/kg), significantly reduced FST and TST immobility time (p < 0.0001), whereas BS-7 produced significant effects only in TST.</p><p><strong>Discussion: </strong>BS-8 demonstrated superior antidepressant-like activity compared to BS-7 in both FST and TST without affecting locomotor performance. In antioxidant assays, BS-7 showed moderate free-radical scavenging in the DPPH assay, whereas BS-8> BS-7 exhibited greater hydrogen peroxide (H2O2) scavenging activity, indicating complementary antioxidant profiles that may differentially contribute to their observed biological effects.</p><p><strong>Conclusion: </strong>Quinoline-based pyrazoline analogues BS-8 > BS-7 showed antidepressant-like and antioxidant activities without affecting locomotor or muscle function, indicating their potential as lead compounds for novel antidepressant development.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972635","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":"Effect of N-Acetylcysteine in Reducing Postoperative Cognitive Dysfunction after Anaesthesia in Elderly Patients Undergoing Day Surgery: A Randomized Controlled Study.","authors":"Jaishree Mohanbabu, Abishek Manogaran, Sri Harish Kumar Srinivasan, Anandan Prabakar Rohith, Kuppusamy Anand, Muhasaparur Ganesan Rajanandh","doi":"10.2174/0118715273485933260821105708","DOIUrl":"https://doi.org/10.2174/0118715273485933260821105708","url":null,"abstract":"<p><strong>Introduction: </strong>Postoperative cognitive dysfunction (POCD) refers to a decline in cognitive ability following surgery. N-acetylcysteine (NAC) has antioxidant and neuroprotective properties; however, clinical evidence supporting its role in reducing POCD in elderly patients undergoing day surgery remains limited. This study evaluated the effect of oral NAC on POCD recovery among older adults undergoing day surgery.</p><p><strong>Methods: </strong>This randomized controlled trial included elderly patients undergoing outpatient surgery with American Society of Anaesthesiologists physical status I-III. Participants received oral NAC (400-600 mg) or placebo. NAC was administered preoperatively and twice daily for two postoperative days. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at baseline (2 hours before surgery) and 24 hours postoperatively. Physiological recovery and readiness for discharge were assessed using the Modified Aldrete Score (MAS), while quality of recovery was evaluated using the Quality of Recovery-40 (QoR-40) questionnaire.</p><p><strong>Results: </strong>Of 417 randomized patients, 296 were included in the final analysis (148 in each group). Within-group analysis showed no significant change in MoCA scores from baseline to 24 hours postoperatively in either the test group (p = 0.959) or the control group (p = 0.734). No significant between- group difference was observed in MAS (p > 0.05). In contrast, QoR-40 was significantly higher in the Test group compared with the control group (p < 0.05). No drug-related adverse events were observed during the study period.</p><p><strong>Discussion: </strong>NAC improved quality of recovery but not postoperative cognitive function MoCA. Discharge readiness, MAS is unaffected. Hence, larger and longer follow-up investigations are needed.</p><p><strong>Conclusion: </strong>Oral NAC did not significantly affect early postoperative cognitive or physiological recovery in elderly day-surgery patients but was associated with improved quality of recovery.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972634","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 Gut-Brain Axis: Exploring the Role of Gut Microbiota in Alzheimer's Disease Pathogenesis and Therapeutics.","authors":"Javeria Fatima, Yasir Hasan Siddique","doi":"10.2174/0118715273460507260827112721","DOIUrl":"https://doi.org/10.2174/0118715273460507260827112721","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, and cognitive decline. Increasing evidence implicates the gut-brain axis as a key regulator of AD pathogenesis through immune, metabolic, and neuroendocrine pathways.</p><p><strong>Methods: </strong>This review systematically synthesizes recent preclinical and clinical studies investigating the role of gut microbiota in AD, focusing on microbial composition, mechanistic communication pathways, and microbiota-targeted therapeutic strategies.</p><p><strong>Results: </strong>Gut microbiota dysbiosis contributes to AD progression through multiple mechanisms, including activation of TLR4/NF-κB-mediated neuroinflammation, disruption of blood-brain barrier integrity, and altered microbial metabolite production, particularly short-chain fatty acids (SCFAs) and tryptophan-derived compounds. These changes influence amyloid deposition, tau phosphorylation, and synaptic dysfunction.</p><p><strong>Discussion: </strong>Gut microbiota dysbiosis plays a significant role in AD progression by promoting neuroinflammation, BBB dysfunction, and altered microbial metabolite production. Microbiota-targeted interventions, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have the potential to modulate these pathways and improve cognitive outcomes, although results vary across studies.</p><p><strong>Conclusions: </strong>The gut microbiota acts as an upstream regulator of AD pathology through interconnected molecular mechanisms. However, variability in study design, limited clinical validation, and lack of standardized protocols remain major challenges. Future research should focus on mechanistic validation using multi-omics approaches and the development of personalized microbiome-based therapeutic strategies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946329","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":"Circadian Rhythm Disruption in Alzheimer's Disease: Mechanistic Insights, Diagnostic Implications, and Emerging Chronotherapeutic Strategies: A Narrative Review.","authors":"Jasleen Kaur, Ritu Kainth, Roopal Mittal, Arshpreet Kaur, Ajay Singh Kushwah","doi":"10.2174/0118715273425623260210180623","DOIUrl":"https://doi.org/10.2174/0118715273425623260210180623","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex etiology that involves environmental, genetic, and metabolic components. Among these, circadian rhythm disruption has been seen critical but underexplored component in the pathogenesis of Alzheimer's disease. The suprachiasmatic nucleus (SCN), the central pacemaker of circadian regulation, coordinates all the physiological processes, such as sleep-wake cycles, metabolism, and neuroendocrine signalling. Tau-pathology, neuroinflammation, amyloid-β build-up, and cognitive decline in Alzheimer's disease are all becoming gradually linked to dysregulation of the system. A detailed review of literature was performed to study the role of circadian disruption in Alzheimer's disease. Alzheimer's disease-related circadian rhythm dysregulation is expressed through decreased melatonin secretion, sleep disturbances, and modified SCN signalling. Neuronal dysfunction could be caused by mutations in important clock genes (BMAL1, PER, CRY, and CLOCK). Sleep deprivation increases the buildup of amyloid-β and impairs glymphatic clearance. Also, tau pathology interrupts the circadian clock, further speeding up cognitive decline. Chronotherapies involving melatonin supplementation, light therapy, environment, and sleep hygiene provide promising effects in restoring circadian regulation and enhancing cognitive performance. According to the research from both experimental and clinical studies, there is a link between circadian rhythm abnormalities and Alzheimer's disease. Non-invasive biomarkers for the early identification of circadian nonalignment may aid in preventative measures. Researchers are currently looking into new treatment options that could slow down the progression of Alzheimer's disease. The integration of circadianbased therapies into individualised therapy paradigms for Alzheimer's disease patients should be the main focus of future research.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946341","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":"Cortisol Dysregulation as a Major Factor in the Development of Neurodegenerative Diseases, Drug Targets and Therapeutic Prospects: A Comprehensive Review.","authors":"Reza Hooshyari Ardakani, Mohadeseh Dashtaki, Seyed-Mahdi Mohamadi-Zarch, Seyyed Majid Bagheri","doi":"10.2174/0118715273466502260813092749","DOIUrl":"https://doi.org/10.2174/0118715273466502260813092749","url":null,"abstract":"<p><p>Cortisol, regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is critical for stress response, metabolism, and immune function. Its dysregulation is increasingly implicated in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). This review synthesizes evidence on cortisol's role in neurodegenerative disorders, exploring its mechanisms, clinical implications, and therapeutic potential. This study analyzed preclinical models, clinical studies, and biomarker data to elucidate cortisol's impact on neurodegeneration. Key mechanisms include glucocorticoid and mineralocorticoid receptor-mediated effects on synaptic plasticity, neuroinflammation, and oxidative stress. In AD, elevated cortisol accelerates cognitive decline, hippocampal atrophy, and amyloid-β accumulation. In PD, higher cortisol levels correlate with gait dysfunction and dopaminergic neuron loss. HD shows variable cortisol profiles, with early hypocortisolism shifting to hypercortisolism in later stages, linked to depression. In ALS, elevated cortisol hastens disease progression and neuroinflammation. In MS, HPA axis hyperactivity is associated with cognitive deficits and lesion activity, though it may support remyelination. Chronic stress exacerbates these effects across disorders, promoting neuronal vulnerability. Cortisol dysregulation is a significant contributor to neurodegenerative pathology, acting as both a biomarker and therapeutic target. Emerging interventions, including glucocorticoid receptor antagonists, cortisol synthesis inhibitors, and stress reduction strategies, show promise in mitigating neuronal damage. Personalized, stage-specific therapies and longitudinal studies are needed to optimize cortisol-targeted treatments for neurodegenerative diseases.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889704","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":"Nano-Magnetism for Precision Neuroscience: Biohybrid Magnetoelectric Nanocarriers as Next-Generation Neural Drug Delivery Platforms.","authors":"Shikha Baghel Chauhan, Aniket Bhardwaj, Chirag Jain, Indu Singh","doi":"10.2174/0118715273397455251030094458","DOIUrl":"https://doi.org/10.2174/0118715273397455251030094458","url":null,"abstract":"<p><p>Neuroscience is making tremendous progress toward precision medicine, with nanotechnology playing a critical role in overcoming hurdles to successful brain medication delivery. Nano magnetism, namely biohybrid magnetoelectric nanocarriers (MENs), has emerged as a potential method for targeted and non-invasive medication delivery in neurological illnesses. These nanocarriers possess magnetoelectric properties, enabling stimulus-responsive drug release that is externally controlled. This allows for precise targeting across the blood-brain barrier (BBB), with exceptional spatial and temporal resolution. MENs can deliver neurotherapeutics deep into brain regions by combining magnetic guidance with electrical stimulation, thereby improving treatment outcomes for conditions such as Alzheimer's, Parkinson's, epilepsy, and glioblastoma. Furthermore, their biohybrid nature, which is accomplished by functionalizing nanocarriers with biocompatible coatings, peptides, or membranes produced from neural cells, increases biostability, decreases immune response, and improves neuron targeting. This review investigates the underlying concepts of magnetoelectric nanocarriers, production processes, and interactions with brain tissue. It dives deeper into recent advances in precision neural drug delivery, including the effect of external magnetic and electric fields on regulated drug release, neurostimulation, and neuromodulation. While MENs have tremendous promise, long-term biocompatibility, precise control systems, and regulatory restrictions continue to impede clinical translation. Future research should concentrate on enhancing nanocarrier design, increasing targeting efficiency, and undertaking large-scale preclinical and clinical trials. Magnetoelectric nanocarriers have the potential to transform non-invasive neurotherapeutics by bridging the gap between nano magnetism and neuroscience, resulting in safer and more successful treatment paradigms for complex brain illnesses.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889694","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":"Combining Lycopene, Quercetin, and Poloxamer 188 Therapy Reduces Learning and Memory Deficits in the 3-nitropropionic Acid-induced Rat Model of Huntington's Disease.","authors":"Arti A Bhimanwar, Swati P Barangule, Hemlata M Nimje, Suchita P Dhamane, Virendra S Gomase","doi":"10.2174/0118715273450391260807100448","DOIUrl":"https://doi.org/10.2174/0118715273450391260807100448","url":null,"abstract":"<p><strong>Introduction: </strong>The current study was carried out to assess the pharmacological action of combine effect of Poloxamer 188, Lycopene, and Quercetin on memory and energy deficit in Huntington's disease-like signs induced by 3 Nitropropionic acid in Wistar rats.</p><p><strong>Methods: </strong>After one week of acclimatization all animals were randomly assigned in six groups, (n = 6), as normal control, Huntington's disease control, Lycopene treated (25 mg/kg po), Quercetin treated (50 mg/kg po), combinations with and without Poloxamer 188 (80 mg/kg po) with adjunct administration of 3 nitropropionic acid (10 mg/kg i.p.) except in normal control. Memory and energy deficits were induced by i.p. administration of 3 Nitropropionic acid (10 mg/kg) for 14 days. A novel object recognition test was assessed on the 14th and 15th days of the experiment, post-treatment, and other biochemical parameters were examined at the end of the experiment.</p><p><strong>Result: </strong>The results showed that the 3-nitropropionic acid administration for 14 days produced memory and energy deficits in rats. Moreover, the combination of Lycopene and Quercetin, with and without Poloxamer 188, showed significant effects on memory enhancement, energy deficit, and body weight compared to single-drug therapy. However, the combination did not produce a significant increase in brain weight compared to single-drug therapy. Moreover, the combination also showed remarkable enhancement in Succinate dehydrogenase activity and reduction in Lactate dehydrogenase activity compared to monotherapy.</p><p><strong>Discussion: </strong>The combined therapy of lycopene, quercetin, and poloxamer 188 significantly improved 3-nitropropionic acid-induced cognitive deficits by reducing oxidative stress and enhancing cholinergic function. This synergistic effect also normalized key mitochondrial enzymes, suggesting strong neuroprotective potential against Huntington's disease progression.</p><p><strong>Conclusion: </strong>Administration of 3-nitropropionic acid for 14 days produces memory and energy deficits in rats. Combining the effects of Lycopene and Quercetin, with or without Poloxamer 188, enhances memory and reduces energy deficit more effectively than mono-therapy. This study assessed the effects of combined lycopene, quercetin, and poloxamer 188 treatment on cognition and energy deficits in a 3-nitropropionic acid-induced rat model. Treating with a combination of the three compounds resulted in behavioral and biochemical improvements compared to the disease control group. There may be a tendency for the combined treatments to have additive effects on the subjects compared to individual treatments. However, the results of this study should be interpreted with caution.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889760","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":"Tanshinone IIA Improves Depression-like Behaviors in Ovariectomized Mice.","authors":"Wen Lin, Jiayan Li, Yi Deng, Li Mao, Jiajie Li, Fengbo Wang, Yuan Jiang","doi":"10.2174/0118715273492076260803052821","DOIUrl":"https://doi.org/10.2174/0118715273492076260803052821","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the effect of Tanshinone IIA (Tan IIA), a major component of the root of red-rooted Salvia miltiorrhiza Bunge, on depression-like behaviors in Ovariectomized (OVX) mice and to explore the potential mechanisms.</p><p><strong>Methods: </strong>A total of 30 female C57/BL6 mice were randomly assigned to three groups (n = 10 per group): Sham, OVX, and Tan IIA. Mice in the Sham group were subjected to a sham operation, whereas those in the OVX and Tan IIA groups were subjected to an ovariectomy to simulate menopause. OVX mice in the Tan IIA group were treated with Tan IIA (10 mg/kg) for 8 weeks. After the intervention, behavioral tests, including the Open Field Test (OFT), Forced Swimming Test (FST), and Tail Suspension Test (TST), were performed to assess the effect of Tan IIA on depression-like behaviors in OVX mice. Histopathology examination was conducted to assess the neuroprotective effect of Tan IIA on hippocampal neurons. Tissue total iron content analysis, Malondialdehyde (MDA) analysis, and Glutathione (GSH) analysis were measured to assess iron metabolism regulation and antioxidant effects, respectively. Hippocampal mitochondrial morphology was examined using a Transmission Electron Microscope (TEM) to assess the anti-ferroptotic capacity of Tan IIA. Western blot analysis was used to measure the expression of Nrf2, SLC7A11, and GPX4 to assess the effect of Tan IIA on the Nrf2 pathway. Molecular docking was conducted to verify the binding ability between Tan IIA and core protein targets of the Nrf2 pathway.</p><p><strong>Results: </strong>Tan IIA treatment effectively alleviated anxiety-like and depression-like behaviors in OVX mice, reduced iron accumulation and lipid oxidative stress, and inhibited ferroptosis in the hippocampal neurons. Moreover, Tan IIA exhibits high binding affinity for Nrf2, SLC7A11, and GPX4, which contribute to increasing expression levels of the Nrf2/SLC7A11/GPX4 pathway in the hippocampus of OVX mice.</p><p><strong>Discussion: </strong>Bilateral ovariectomy induced depressive and anxiety-like symptoms in female C57/BL6 mice. The presence of hippocampal ferroptosis was closely related to these symptoms. The effects of Tan IIA on hippocampal ferroptosis and the Nrf2 pathway likely contributed to the alleviation of depression- like behaviors in OVX mice.</p><p><strong>Conclusion: </strong>Tan IIA inhibits hippocampal ferroptosis and alleviates depression-like behaviors in OVX mice, which may be related to the up-regulation of the Nrf2/SLC7A11/GPX4 pathway.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809656","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}