Metabolic brain disease最新文献

{"title":"Amomum tsao-ko crevost et lemaire ameliorates depression-like behaviors and hippocampal inflammation by inhibiting microglia activation and HMGB1/TLR4/NF-κB pathway in diabetic mice with depression.","authors":"Zhen Wang, Huilin Ren, Caixia Wang, Ruixue Min, Yue Ma, Yanli Ma, Xiaofeng Zhang","doi":"10.1007/s11011-025-01592-z","DOIUrl":"https://doi.org/10.1007/s11011-025-01592-z","url":null,"abstract":"<p><p>Diabetic depression may be closely related to hippocampal inflammation. We hypothesized that Amomum tsao-ko Crevost et Lemaire (A. tsao-ko) might ameliorate depression-like behavior and glucose intolerance by modulating hippocampal inflammation. UPLC-Q-Exactive-MS/MS was used to identified the constituents in the ethanol extract of A. tsao-ko (EEAT). Then a diabetic depression (DD) model was established and treated for 4 weeks. Depression-like behaviors were assessed using the open field test, sucrose preference test and tail suspension test. The neuronal injury was observed by hematoxylin-eosin staining and Nissl staining. Oral glucose tolerance test, fasting blood glucose, hemoglobin Alc, fasting insulin and homeostasis model assessment of insulin resistance were used to evaluate the effects of EEAT on glucose metabolism. Serum lipids, neurotransmitters, neuroendocrine and inflammation levels were detected by biochemical kits and enzyme-linked immunosorbent assay. Activation of microglia markers was detected by immunofluorescence. Western blotting was used to detect the effect of EEAT on the HMGB1/TLR4/NF-κB protein expression. 48 chemical components were identified from EEAT. Animal experiments showed that EEAT improved the levels of glucose and lipid metabolism, alleviated depression-like behaviors, decreased the level of neurotransmitters and increased the secretion of neuroendocrine-related hormones. The activation of microglia and immunofluorescence intensity of neurogenesis also improved. At the same time, the expression of HMGB1, TLR4 and NF-κB proteins in the inflammatory pathway was also inhibited. EEAT had effects on improving DD symptoms, which may be achieved by down-regulating the HMGB1/TLR4/NF-κB protein expression.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"164"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The beneficial effects of D-allose and D-allulose on the brain under ischemic stroke and obese-insulin resistant conditions: evidence from in vitro to clinical studies.","authors":"Yanmei Huang, Chanisa Thonusin, Masaaki Tokuda, Nipon Chattipakorn, Siriporn C Chattipakorn","doi":"10.1007/s11011-025-01580-3","DOIUrl":"https://doi.org/10.1007/s11011-025-01580-3","url":null,"abstract":"<p><p>Ischemic stroke, and obese-insulin resistance are common pathological conditions that lead to brain injury, resulting in neurodegeneration, brain atrophy, and cognitive dysfunction. Rare sugars, which are scarce monosaccharide in nature, have been investigated as a potential treatment for these adverse conditions. However, the beneficial effects of rare sugars on the brain have never been summarized. Therefore, this article comprehensively summarizes and discusses the benefits of rare sugars on the brain under physiological condition, ischemic stroke, and obese-insulin resistance. The potential mechanisms mediating these benefits of rare sugars are also described. Any contradictory findings are also included. This article adds weight to the impetus for further investigations into the applications of rare sugars as a novel therapeutic paradigm in clinical application.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"162"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop.","authors":"Lijuan Song, Yige Wu, Lijun Yin, Yanzhe Duan, Jianlin Hua, Mengwei Rong, Kexin Liu, Junjun Yin, Dong Ma, Ce Zhang, Baoguo Xiao, Cungen Ma","doi":"10.1007/s11011-025-01581-2","DOIUrl":"10.1007/s11011-025-01581-2","url":null,"abstract":"<p><p>Lipocalin-2 (LCN2), an acute phase protein mainly expressed in astrocytes (Ast), is closely related to the production of inflammatory cytokines following ischemic stroke. During the pathophysiological process of ischemic stroke, the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is activated. Despite evidence suggesting some link between the two, the relationship between the JAK2/STAT3 signaling pathway and the LCN2 expression in Ast following brain ischemia is incompletely understood. Hydroxysafflower yellow A (HSYA), an active ingredient found in Carthamus tinctorius L flowers, has been demonstrated to effectively mitigate cerebral ischemia via its anti-inflammatory effect. However, whether HSYA mitigates the neuroinflammatory damage after ischemic stroke by disrupting the interaction between the JAK2/STAT3 signaling pathway and LCN2 in Ast is unknown. Focusing on these two scientific questions, we established an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and in vitro primary astrocyte oxygen glucose deprivation/reperfusion (OGD/R) model. In vivo results showed that HSYA treatment alleviated nerve damage and inhibited the expression of LCN2 and inflammatory factors in Ast. In vitro results showed after OGD/R the expression of LCN2 and inflammatory cytokines increased and the JAK2/STAT3 was activated in Ast. Meanwhile, after OGD/R the JAK2/STAT3 activation in Ast increased LCN2 expression, and the inhibition of LCN2 expression by HSYA decreased the JAK2/STAT3 activation in Ast. These findings suggest that there is an interaction between the LCN2 and JAK2/STAT3 in Ast after ischemic stroke, which can enhance the inflammatory factors and exacerbate neuroinflammatory injury. Therefore, we conclude that HSYA may inhibit the LCN2/STAT3 loop in Ast, thereby mitigating neuroinflammation after cerebral ischemia.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"161"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin ameliorates ischemic/reperfusion injury by inhibiting ferroptosis.","authors":"Hua Li, Jin-Xia Li, Yi-di Zeng, Cai-Xing Zheng, Si-Si Dai, Jian Yi, Xu-Dong Song, Ting Liu, Wang-Hua Liu","doi":"10.1007/s11011-025-01588-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01588-9","url":null,"abstract":"<p><p>Ischaemic stroke is a large disease burden worldwide. Thrombolysis and thrombectomy are the main treatment methods for cerebral ischemia-reperfusion (I/R) injury. Luteolin, as a flavonoid compound, has an antagonistic effect on inflammation, oxidative stress, and tumorigenesis in disease. Therefore, the primary objective of this study is to determine the role of luteolin in cerebral I/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells and a cerebral I/R rat model were established. Cell viability and death were verified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide staining. The glutathione/oxidized glutathione (GSH/GSSG) ratio, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were determined using corresponding kits. Solute Carrier Family 7 Member 11 (SLC7A11), nuclear transcription factor erythroid 2-related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) levels were analyzed by western blotting. In addition, the infarct volume of brain tissues was examined by tetrazolium chloride (TTC) staining. Luteolin treatment significantly enhanced cell viability, decreased LDH release and intracellular ROS and MDA levels, and increased the GSH/GSSG ratio and SOD activity in OGD/R-treated BV2 cells. PI staining demonstrated that cell death was inhibited after luteolin treatment. Additionally, luteolin treatment significantly increased the SLC7A11, NRF2, and GPX4 protein levels. After treatment with ML385, an NRF2 inhibitor, the influence of luteolin on OGD/R-treated BV2 cells was reversed. Moreover, luteolin treatment significantly decreased the neurological score and infarct area in the brain tissues of cerebral I/R rats. Our research demonstrated that luteolin treatment inhibited ferroptosis by enhancing antioxidant functions through the NRF2 pathway, which provides a promising method for treating cerebral I/R injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"159"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate alleviated hippocampal neuron pyroptosis by down-regulating NLRP3 in rats with cerebral small vessel disease.","authors":"Xiaokun Wang, Hequan Zhong, Xiangyu Kong, Hongqiao Wei, Bing Li","doi":"10.1007/s11011-025-01590-1","DOIUrl":"10.1007/s11011-025-01590-1","url":null,"abstract":"<p><p>Our study aims to investigate the potential of artesunate (ART) in improving learning and memory function by down-regulating NLRP3 and consequently affecting pyroptosis levels in the brains of rats with cerebral small vessel disease (CSVD). Initially, Sprague-Dawley (SD) rats were randomly assigned to five groups: the solvent sham operation group, solvent model group, low-dose ART (ART_L) group, medium-dose ART (ART_M) group, and high-dose ART group (ART_H). CSVD rat models were established through bilateral common carotid artery occlusion (BCCAO). Subsequently, the rats were further divided into four groups: the empty plasmid control group (shNC) and three groups receiving NLRP3-shRNA interference plasmids (shNLRP3-1, shNLRP3-2, shNLRP3-3). We recorded animal behaviors and stained nerve cell changes. Hippocampal expression levels of Caspase-1, cleaved caspase-1, IL-18, IL-1β, GSDMD-N, β-actin, and NLRP3 were evaluated in each group. Our findings revealed that ART ameliorated cognitive dysfunction and brain tissue injury in CSVD rats. Moreover, expression levels of cleaved caspase-1, IL-18, IL-1β, GSDMD-N, and NLRP3 in the hippocampus were significantly reduced in the shNLRP3 group, resulting in improved cognitive function in these rats. These results suggest that NLRP3 could be a potential therapeutic target in CSVD development in rats, and modulating its expression might mitigate pathological alterations associated with CSVD. Subsequently, lipopolysaccharide (LPS) was injected into the tail vein, and inflammatory factors in peripheral blood of rats were found to be increased, suggesting that the level of intracranial NLRP3 was increased. In addition, MWM experiment showed that after the increase of NLRP3 expression, the repair effect of ART on learning and memory dysfunction was weakened. ART may enhance cognitive impairment in CSVD rats by downregulating NLRP3 expression in the brain, thereby inhibiting neuronal cell pyroptosis in the hippocampus.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"160"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologically activating BDNF/TrkB signaling exerted rapid-acting antidepressant-like effects through improving synaptic plasticity and neuroinflammation.","authors":"Si-Rui Sun, Jia-Ning Zhao, Peng-Wei Bi, Hui-Ying Zhang, Guang-Xiang Li, Jiao-Zhao Yan, Yun-Feng Li, Yong-Yu Yin, Hao Cheng","doi":"10.1007/s11011-025-01583-0","DOIUrl":"https://doi.org/10.1007/s11011-025-01583-0","url":null,"abstract":"<p><p>BDNF (Brain-derived neurotrophic factor)/TrkB (tropomyosin receptor kinase B) signaling has great therapeutic potential for depression, but the underlying mechanism remains unclear. This study aims to investigate the molecular mechanism underlying the BDNF/TrkB signaling-mediated antidepressant effects. Chronic Cort drinking for 4 weeks and a single injection of LPS for 24 h were used to induce depression-like behaviors; this study used 7,8-dihydroxyflavone (7,8-DHF, 10 mg/kg, i.p.), a selective TrkB receptor agonist, to activate the BDNF/TrkB signaling and examined its rapid-acting antidepressant-like effects; levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in BV2 microglial cells and synapse-related factors (BDNF, GluA1, Synapsin-1, and PSD95) in HT22 cells were examined by ELISA. Our behavioral results suggested that 7,8-DHF (10 mg/kg, i.p.) exerted rapid-acting antidepressant-like effects in Cort/LPS-treated mice; our immunofluorescence staining results suggested that Cort/LPS reduced the number of NeuN + HT22 cells and increased the number of Iba1 + BV2 microglial cells, which were completely reversed by 7,8-DHF pre-treatment. Our ELISA results suggested that 7,8-DHF significantly normalized the release of synapse-related factors (BDNF, GluA1, and PSD95) in HT22 cells and suppressed the production of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in BV2 microglial cells. Taken together, this study suggested that pharmacologically activating the BDNF/TrkB signaling pathway exerted rapid-acting antidepressant-like effects through improving synaptic plasticity and inhibiting neuroinflammation, which provided new insights for developing next-generation rapid-acting antidepressants.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"158"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium butyrate alleviates spinal cord injury via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis.","authors":"Yanru Cui, Qiuyu Cen, Jing Feng, Juanfang Wei, Linjie Wang, Cong Chang, Rizhao Pang, Junyu Wang, Anren Zhang","doi":"10.1007/s11011-025-01589-8","DOIUrl":"10.1007/s11011-025-01589-8","url":null,"abstract":"<p><p>NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase 1 (Caspase-1)/gasdermin D (GSDMD)-mediated pyroptosis is linked to spinal cord injury (SCI) pathogenesis. The levels of short-chain fatty acids (SCFAs), especially butyric acid, are significantly altered after SCI. Sodium butyrate (NaB) has anti-inflammatory effects on SCI; however, its effect on pyroptosis is unknown. The aim of this study was to determine the role of NaB in SCI functional recovery and its effect on NLRP3/Caspase-1/GSDMD-mediated pyroptosis. SCI model rats were established using aneurysm clips. After SCI, rats were administered NaB (300 mg/kg) via gavage. SCFAs in faeces were measured using gas chromatography-mass spectrometry. Motor function recovery was assessed using cylinder rearing and grooming tests. Histopathological analysis was performed using haematoxylin-eosin staining, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick-end labelling. The expression of proteins associated with pyroptosis signalling pathways was analysed using enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. SCFAs levels, particularly butyric acid, significantly decreased after SCI. NaB treatment promoted forelimb motor function recovery and attenuated pathological SCI. NaB also decreased spinal pro-inflammatory factors (interleukin-18 and interleukin-1β) and downregulated pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein, Caspase-1, and GSDMD. NaB inhibits NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis and inflammation, exerting protective and therapeutic effects in SCI, suggesting NaB as an effective SCI treatment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"157"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STC2 regulates the proliferation, migration and glycolysis of glioma cells through modulating ITGB2.","authors":"Zefeng Wei, Dengfeng Ge, Jie Bu, Xuenan Wang, Tao Zhong, Xiaoxiao Gongye, Bin Zhang, Feng Yan, Chunyan He, Runhan Guo, Jiayi Li, Zhenzhen Jin","doi":"10.1007/s11011-025-01571-4","DOIUrl":"https://doi.org/10.1007/s11011-025-01571-4","url":null,"abstract":"<p><p>Glioma is a common and aggressive primary malignant brain tumor. However, the progression mechanism of glioma has not been well revealed. In this study, we intend to detect the function and related mechanism of STC2 in glioma. Gene Expression Profiling Interactive Analysis database was used to detect STC2 and ITGB2 expression in glioma samples, as well as the relationship between STC2 and other genes. The relationship between STC2 and ITGB2 was confirmed by co-immunoprecipitation assay. The biology function of glioma cells was determined by cell counting kit-8, colony formation, transwell, ELISA and western blot assays. We discovered that STC2 was highly expressed in glioma samples and cell lines. Knocked down of STC2 inhibited cell proliferation, invasion, migration and glycolysis. Further analysis demonstrated the interaction between ITGB2 and STC2 as well as its involvement in STC2-regulated proliferation, invasion, migration and glycolysis. In summary, our data afforded novel insights into understanding the regulatory mechanism of STC2 and suggested that the STC2/ITGB2 axis might be a potential therapeutic target for glioma.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"156"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective mechanism of apigenin in proton pump inhibitor-associated progressive cognitive impairment in adult zebrafish via targeting GSK-3β pathway.","authors":"Anjalee Bhratee, Dhrita Chatterjee, Romanpreet Kaur, Shamsher Singh","doi":"10.1007/s11011-025-01579-w","DOIUrl":"https://doi.org/10.1007/s11011-025-01579-w","url":null,"abstract":"<p><p>Cognitive impairment is characterized by memory loss and difficulty in focusing, remembering, adhering to directions, and solving problems; commonly seen in an elderly population. Apigenin (APG) (4', 5, 7-trihydroxyflavone) is a flavonoid with several positive health benefits, including chemoprevention, antioxidant and can suppress inflammatory responses by inhibiting TNF-α and IL-1β levels. In this experimental study, we observed the possible neuroprotective effects of APG in the zebrafish model exposed to Lansoprazole (LPZ), a proton pump inhibitor known to induce cognitive impairment through hyperactivation of GSK-3β pathway. This experiment involves 12 adult zebrafish per group, where one group received LPZ (100 mg) as a toxin for 7 days and APG (25, 50, and 100 mg/kg) as treatment, while DPZ (5 mg/kg) served as a standard comparison over the same period. Neurobehavioral tests such as T-Maze, Novel Tank Test (NTT), and Novel Object Recognition (NOR) were performed. Several biochemical assessments were also performed to evaluate the level of lipid peroxidation (LPO), glutathione (GSH), nitrite (NO), acetylcholinesterase activity (AChEs), catalase activity, neurotransmitters (GABA and glutamate), neuroinflammatory markers (IL-1β, TNF-α, and IL-10), and histopathological analysis. The results showed that apigenin enhanced memory function, improved neurotransmitter balance, decreased oxidative stress markers, regulated the production of proinflammatory cytokines, and inhibited GSK-3β activity. Additionally, the co-administration of a GSK-3β inhibitor further promoted neuroprotection and cognitive enhancement facilitated by apigenin, highlighting the importance of the GSK-3β signaling pathway. These findings highlight the potential of apigenin as a natural compound for mitigating cognitive dysfunction. However, this study should also include long-term toxicity assessments and deeper molecular analysis to elucidate Apigenin's mechanism of action fully. Future research should address these gaps to validate its therapeutic potential.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"155"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Indole 3-carbinol against Scopolamine-Induced cognitive and memory impairment in rats: modulation of oxidative stress, inflammatory and cholinergic pathways.","authors":"Laksmi Anusha Vinjavarapu, Srikanth Yadava, Harikrishna Reddy Dontiboina, Guntupalli Chakravarthi, Ramakrishna Kakarla","doi":"10.1007/s11011-025-01577-y","DOIUrl":"https://doi.org/10.1007/s11011-025-01577-y","url":null,"abstract":"<p><p>Indole 3-carbinol (I3C), a natural compound found in cruciferous vegetables, has demonstrated neuroprotective effects by modulating oxidative stress, inflammation, and cholinergic pathways. This study aimed to evaluate the efficacy of I3C in preventing cognitive impairment induced by scopolamine in rats. Male Wistar rats were assigned to six groups: Control, Scopolamine (1 mg/kg), I3C (25 mg/kg), I3C (50 mg/kg), I3C (100 mg/kg), and Donepezil (5 mg/kg). Memory function was evaluated through behavioral assessments using the Y-maze and Novel Object Recognition (NOR) tests. Biochemical analyses were conducted to assess acetylcholinesterase (AChE) activity and oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). ELISA were utilized to quantify oxidative stress regulators (NRF2 and HO-1), inflammatory cytokines (NF-kB, TNF-α, IL-6, and IL-10), and apoptosis-related markers (Cytochrome C, caspase 9, and caspase 3). Additionally, H&E and Nissl staining were performed to evaluate histopathological abnormalities. The findings revealed that I3C administration markedly enhanced cognitive performance in the Y-maze and NOR tests, which were attributed to decreased AChE activity and increased acetylcholine (ACh) levels. Furthermore, I3C significantly alleviated oxidative stress by upregulating antioxidant enzymes, including NRF2 and HO-1. Moreover, I3C mitigated inflammatory responses, as evidenced by elevated levels of IL-10 and reduced levels of NF-kB, TNF-α, and IL-6. These findings indicate that I3C exhibits neuroprotective effects by reducing oxidative stress, suppressing inflammation, and addressing abnormalities in the cholinergic pathway, highlighting its potential as a therapeutic approach for alleviating cognitive deficits.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 4","pages":"154"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}