Inflammopharmacology最新文献

{"title":"Quercetin protects against neuronal toxicity by activating the PI3K/Akt/GSK-3β pathway in vivo models of MPTP-induced Parkinson's disease.","authors":"Yajuan Li, Minghao Man, Yiyuan Tian, Gang Zhao, FengZhou Liu, JingYu Zhao, Songya Huang, Junhui Xue, Wei Chang","doi":"10.1007/s10787-025-01712-2","DOIUrl":"https://doi.org/10.1007/s10787-025-01712-2","url":null,"abstract":"<p><strong>Background: </strong>Quercetin is a flavonoid commonly found in various fruits, vegetables, and grains. Studies have demonstrated that quercetin may help protect neuronal cells from damage caused by neurotoxins associated with Parkinson's disease, however, the underlying mechanism remains unclear.</p><p><strong>Aim: </strong>The current study aimed to investigate the neuroprotective effects of quercetin in MPTP-induced Parkinson's disease mouse models and elucidate its mechanistic role in modulating the PI3K/Akt/GSK-3β signaling pathway.</p><p><strong>Materials and methods: </strong>Male C57BL/6 mice were divided into control, MPTP, quercetin, and MPTP + quercetin groups. The protective effects of quercetin on Parkinson's disease in mice were evaluated using animal behaviour analysis, histopathological examination, and immunofluorescence staining. Subsequently, network pharmacology was utilized to determine the primary target sites of quercetin in Parkinson's disease. Finally, western blotting and molecular docking techniques were applied to validate the identified targets.</p><p><strong>Results: </strong>Quercetin significantly improved motor deficits in MPTP mice, reduced neuronal atrophy, and preserved TH⁺ dopaminergic neurons. Western blotting analysis revealed quercetin upregulated anti-inflammatory IL-10 (p < 0.01) and TGF-β (p < 0.01) while suppressing pro-inflammatory IL-1β (p < 0.01) and iNOS (p < 0.01). It activated the PI3K/Akt/GSK-3β pathway by increasing phosphorylation of PI3K (p < 0.01), Akt (p < 0.01), and GSK-3β (p < 0.01). Quercetin also elevated anti-apoptotic Bcl-2 (p < 0.01) and reduced pro-apoptotic Bax (p < 0.01) and Caspase-9 (p < 0.01). Molecular docking confirmed strong binding between quercetin and PI3K/Akt/GSK-3β (binding energies: -6.44 to -5.24 kcal/mol).</p><p><strong>Conclusion: </strong>Quercetin alleviates Parkinson's disease pathology by inhibiting neuroinflammation, reducing apoptosis, and activating the PI3K/Akt/GSK-3β pathway. These findings underscore its potential as a multi-target therapeutic agent for Parkinson's disease.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ceramide: a central regulator in Alzheimer's disease pathogenesis.","authors":"Priyanka Choudhary, Shilpa Kumari, Kajal Bagri, Rahul Deshmukh","doi":"10.1007/s10787-025-01719-9","DOIUrl":"https://doi.org/10.1007/s10787-025-01719-9","url":null,"abstract":"<p><p>Ceramide is a key component of sphingolipid metabolism and functions as a lipid second messenger. Sphingolipids are crucial for maintaining the nervous system, particularly in differentiation and development. Ceramide supports hippocampal growth but, at elevated levels, can impair dendritic cell function. During aging and neurodegenerative diseases like Alzheimer's disease (AD), intracellular ceramide production and accumulation increase, negatively impacting cognitive functions. High ceramide levels are linked to the progression of AD pathology, significantly contributing to amyloid β (Aβ) accumulation, tau tangle formation, insulin resistance, oxidative stress, and neuroinflammation. Ceramide facilitates the production and aggregation of Aβ peptides, leading to neurotoxic plaque formation. Its dysregulation is associated with abnormal tau protein phosphorylation, resulting in neurofibrillary tangles (NFTs). In addition, elevated ceramide levels can trigger brain inflammation by promoting the release of pro-inflammatory cytokines and activating microglia. This accumulation also enhances oxidative stress in neurons, damaging cellular components such as proteins, lipids, and DNA. This review will help in deeper understanding of the molecular pathways altered via ceramide metabolism and accumulation involved in the AD pathology. The cellular and pathological mechanisms of ceramide and their impact on Alzheimer's disease pathophysiology. A deeper understanding of ceramide-mediated effects in aging and AD could pave the way for innovative therapeutic strategies targeting ceramide metabolism to treat neurodegenerative diseases and age-related cognitive decline.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carnosol mitigates Ang II-stimulated vascular injury and oxidative stress by directly binding to FAK and inhibiting its activation.","authors":"Yucheng Jiang, Zhaozheng Zheng, JunYi Wang, Yingjie Liao, Zhihan Jia, Wante Lin, Diyun Xu, Jiong Wang, Gaojun Wu, Guang Liang, Bozhi Ye","doi":"10.1007/s10787-025-01721-1","DOIUrl":"https://doi.org/10.1007/s10787-025-01721-1","url":null,"abstract":"<p><p>Vascular injury is a serious complication associated with hypertension, for which effective treatments are currently lacking. Oxidative stress serves as the primary pathophysiological mechanism underlying hypertension-induced vascular injury. Carnosol, an extract derived from rosemary, has garnered increasing interest because of its well-established antioxidant properties. However, its potential therapeutic effect on vascular injury remains unclear. This study investigated the therapeutic potential of carnosol in angiotensin II-stimulated vascular injury and elucidated its underlying mechanisms of action. C57BL/6J mice were subjected to vascular injury through the subcutaneous implantation of a micropump filled with Ang II, followed by the intragastric administration of carnosol for four weeks. Carnosol ameliorated Ang II-stimulated vascular dysfunction and remodeling in a dose-dependent manner. Mechanistically, carnosol exerted an inhibitory effect on oxidative stress in the vascular tissue and HUVECs by regulating the PI3K/AKT pathway. Furthermore, we revealed that FAK, which received the highest target score in the molecular docking analysis, could directly bind to carnosol in both cellular models and human aortic tissues. Additionally, carnosol inhibited the phosphorylation of FAK, thereby reducing oxidative stress levels in HUVECs. Notably, when PND-1186 was administered to inhibit the phosphorylation of FAK, carnosol was no longer able to modulate the PI3K/AKT signaling pathway. In conclusion, we showed that carnosol can inhibit the PI3K/AKT signaling pathway by binding to the FAK protein and reducing its phosphorylation, thereby improving Ang II-stimulated vascular injury.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endotoxin (lipopolysaccharide)-induced inflammation in albino rat and macrophages (RAW 264.7): Piper mullesua leaf extract as promising therapeutic against inflammatory pathophysiology via SOCS1 activation and phospho-NF-κB/JAK1/STAT1 inhibition.","authors":"Rikraj Loying, Laikangbam Lamyanba, Anupriya Borah, Reparani Thokchom, Vekuno Cukhamu, Hiranmoy Barman, Bhaben Sharmah, Nazim Uddin Afzal, Mir Ekbal Kabir, Archana Moni Das, Jatin Kalita, Pulok Kumar Mukherjee, Nanaocha Sharma, Prasenjit Manna","doi":"10.1007/s10787-025-01713-1","DOIUrl":"https://doi.org/10.1007/s10787-025-01713-1","url":null,"abstract":"<p><p>The present investigation has been attempted for scientifically validating the traditional uses of Piper mullesua against inflammatory pathophysiology using both in vivo (albino rats) and in vitro (macrophage cells, RAW 264.7) models of inflammation caused by an endotoxin (lipopolysaccharide, LPS). Oral gavaging with PMHAE, hydroalcoholic extract of Piper mullesua leaves, dose-responsively (50, 100, or 200 mg/kg BW, 14 days) restored any alteration in the concentration of serum inflammatory cytokines, IL-6, TNF-α, IL-4, and IL-10 and decreased prostaglandin (PGE2) and nitrite count in rats injected (i.p.) with LPS (10 mg/kg BW). PMHAE supplementation (5, 10, or 20 µg/mL) further attenuated MCP-1, IL-6, and TNF-α, and increased IL-10 and IL-4 secretion and mRNA expression in LPS-treated (50 ng/mL) macrophages. PMHAE also enhanced phagocytic potential while attenuated ROS counts in LPS-treated cells. Additionally, PMHAE supplementation increased SOCS1 protein expression and decreased NF-κB phosphorylation (Serine 536), along with the expression of JAK1/STAT1 proteins in LPS-treated cells. Treatment with PMHAE did not cause any toxicity to animals and cultured cells. Phytochemical analysis (LC-MS/GC-MS) revealed various compounds, including piperine, piperlongumine, pipernonaline, phytol, methyl eugenol, and pinene, contributing to anti-inflammatory potential of PMHAE. These findings suggested Piper mullesua as a safe, effective, and potential anti-inflammatory avenue for therapeutic exploration in inflammatory pathophysiology.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory properties of a methanolic extract of Ficus lyrata mitigate inflammation in Complete Freund's Adjuvant-induced arthritis.","authors":"Anam Iftikhar, Mohammad Saleem, Syed Atif Raza, Adrian Achuthan, Rodney Luwor, Taha Muhammad, Umair Majeed","doi":"10.1007/s10787-025-01700-6","DOIUrl":"https://doi.org/10.1007/s10787-025-01700-6","url":null,"abstract":"<p><p>Ficus lyrata, renowned for its traditional use in alleviating rheumatic pain and inflammation, was validated for its purported anti-arthritic and antiinflammatory properties using InvivoandInvitromodels. In the in-vivo studies, carrageenan-induced acute oedema and a chronic arthritis induced by complete Freund's adjuvant (CFA) were employed. Oral dosing of methanolic extract from Ficus lyrata (m-FL) was administered at (250,500 and 750 mg/kg) as well as methotrexate at 1 mg/kg, significantly (p < 0.0001) demonstrated a dose dependent decrease in percent oedema/inflammation and notably reduced arthritis development in the CFA model, indicating strong anti-inflammatory effects over time. Further analysis revealed m-FL extract inhibited protein denaturation across all evaluated concentrations(1600,800,400,200,100,50 µg/ml) suggesting potential mechanisms for their anti-inflammatory action. Phytochemical analysis identified flavonoids and phenolic compounds in the extract. Gene expression analysis of m-FL extract treatment group using qPCR showed a significant (p < 0.0001) downregulation of various inflammatory markers (IL1,COX2,IL1β, NFκB, TNF,STAT-3,IL6) with simultaneous upregulation in the expression of antiinflammatory markers (IL4,10). The m-FL extract targets TNF-mediated decrease in interleukins specifically IL-1, IL1β and IL-6. Histopathological assessments and radiographic evaluations conducted subsequently demonstrated a significant decline in joint inflammation, bone erosion, and pannus formation, along with improved bone integrity and reduced inflammation in the m-FL extract-treated groups (p < 0.0001). Although the m-FL extract exhibited relatively stronger antioxidant activity compared to ascorbic acid in-vitro, the primary efficacy lies in the potent immunomodulatory and anti-arthritic effects. The m-FL extract showed potential as an adjunct therapy for managing inflammatory conditions.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the neuroprotective potential of Jatropha humboldtiana leaves and its metabolic profiling by UPLC-MS/MS.","authors":"Paul Alan Arkin Alvarado-García, Marilú Roxana Soto-Vásquez, Ricardo D D G de Albuquerque, Fadia S Youssef, Reem M Diri, Mohamed L Ashour","doi":"10.1007/s10787-025-01707-z","DOIUrl":"https://doi.org/10.1007/s10787-025-01707-z","url":null,"abstract":"<p><p>This study aims to determine the phytochemical profile of Jatropha humboldtiana ethyl acetate fraction (EAFHJ) using UPLC-MS/MS and evaluate its neuroprotective potential via in vivo model. In vivo behavioral assays including elevated plus maze (EPM), forced swim test (FST), tail suspension test, and pentylenetetrazol (PTZ) assay were conducted in mice to evaluate the anxiolytic, antidepressant, and anticonvulsant effects. Pro- and anti-inflammatory cytokines were measured, and acute toxicity studies were performed to determine LD50. Thirty-three compounds were identified in EAFHJ, including phenolic acids, flavonoids, and coumarins. In the FST, EAFHJ reduced the immobility time to 131.50 ± 3.46 s at 100 mg/kg compared to 139.88 ± 4.58 s in the control group (p < 0.01). In the EPM, the group treated with 200 mg/kg of EAFJH spent 48.14% of the time in the open arms, compared to 31.30% of the control group (p < 0.05). In the PTZ trial, the latency to myoclonic seizures was 3.0 ± 0.5 min at 200 mg/kg of EAFHJ compared with 1.01 ± 0.5 min in the control group (p < 0.05). The LD50 of the EAFJH was greater than 5000 mg/kg, indicating low toxicity. Furthermore, a significant reduction in pro-inflammatory cytokine levels (IL-6, TNF-α, IL-1β) and an increase in anti-inflammatory cytokines (IL-10, IL-4) were observed. Thus, it was concluded that Jatropha humboldtiana exhibits a diverse phytochemical profile and promising anxiolytic, antidepressant, and anticonvulsant effects, likely mediated by a combination of neurotransmitter modulation and anti-inflammatory mechanisms. Further studies are required to elucidate the precise molecular pathways involved and explore its clinical potential.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative nanocarriers in arthritis therapy: the role of herbal cubosomes.","authors":"Kajal Chaudhary, Lubhan Singh, Pallavi Dinanath Rai","doi":"10.1007/s10787-025-01714-0","DOIUrl":"https://doi.org/10.1007/s10787-025-01714-0","url":null,"abstract":"<p><strong>Background: </strong>Both osteoarthritis (OA) and rheumatoid arthritis (RA) are long-lasting inflammatory disorders that impact the joints. While conventional treatments like NSAIDs and DMARDs are effective, they often have adverse side effects.</p><p><strong>Objective: </strong>The aim of this review is to explore the possibilities of using herbal treatments in treating the symptoms of arthritis, their stability and bioavailability. Traditional therapies often lead to adverse side effects, prompting a search for safer alternatives, particularly in herbal medicines. This review explores the innovative use of herbal cubosomes as advanced nanocarriers for arthritis therapy. Cubosomes, a type of self-assembled lipid nanoparticle, exhibit unique structural characteristics that enhance the delivery and bioavailability of encapsulated herbal compounds.</p><p><strong>Method: </strong>Access was gained to PubMed, Scopus database, Google Scholar and Web of Science for the literature search. The results were later screened according to the titles, abstracts, and availability of full texts.</p><p><strong>Results: </strong>The expository evaluation of the literature revealed that Key herbal components, such as Withania somnifera (Ashwagandha), Curcuma longa (Turmeric) and Boswellia serrata (Frankincense) are emphasized for their anti-inflammatory characteristics and possible advantages in managing arthritis. The herbal cubosomes enhance drug absorption, retention, and release kinetics in arthritic conditions. The difficulties in delivering and maintaining herbal substances are also discussed, with a focus on how nanotechnology can help get over these obstacles.</p><p><strong>Conclusion: </strong>Overall, the integration of herbal cubosomes in arthritis therapy presents a promising approach that could result in safer and more efficient treatment alternatives, warranting further research and clinical exploration.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between anti-inflammatory therapies and renal outcomes in patients with established cardiovascular disease or high cardiovascular risks: a meta-analysis of randomised controlled trials.","authors":"Wenfeng Yang, Zonglin Li, Chu Lin, Xiaoling Cai, Fang Lv, Wenjia Yang, Linong Ji","doi":"10.1007/s10787-025-01711-3","DOIUrl":"https://doi.org/10.1007/s10787-025-01711-3","url":null,"abstract":"<p><strong>Background: </strong>To assess the relationship between anti-inflammatory therapy and renal events risk in participants with cardiovascular risks or diagnosed cardiovascular disease (CVD).</p><p><strong>Methods: </strong>Literature searches were carried out in PubMed, Embase, clinicaltrial.gov and the Cochrane Central Register of Controlled Trials. Randomised controlled trials that were published from January 1995 to July 2024, compared anti-inflammatory therapy and placebo in participants at cardiovascular risks or with diagnosed CVD and with reports of renal outcomes were included. The results were shown as risk ratio (RR) and 95% confidence interval (CI).</p><p><strong>Results: </strong>In comparison to placebo, therapies targeting inflammation did not exhibit a significant association with the risk of composite renal outcomes (worsening of renal function, death due to kidney disease and end-stage renal disease) (RR = 0.89, 95% CI 0.40 to 1.99, I² = 0%). The risk of worsening of renal function (RR = 0.81, 95% CI 0.21 to 3.07, I² = NA), end-stage renal disease (RR = 0.94, 95% CI 0.31 to 2.85, I² = 0%), death due to kidney disease (RR = 3.00, 95% CI 0.12 to 73.56, I² = NA), chronic kidney disease (RR = 1.77, 95% CI 0.74 to 4.23, I² = 0%), chronic renal failure (RR = 1.70, 95% CI 0.56 to 5.15, I² = 61%) and acute kidney injury (RR = 1.16, 95% CI 0.95 to 1.42, I² = 0%) showed no significant difference between patients receiving anti-inflammatory therapy and placebo.</p><p><strong>Conclusion: </strong>Current evidence did not indicate associations between anti-inflammatory therapies and adverse renal events risks in patients with cardiovascular risks or established CVD. Future researches are needed to explore the renal effects of anti-inflammatory therapy.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the anti-anaphylaxis potential of natural products: A Review.","authors":"Aya H Eid, Eman S Zaki, Miral O Sabry, Riham A El-Shiekh, Samar S Khalaf","doi":"10.1007/s10787-025-01685-2","DOIUrl":"https://doi.org/10.1007/s10787-025-01685-2","url":null,"abstract":"<p><p>Allergies are a common health issue affecting many people around the world, especially in developed countries. They occur when the immune system overreacts to substances that are usually harmless. Some common allergic conditions include asthma, sinus infections, skin rashes, food allergies, hay fever, severe allergic reactions, eczema, swelling, and reactions to medications or insect stings. The causes of these allergies are complex and often linked to genetics, which can lead to heightened immune responses known as atopy. Throughout history, plant extracts have been used for various purposes, including medicine and food. In addition, their bioactive compounds show a wide range of beneficial effects, such as reducing allergic reactions, fighting oxidative stress, mast cell stabilizers, and lowering inflammation, highlighting their potential for treating various health conditions. Flavonoids and phenolic compounds are commonly used in anaphylaxis for their potent anti-inflammatory action. This review aims to promote the use of natural products as potential treatments for anaphylaxis. In addition, the discovery of new drugs derived from natural sources holds significant promise for the management of anaphylaxis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of the cognitive impairment associated with Alzheimer's disease by valproic acid: possible drug repurposing.","authors":"Mirna Ezzat Sedrak Sorial, Ragwa Mansour Abdelghany, Nesrine Salah El Dine El Sayed","doi":"10.1007/s10787-025-01695-0","DOIUrl":"https://doi.org/10.1007/s10787-025-01695-0","url":null,"abstract":"<p><p>Sporadic Alzheimer's disease is a progressive neurodegenerative disorder affecting the central nervous system. Its main two hallmarks are extracellular deposition of aggregated amyloid beta resulting in senile plaques and intracellular hyperphosphorylated tau proteins forming neuro-fibrillary tangles. As those processes are promoted by the glycogen synthase kinase-3 enzyme, GSK3 inhibitors may be of therapeutic value in SAD. GSK3 is also inhibited by the action of insulin on insulin signaling. Insulin receptor desensitization in the brain is hypothesized to cause inhibition of insulin signaling pathway that ultimately causes cognitive deficits seen in SAD. In extant research, induction of cognitive impairment is achieved by intracerebroventricular injection of streptozotocin-a diabetogenic compound that causes desensitization to insulin receptors in the brain leading to the appearance of most of the SAD signs and symptoms. Valproic acid -a histone deacetylase inhibitor and anti-epileptic drug-has been recently studied in the management of SAD as a possible GSK3 inhibitor. Accordingly, the aim of the present study is to explore the role of multiple VPA doses on the downstream effects of the insulin signaling pathway in ICV STZ-injected mice and suggest a possible mechanism of VPA action. ICV STZ-injected mice showed deficiency in short- and long-term memory as well as increased anxiety, as established by open field test, Modified Y-maze, Morris water maze, and elevated plus maze neurobehavioral tests.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}