Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

{"title":"6-gingerol Attenuates Inflammatory Response in Rats With Spinal Cord Injury by Reducing NLRP3-mediated Microglial Pyroptosis.","authors":"Junjie Li, Jinfeng Hu, Shuhan Liang, Jinxin Luo, Yaojian Rao","doi":"10.1007/s11481-026-10311-z","DOIUrl":"10.1007/s11481-026-10311-z","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe neurological disorder with limited therapeutic options. 6-gingerol, a major bioactive component of ginger, possesses anti-inflammatory and neuroprotective activities; however, its role in SCI remains incompletely understood. This study investigated the effects and underlying mechanisms of 6-gingerol in SCI-induced microglial pyroptosis. A rat SCI model was established and treated with 6-gingerol. Neurological function, histopathological changes, microglial activation, and pyroptosis were evaluated. An LPS/ATP-induced BV2 microglial pyroptosis model was used for in vitro mechanistic studies. Cell viability, LDH, pyroptosis-related proteins, and inflammatory cytokines were analyzed. The expression of EZH2, USP7, and FOXO3 was determined by qRT-PCR and Western blot. Chromatin immunoprecipitation was performed to evaluate EZH2 and H3K27me3 mediated regulation of the USP7 promoter, while co-immunoprecipitation and ubiquitination assays were used to examine the interaction between USP7 and FOXO3. 6-gingerol significantly improved locomotor recovery, attenuated spinal cord tissue damage, and reduced microglial pyroptosis and inflammatory response after SCI. Mechanistically, 6-gingerol suppressed EZH2 expression and reduced H3K27me3 enrichment at the USP7 promoter, thereby restoring USP7 expression. Increased USP7 enhanced FOXO3 deubiquitination and stabilization, leading to suppression of pyroptotic signaling. Furthermore, EZH2 overexpression, USP7 inhibition, or FOXO3 knockdown partially abolished the anti-pyroptotic effects of 6-gingerol in vitro, and EZH2 overexpression attenuated the neuroprotective effects of 6-gingerol in SCI rats. In conclusion, 6-gingerol treatment alleviates SCI-induced neuroinflammation and microglial pyroptosis through the EZH2/USP7/FOXO3 axis, highlighting a potential therapeutic strategy for SCI.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867099","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":"Palmitic Acid Amplifies Microglial Inflammatory Activation Involving C5aR1-Sensitive Inflammatory Signaling and JMJD3/H3K27me3-Related Epigenetic Changes.","authors":"Liqing Chen, Sanqing Xu, Yan Liu, Xiaoping Luo","doi":"10.1007/s11481-026-10308-8","DOIUrl":"10.1007/s11481-026-10308-8","url":null,"abstract":"<p><p>Microglial pro-inflammatory activation contributes to neuroinflammatory processes in many neurological disorders. Saturated fatty acids such as palmitic acid (PA) are increasingly recognized as inflammatory cues, yet the molecular mechanisms linking PA to microglial inflammatory responses remain incompletely defined. In this study, using BV-2 microglia as an exploratory in vitro model, we investigated whether C5aR1-sensitive signaling and JMJD3/H3K27me3-related epigenetic changes are involved in PA-associated inflammatory responses. PA exposure increased Iba1 expression, altered CD86/CD206 expression, and enhanced the secretion of IL-1β, IL-6 and TNF-α. Exogenous C5a produced broadly similar inflammatory changes. Under heat-inactivated serum conditions, PA increased cell-associated C5a immunoreactivity and extracellular C5a levels, and these C5a-related readouts were reduced by PMX53. PMX53 also attenuated PA-associated increases in inflammatory markers and in the expression of TLR4, total NF-κB p65, c-Fos, and c-Jun. In parallel, PA and C5a increased JMJD3 expression and JMJD3 enrichment at selected IL-1β and IL-6 promoter regions, accompanied by reduced H3K27me3 enrichment at these loci. Pharmacological KDM6 inhibition with GSK-J4 attenuated PA-associated increases in IL-1β and IL-6 expression. Together, these findings support the involvement of C5aR1-sensitive inflammatory signaling and JMJD3/H3K27me3-related epigenetic regulation in PA-associated microglial inflammatory responses.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Pannexin2 Expression in Retinal Degeneration: Insights from the P23H Mouse Model of Retinis Pigmentosa.","authors":"Mateo Ruiz-Conca, Enola Missonnier, Estela Tébar-Garcerán, Marta Estalrich-Soliveres, Oksana Kutsyr, Eva Tudurí, Lorena Vidal-Gil, Natalia Martínez-Gil, Laura Fernández-Sánchez, Victoria Maneu","doi":"10.1007/s11481-026-10317-7","DOIUrl":"10.1007/s11481-026-10317-7","url":null,"abstract":"<p><p>Pannexins are large channels involved in purinergic signaling within the nervous system. However, their role in human disease and their therapeutic potential remain poorly understood, particularly for Pannexin-2 (Panx2). The aim of this study was to investigate whether Panx2 is associated with retinal neurodegenerative diseases. Using immunohistochemistry and flow cytometry, we analyzed Panx2 expression in the retina of the P23H mouse model of retinitis pigmentosa and in control C57BL/6J mice. We observed that healthy retinas contained a small population of Panx2-positive cells. In contrast, the Panx2 positive population was increased in the retinas of P23H retina, particulary at advanced stages of the disease. Panx2 was found to co-occur with the purinergic receptors P2X7R but not with P2X4R. This result was further supported by the reanalysis of RNA-seq data from GEO functional genomics data repository, which indicated an increased Panx2 mRNA expression in P23H mice at intermediate stages of the disease, compared with control animals. Together, these findings suggest that Panx2 expression is altered during retinal degeneration in the P23H model and may be associated with purinergic signaling pathways involved in disease progression. These results raise interesting questions for further investigation regarding the role of Panx2 in retinal degeneration.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820448","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":"Correction: Antioxidant‑Effective Quercetin Through Modulation of Brain Interleukin‑13 Mitigates Autistic‑Like Behaviors in the Propionic Acid‑Induced Autism Model in Rats.","authors":"Kubilay Doğan Kılıç, Gökçen Garipoğlu, Burak Çakar, Yiğit Uyanıkgil, Oytun Erbaş","doi":"10.1007/s11481-026-10310-0","DOIUrl":"10.1007/s11481-026-10310-0","url":null,"abstract":"","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Dose Cannabidiol Treatment does not Alter Cognitive Performance in the HIV-1 Transgenic Rat Model of NeuroHIV.","authors":"Samantha M Ayoub, Sunitha Vemuri, Arpi Minassian, Jared W Young","doi":"10.1007/s11481-026-10309-7","DOIUrl":"10.1007/s11481-026-10309-7","url":null,"abstract":"<p><strong>Background: </strong>HIV-associated neurocognitive impairment (NCI) remains prevalent among virally suppressed people living with HIV (PLWH) and approved treatments target these symptoms. Cannabidiol (CBD), a non-intoxicating cannabinoid with neuroprotective and anti-inflammatory properties, has been proposed as a potential therapeutic candidate for HIV-associated NCI, yet its cognitive effects in the context of HIV have not been experimentally tested.</p><p><strong>Methods: </strong>Female and male HIV-1 transgenic (HIV-1Tg; n = 57) and Fischer 344 (F344; n = 57) control rats were assessed using a translational cognitive battery measuring risk-based decision-making (Iowa Gambling Task; IGT), learning and cognitive flexibility (Probabilistic Reversal Learning Task; PRLT), and effortful motivation (Progressive Ratio Breakpoint Task; PRBT). Animals were tested at baseline to establish innate cognitive performance, then retested following acute and chronic (16-day) CBD administration (0, 0.3, and 3 mg/kg).</p><p><strong>Results: </strong>HIV-1Tg rats exhibited subtle IGT deficits and persistent reversal learning deficits in the PRLT, with preserved learning and motivation, modeling key features of HIV-associated NCI. These selective impairments in cognitive flexibility persisted across testing periods, with performance in other domains largely intact. CBD produced modest, dose-specific effects on response latencies and motivation but did not affect cognitive performance.</p><p><strong>Conclusion: </strong>HIV-1Tg rats exhibited selective cognitive deficits similar to those seen in PLWH, supporting their utility as a preclinical model of HIV-associated NCI. Across multiple translatable cognitive domains CBD did not significantly alter cognitive performance in HIV-1Tg rats at the doses tested. Further research using broader dosing, different administration routes, and co-administration with other cannabinoids is needed to fully explore the therapeutic potential of CBD for targeting HIV-associated NCI.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802614","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":"Crosslink Between Neuroinflammation and Oxidative/Nitrosative Status in the Glioblastoma Tumor Microenvironment: Prognostic and Theranostic Impact.","authors":"Narimene Beder, Mourad Belkhelfa, Lynda Hassani, Yamina Yousfi, Amina Adel, Toufik Selmane, Souhil Tliba","doi":"10.1007/s11481-026-10313-x","DOIUrl":"10.1007/s11481-026-10313-x","url":null,"abstract":"<p><p>Glioblastoma (GB) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor prognosis. Increasing evidence suggests that oxidative and nitrosative stress, together with a proinflammatory tumor microenvironment (TME), play a critical role in gliomagenesis. In this study, we analyzed a cohort of 89 Algerian patients with GB glioblastoma, to characterize systemic and intratumoral oxidative/ nitrosative status. Hydrogen peroxide, malondialdehyde, total nitrite levels, and catalase activity were quantified in serum or plasma, cystic fluid, and tumor homogenates to assess redox balance across different histological glioblastoma subtypes. In parallel, tumor expression of proinflammatory cytokines: interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and key mediators of tumor progression: Nuclear factor kappa B p65 (NF-κB p65), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF), was evaluated. Additionally, we investigated the interplay between redox balance and inflammatory signaling, and its potential implications for prognosis and theranostic therapeutic decision-making. Our findings demonstrated systemic and intratumoral redox imbalance in serum/ plasma compared with TME tumor microenvironment compartments, without impact from any subtypes. However, we noted pronounced intratumoral proinflammatory cytokines expression, as well as NF-κB p65, iNOS and VEGF in most cases, consistent with ongoing neuroinflammatory signaling, a highly reactive TME and more aggressive histopathological features. Combined assessment of oxidative/ nitrosative stress biomarkers and proinflammatory cytokines provides valuable insight into GB glioblastoma prognostic relevance. Targeting redox imbalance and inflammatory pathways within the GB glioblastoma TME represents a promising strategy to enhance therapeutic efficacy and improve patient outcomes.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802603","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":"Sequence Variation of Epstein-Barr Virus EBNA-1 Gene in Central Nervous System Inflammatory Demyelinating Diseases in Pakistan.","authors":"Ayesha Munir, Sanaullah Khan, Hira Nusrat, Ijaz Ali","doi":"10.1007/s11481-026-10312-y","DOIUrl":"10.1007/s11481-026-10312-y","url":null,"abstract":"<p><p>CNS inflammatory demyelinating diseases (CNS-IDDs), including multiple sclerosis and related conditions, have increasingly been associated with Epstein-Barr virus (EBV). However, data on EBV genetic diversity, particularly regarding EBNA-1 gene variants, across different CNS-IDD subtypes in South Asian populations remain limited. This study examined EBV DNA prevalence and EBNA-1 sequence variation in 40 patients with CNS-IDD and 40 healthy controls from Pakistan. EBV DNA was found in 21 of 80 samples (26%), with a significantly higher occurrence in CNS-IDD patients (16/40, 40%) compared to healthy controls (5/40, 13%) (p = 0.005, OR = 4.667). All EBV-positive samples clustered within the P-thr EBNA-1 variant, carrying consistent amino acid substitutions P476Q, A487T, S492C, and T524I, suggesting these are conserved features of the regionally circulating strain. These findings provide a foundation for further studies to explore the pathogenic significance of EBNA-1 variation linked with CNS-IDDs in the region.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763056","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":"cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.","authors":"Abdul Rahim, Shaik Mahammad Zubair, Mustak Ahamed, Soumi Das, Royal Patel, Biplab Debnath, Pratyush Porel","doi":"10.1007/s11481-026-10307-9","DOIUrl":"10.1007/s11481-026-10307-9","url":null,"abstract":"<p><p>The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an essential cytosolic DNA-sensing system that plays an important role in the regulation of innate immune and inflammatory responses in the central nervous system (CNS). It was first discovered as a promising antiviral defense cascade and has since been shown to execute broader functions in neuroinflammation and neurodegeneration. The pathway can become hyperactive with the release of endogenous DNA from damaged nuclei, mitochondria, or genomic instability, leading to chronic production of type I interferon (TI-IFN), various pro-inflammatory cytokines, and eventually contributing to chronic neuroinflammatory diseases. Recent studies have found that dysregulated cGAS-STING signaling is associated with several neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), stroke, and age-related neurodegeneration. In the CNS, chronic activation of this pathway leads to activation of microglia, oxidative stress, breakdown of the blood-brain barrier (BBB), impaired function of the synapses, and neuronal death. Mitochondrial dysfunction and cytosolic release of mitochondrial DNA (mtDNA) further promote inflammatory signaling, thus perpetuating neurodegeneration. This review highlights the molecular and pathological mechanisms of cGAS-STING signaling in a broader aspect of neurological disorders and appraises the novel therapeutics already under development to inhibit this pathway to regulate neuroinflammation and enhance neurological outcomes.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714915","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":"Inhibition of GPR4 Ameliorates Neuropathic Pain and Neuronal Ferroptosis via Regulation of Spinal RhoA/YAP Signaling in Rats.","authors":"Shuguang Yang, Longqing Zhang, Wei Mei","doi":"10.1007/s11481-026-10305-x","DOIUrl":"10.1007/s11481-026-10305-x","url":null,"abstract":"<p><p>Neuropathic pain is a chronic pain disorder refractory to conventional analgesics. Iron-dependent neuronal ferroptosis has been implicated in its pathogenesis. G protein-coupled receptor 4 (GPR4), a proton-sensing receptor, is involved in inflammation and ferroptosis, but its role in neuropathic pain and spinal neuronal ferroptosis remains unclear. Neuropathic pain was induced in rats using the spared nerve injury (SNI) model, and GPR4 expression and its effects on pain behaviors, neuronal ferroptosis, and spinal inflammation were examined. GPR4 was inhibited by a selective antagonist or small interfering RNA (siRNA), while Ras homolog family member A (RhoA) and Yes-associated protein (YAP) were activated via intrathecal injection of specific agonists. Spinal GPR4 expression was significantly upregulated and neuronal ferroptosis was induced by SNI, as evidenced by increased iron accumulation, lipid peroxidation, and dysregulated ferroptosis-related protein expression. SNI-induced mechanical allodynia, cold hyperalgesia, neuronal ferroptosis, and spinal inflammation were attenuated by GPR4 inhibition or knockdown. Mechanistically, the spinal RhoA/YAP signaling pathway was activated by SNI, and this activation was reversed by GPR4 inhibition. Furthermore, the analgesic and anti-ferroptotic effects of GPR4 inhibition were abolished by RhoA or YAP activation. It is demonstrated that GPR4 regulates neuropathic pain, neuronal ferroptosis, and spinal inflammation via the spinal RhoA/YAP signaling pathway, suggesting that GPR4 inhibition may represent a promising novel therapeutic strategy for neuropathic pain.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698301","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":"Aurantio-Obtusin Attenuates Aβ-Induced Cognitive Impairment and Synaptic Dysfunction by Suppressing Neuroinflammation in Mice.","authors":"Xueying Feng, Wei Yu, Song Guo, Yanyan Ji, Junhua Li, Ling Wang, Guolu Zhong, Shiyi Li, Linlin Niu, Danxin Zhu, Kan Zhou, Yehong Du","doi":"10.1007/s11481-026-10306-w","DOIUrl":"10.1007/s11481-026-10306-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD) features Aβ-driven neuroinflammation and synaptic dysfunction that converge on cognitive decline, underscoring the potential value of multi-target interventions. Aurantio-obtusin (AO), a bioactive anthraquinone from Cassia obtusifolia L., exhibits reported anti-inflammatory and antioxidant activities; however, whether AO counteracts Aβ-associated behavioral impairment through coordinated modulation of inflammatory and synaptic alterations remains unclear. Here, we investigated whether AO alleviates Aβ₁₋₄₂-induced cognitive deficits and examined synapse- and inflammation-related molecular correlates. Male C57BL/6 mice received intracerebroventricular Aβ₁₋₄₂ to establish an acute AD-like model and were treated with AO (10 mg/kg/day, oral gavage) for consecutive weeks. The results showed that AO improved spatial learning and memory in the Morris water maze, recognition memory in the novel object recognition test, and working memory in the Y-maze, without affecting spontaneous locomotor activity. Furthermore, AO alleviated synaptic dysfunction by restoring synaptophysin expression and upregulating GAD65, and mitigated neuroinflammation by elevating anti-inflammatory factors (IL-4, IL-10, ARG1) and reducing TNF-α. In vitro experiments confirmed that AO was non-cytotoxic to N2A^APP cells across 0-80 μM, mildly downregulated BACE1 expression, and suppressed the Aβ-induced upregulation of pro-inflammatory mediators (IL-6, iNOS) in BV2 microglial cells. Overall, AO attenuated Aβ_1-42-driven behavioral impairment in parallel with improvements in synapse-associated markers and inflammatory readouts. These findings support further evaluation of AO as a natural compound associated with modulation of Aβ-related neuroinflammatory and synapse-associated alterations.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681470","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}