Neurochemical Research最新文献

{"title":"Plumbagin Alleviates Social Behavior Deficits in a Valproic Acid Model of Autism by Reducing Glial Activation and Oxidative Stress in the Cerebellum","authors":"Nasrin Nosratiyan,&nbsp;Olia Hamzeh,&nbsp;Maryam Ghasemi-Kasman","doi":"10.1007/s11064-025-04425-8","DOIUrl":"10.1007/s11064-025-04425-8","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects multiple brain regions, including the cerebellum. It is characterized by behavioral alterations that significantly impact various aspects of patients’ lives. The present study was conducted to examine the anti-inflammatory, antioxidant, and neuromodulatory activities of plumbagin (PLB) in a valproic acid (VPA)-induced autism model. Pregnant rats received an intraperitoneal (i.p.) injection of VPA (600 mg/kg) on day 12.5 of pregnancy. After birth, offspring were orally administered different doses of PLB (0.25, 0.5, and 1 mg/kg) from days 7 to 35. Social interaction and preference were assessed via a three-chamber social assay. Hematoxylin‒eosin (H&amp;E) staining was performed to observe histopathological changes in the cerebellum. Moreover, astrocyte and microglial activation were evaluated by immunostaining. The gene expression levels of <i>Nrf2</i>, <i>HO-1</i>, <i>BDNF</i>, <i>SIRT1</i>, <i>IL-6</i>, <i>IL-1β</i>, <i>TNF-α</i>, and <i>TGF-β1</i> were evaluated via quantitative real-time PCR (qRT‒PCR). These findings revealed that PLB treatment significantly alleviates social impairments. PLB ameliorated the loss of Purkinje cells and the number of activated astrocytes and microglia in the cerebellum. PLB administration also upregulated the gene expression of <i>Nrf2</i>, <i>HO-1</i>, <i>BDNF</i>, <i>SIRT1</i>, and <i>TGF-β1</i> and downregulated the <i>IL-6</i> expression level. Overall, it seems that PLB diminishes autism-related damage in the cerebellum through neuromodulatory activities and attenuation of oxidative stress and inflammation. </p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090985","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":"Tanshinone IIA Promotes Functional Recovery After Spinal Cord Injury by Inhibiting Neuron and Oligodendrocyte Ferroptosis Through the GPX4/ACSL4 Axis","authors":"Luchun Xu,&nbsp;Guozheng Jiang,&nbsp;Shuyin Tan,&nbsp;Yukun Ma,&nbsp;Jiawei Song,&nbsp;Yushan Gao,&nbsp;Guanlong Wang,&nbsp;Jiaojiao Fan,&nbsp;Yongdong Yang,&nbsp;Xing Yu","doi":"10.1007/s11064-025-04414-x","DOIUrl":"10.1007/s11064-025-04414-x","url":null,"abstract":"<div><p>Spinal cord injury (SCI) induces severe functional impairments and involves intricate secondary injury mechanisms. Tanshinone IIA (TIIA), a key bioactive component of <i>Salvia miltiorrhiza</i>, exhibits neuroprotective potential, yet its role in ferroptosis regulation post-SCI remains undefined. This study explored the protective effects and underlying mechanisms of TIIA in SCI. In a rat SCI model, TIIA markedly enhanced hind limb motor function and preserved histopathological integrity while mitigating mitochondrial damage, ferroptosis, and oxidative stress. TIIA attenuated ferroptosis by reducing reactive oxygen species (ROS), malondialdehyde (MDA), and acyl-CoA synthetase long-chain family member 4 (ACSL4) while elevating glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase 4 (GPX4) levels. Mechanistically, TIIA suppressed ferroptosis through modulation of the GPX4/ACSL4 axis. The ferroptosis inducer RSL3 abrogated these protective effects, further validating this mechanism. These findings highlight the therapeutic potential of TIIA in SCI by targeting the GPX4/ACSL4 pathway to attenuate ferroptosis and promote functional recovery.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073702","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":"Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases","authors":"Kai Gao,&nbsp;Albert Cheung-Hoi Yu","doi":"10.1007/s11064-025-04418-7","DOIUrl":"10.1007/s11064-025-04418-7","url":null,"abstract":"<div><p>Astrocytes support neurons by maintaining health, regulating the environment, and aiding synaptic transmission, while glutamate is vital for excitatory signaling in learning and memory. The “glutamate-glutamine cycle,” verified by Hertz and Schousboe, illustrates the interaction between neurons and astrocytes in glutamate regulation. Recent studies show astrocytes not only manage glutamate levels but also influence synaptic activity through gliotransmission and contribute to brain energy via glutamate metabolism. Dysregulation of this signaling is linked to neurological disorders like epilepsy and Alzheimer’s. This mini-review will explore research progress on astrocytes and glutamate, highlighting glutamate’s role in brain function and disease.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074065","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":"Modelling Epilepsy Associated Alzheimer’s Disease Through Mitochondrial Complex-I Inhibition: Neurochemical and Therapeutic Perspectives","authors":"Arvinder Kaur,&nbsp;Rajesh Kumar Goel","doi":"10.1007/s11064-025-04413-y","DOIUrl":"10.1007/s11064-025-04413-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is comorbid condition in epilepsy. Mitochondrial dysfunction serves as a common disease mechanism. This study aimed to develop a new mouse of epilepsy-associated AD by inhibiting mitochondrial complex-I and exploring neurochemistry to identify therapeutic targets. Swiss albino mice were divided into naïve, corneal kindled (CK), and rotenone corneal kindled (RCK) groups. CK underwent epileptogenesis by using 6 Hz corneal kindling model (15 mA, 20 V, 6-Hz, 3 s for 15 days), while RCK underwent both epileptogenesis and mitochondrial dysfunction via rotenone administration (2.5 mg/kg, i.p daily). RCK mice exhibited generalised tonic-clonic seizures, cognitive deficits, oxidative stress, and Aβ/tau deposition. Neurochemical analysis showed increased glutamate, kynurenine, and reduced GABA, taurine, monoamines, antioxidants, and acetylcholinesterase activity. The RCK model replicates construct and face validity of both epilepsy and AD, may serve as a new model to investigate shared disease mechanisms and associated altered neurotransmitter as therapeutic approach.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944254","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":"Assessing Ecto-5’-Nucleotidase/CD73 Expression and Malignancy Parameters in Early- and Late- Passage C6 Glioma Cells","authors":"Fabiana M. Manica,&nbsp;Luis Felipe I. Campesato,&nbsp;Juliete Nathali Scholl,&nbsp;Elizandra Braganhol,&nbsp;Leticia S. Bergamin,&nbsp;Maria Isabel A. Edelweiss,&nbsp;Guido Lenz,&nbsp;Jean Sevigny,&nbsp;Fabrício Figueiró,&nbsp;Ana Maria O. Battastini","doi":"10.1007/s11064-025-04409-8","DOIUrl":"10.1007/s11064-025-04409-8","url":null,"abstract":"<div><p>Glioblastoma (GB) is a highly aggressive tumor characterized by its proliferative and invasive behavior. Ecto-5’-nucleotidase (e5NT/CD73), an enzyme that hydrolyzes extracellular AMP to adenosine, plays a pivotal role in cellular processes and has been involved in tumor progression, with its upregulation observed in several cancers. C6 glioma cells, widely used in GB research, exhibit changes in morphology and biochemical properties, depending on their passage number. This study investigates malignancy-related parameters in early-passage (EPC6) and late-passage (LPC6) C6 cells, highlighting the e5NT/CD73 expression and activity. The results presented here demonstrate that the LPC6 cells showed reduced CD73 expression and lower e5NT/CD73 AMPase activity compared to the EPC6 cells. Despite a higher proliferation rate in the LPC6 cells after two days of growth, Ki67 expression analysis revealed comparable proliferation between the two cell types at 5 and 10 days. Notably, the EPC6 cells showed enhanced proliferation in response to exogenous AMP, whereas the LPC6 cells did not. Furthermore, the EPC6 cells exhibited decreased adhesion but greater colony formation than the LPC6 cells. The LPC6 cells showed a significant reduction in migration, likely due to the loss of e5NT/CD73 migratory function. In the in vivo results, all the rats injected with EPC6 cells developed tumors displaying all the histopathological features of GB, whereas the LPC6 cells formed smaller tumors. Confirming the role performed by e5NT/CD73 in glioma progression, protein silencing significantly reduced tumor growth in vivo. These findings underscore the critical role of purinergic signalling in GB progression and emphasize the need for careful monitoring of passage number and e5NT/CD73 in in vitro experiments.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944253","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":"Anethole Ameliorates Scopolamine-Induced Memory Deficits and Neuronal Damage Through Antioxidant, Anti-Inflammatory, and Anticholinesterase Activities in Rats","authors":"Seyed Esmaeil Khoshnam,&nbsp;Alireza Sarkaki,&nbsp;Yaghoob Farbood,&nbsp;Amirhesam Keshavarz Zarjani,&nbsp;Mohammad Ghasemi Dehcheshmeh,&nbsp;Sadegh Moradi Vastegani","doi":"10.1007/s11064-025-04417-8","DOIUrl":"10.1007/s11064-025-04417-8","url":null,"abstract":"<div><p>Scopolamine-induced memory impairment is a well-established model for studying the therapeutic potential of novel compounds in the pathogenesis of Alzheimer’s disease (AD). This study aimed to evaluate the protective effects and underlying mechanisms of anethole against scopolamine-induced memory and cognitive disorders. Rats were treated with scopolamine (0.7 mg/kg, i.p.) for 14 consecutive days. Anethole (125, 250, and 500 mg/kg, i.g.) was administered one hour prior to scopolamine injection. Memory and cognitive performance were assessed using the Passive Avoidance Test (PAT) and the Novel Object Recognition Test (NORT). In addition, blood–brain barrier (BBB) permeability, brain water content (BWC), and hippocampal levels of oxidative stress markers, inflammatory cytokines, acetylcholine (ACh), and acetylcholinesterase (AChE) were evaluated following the behavioral tests. Histological changes in the hippocampus were examined using hematoxylin and eosin (H&amp;E) staining. Anethole treatment significantly improved scopolamine-induced memory deficits in both NORT and PAT. Furthermore, anethole reduced BBB permeability and BWC in the AD rat model. Hippocampal levels of oxidative stress and inflammation were also attenuated following anethole administration. Additionally, anethole exerted cholinergic effects by inhibiting AChE and increasing ACh levels in the scopolamine-induced AD model. The neuroprotective effects of anethole were further confirmed by H&amp;E staining. Our findings demonstrate that anethole effectively reverses scopolamine-induced memory and cognitive impairments through antioxidant, anti-inflammatory, and anticholinesterase mechanisms in rats. Therefore, anethole may be considered a promising therapeutic candidate for alleviating symptoms of AD and warrants further investigation in future studies.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944391","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":"Adrenergic Modulation of Acetylcholine Release at the Mouse Neuromuscular Junctions of Fast-Twitch Skeletal Muscle","authors":"Arsenii Arkhipov,&nbsp;Nikita Zhilyakov,&nbsp;Guzel Sibgatullina,&nbsp;Egor Nevsky,&nbsp;Ellya A. Bukharaeva,&nbsp;Alexey M. Petrov","doi":"10.1007/s11064-025-04415-w","DOIUrl":"10.1007/s11064-025-04415-w","url":null,"abstract":"<div><p>The sympathoadrenal system functions as an adaptive and trophic system, ensuring increased vitality in humans and animals. Recent findings suggest that, in addition to its effects on muscle tissue, neuromuscular junctions (NMJs) may represent an important target for action of sympathetic mediators. Here, we presented experimental data on neurotransmitter release modulation by adrenergic ligands at the NMJs of mouse fast-twitch skeletal muscle <i>levator auris longus</i>. Adrenaline (but not noradrenaline) increased both spontaneous and evoked acetylcholine (ACh) release. This effect of adrenaline was accompanied by an increase in action potential-elicited Ca²⁺ entry into motor nerve terminals. Blockage of adenylate cyclase and protein kinase A (but not Na, K-ATPase) prevented the facilitatory effect of adrenaline on ACh release. Sympathetic nerves as well as immunoexpression of α1-, α2- and β1-, β2-adrenoceptors (ARs) were revealed in close proximity to the NMJs. Agonists of α2- and β1-ARs had no marked presynaptic effects. α1-AR activation reduced spontaneous and evoked ACh release in a phospholipase A₂ and protein kinase C-dependent manner. Effects of β2-AR activation were dependent on the type of agonist: Procaterol decreased both ACh release and Ca²⁺ entry into the nerve terminals, whereas fenoterol promoted ACh release in a G_i protein-dependent manner. Thus, synaptic transmission in the “fast” NMJs had specific features of adrenergic regulation engaging G_i protein, adenylyl cyclase, phospholipase A₂, protein kinases A and C. The positive effect of natural agonist adrenaline was reproduced only by β2-AR activation with fenoterol, but not α1-, α2-, β1-agonists and β2-agonist procaterol.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938528","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":"Liraglutide Inhibits Autophagy to Ameliorate Post-Cardiac Arrest Brain Injury and Ferroptosis in Rats","authors":"Chengjun Xing,&nbsp;Xin Fan,&nbsp;Mudi Liu,&nbsp;Ye Chen,&nbsp;Jing Jia,&nbsp;Wei Li,&nbsp;Hong Yu,&nbsp;Jun Zhou","doi":"10.1007/s11064-025-04412-z","DOIUrl":"10.1007/s11064-025-04412-z","url":null,"abstract":"<div><p>To investigate whether Liraglutide had a neuroprotective after cardiac arrest and return of spontaneous circulation (CA/ROSC) and explore its potential mechanisms. Adopting an 8-min asphyxial cardiac arrest model. Evaluate the neurological deficit score (NDS), observe pathological changes in hippocampal tissue with HE staining, and measure the expression level of proteins in hippocampal tissue with Western blot. Detection of hippocampal cell apoptosis using TUNEL (TdT-mediated dUTP Nick-End Labeling) method. Immunofluorescence staining was used to detect the expression of LC-3 in the hippocampus, and enzyme linked immunosorbent assay (ELISA) was used to detect the inflammatory factor TNF-α and IL-1β in serum and hippocampus. Autophagy and apoptosis were activated and the expressions of proteins reached significance at 24 h after CA/ROSC. Moreover, rapamycin enhanced apoptosis, ferroptosis and aggravated neuro-pathological damage while 3-methyladenine reduced that. Furthermore, liraglutide treatment improved the 7-day survival rate and NDS, reduced histological signs of injury and inhibited apoptosis, ferroptosis and inflammatory cytokines released after cardiac arrest, and these effects were offset by autophagy agonist. Liraglutide could exert a protective role against post-cardiac arrest brain injury, which could be partially mediated by inhibiting autophagy and ferroptosis. Results clearly indicate that liraglutide may attenuate post-cardiac arrest brain injury (PCABI) by anti-apoptotic and anti-inflammatory via inhibiting autophagy and ferroptosis.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938294","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":"Decoupling of Neurochemical and White Matter Microstructural Integrity in Posterior Cingulate Cortex Predicts Early Alzheimer’s Disease Progression","authors":"Yong-Wen Sun,&nbsp;Xiao-Yang Lei,&nbsp;Xin-Yue Lyu,&nbsp;Yi Yin,&nbsp;Shi-Ji Kan,&nbsp;Zhen-Min Wang,&nbsp;Bo Gao","doi":"10.1007/s11064-025-04405-y","DOIUrl":"10.1007/s11064-025-04405-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by early metabolic and structural brain changes. These alterations are often detectable during mild cognitive impairment due to AD (AD-MCI), a prodromal stage of the disease. The posterior cingulate cortex (PCC), a critical brain region involved in memory and self-referential processing, is particularly vulnerable to these changes. We recruited 21 healthy controls (HC) and 20 AD-MCI patients to participate in this study. Point-Resolved Echo Spin Spectroscopy (PRESS) combined with MEGA-PRESS was employed to accurately measure levels of Gamma-Aminobutyric Acid (GABA) and Glx (Combination of Glutamate and Glutamine) in the PCC. Additionally, diffusion tensor imaging (DTI) was utilized to assess white matter (WM) microstructure integrity. Key metabolites, including N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI), were quantified to provide insights into neuronal health and metabolic status, while WM integrity was evaluated using fractional anisotropy (FA) and mean diffusivity (MD) metrics. In the PCC, AD-MCI patients exhibited a significant reduction in tNAA/tCr (1.22 ± 0.09 vs. HC 1.32 ± 0.07, <i>p</i> &lt; 0.001) and NAA/mI (1.22 ± 0.12 vs. HC 1.44 ± 0.12, <i>p</i> &lt; 0.001), along with an increase in mI/Cr (1.84 ± 0.28 vs. HC 1.60 ± 0.29, <i>p</i> = 0.012) and decreased GABA+/water (2.23 ± 0.78 vs. HC 2.98 ± 0.73, <i>p</i> = 0.003). Diffusion metrics revealed higher mean diffusivity in PCC-connected gray matter (GM_MD: 10.40 ± 0.79 vs. 9.53 ± 0.80 × 10⁻⁴ mm²/s, <i>p</i> &lt; 0.01) and white matter (WM_MD: 0.09 ± 0.01 vs. 0.08 ± 0.01 × 10⁻² mm²/s, <i>p</i> &lt; 0.01). Notably, in AD-MCI, NAA/mI was negatively correlated with WM_MD (<i>r</i> = − 0.462, <i>p</i> = 0.047), and tNAA/tCr was positively correlated with WM_FA (<i>r</i> = 0.580, <i>p</i> = 0.009). PCC neurochemical-microstructural decoupling (NAA/mI-MD dissociation with preserved tNAA/tCr-FA coupling) marks early AD progression. This dissociation pattern, reflecting concurrent neuronal dysfunction and compensatory glial responses, proposes a novel multimodal biomarker for tracking axonal degeneration prior to overt cognitive decline.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925424","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":"Effects and Mechanisms of Paeoniflorin in Relieving Neuropathic Pain: Network Pharmacological Analysis and Experimental Validation","authors":"Fangning Xu,&nbsp;Qingzhen Liu,&nbsp;Shenquan Cai,&nbsp;Qiuyan Yu,&nbsp;Yue Zhang,&nbsp;Zhi Liu,&nbsp;Haishu Zhao,&nbsp;Lidong Zhang","doi":"10.1007/s11064-025-04411-0","DOIUrl":"10.1007/s11064-025-04411-0","url":null,"abstract":"<div><p>Neuropathic pain (NP) is a prevalent condition that can lead to a variety of complications, significantly impacting patients’ quality of life. Previous studies have confirmed that paeoniflorin (PF) demonstrates both therapeutic pain relief and neuroprotective effects. However, its therapeutic efficacy in managing NP remains to be thoroughly investigated. We conducted a systematic study to explore the underlying mechanisms of PF in the treatment of NP through combining network pharmacological analysis with experimental validation. Our studies revealed that PF alleviates NP through a multifaceted approach, mainly involving protein kinase C (PKC), serotonin receptors, calcium signaling pathways, inflammatory mediator regulation of transient receptor potential (TRP) channels, and G-protein coupled receptor signaling pathways. Additionally, our animal experiments indicated that PF reduces pain-related behavior on spinal nerve ligation-induced NP in rats by modulating the PKCε-TRPV1 pathway. PF was found to inhibit the expression of inflammatory factors such as interleukin 6 and tumor necrosis factor α, as well as the activation of microglia, thereby alleviating NP. These findings suggest a potential therapeutic role for PF in the treatment of NP, providing a valuable reference for clinical applications.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04411-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925526","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}