Pharmacological research最新文献

{"title":"Phytochemical regulation of CaMKII in Alzheimer’s disease: A review of molecular mechanisms and therapeutic potential","authors":"Zhongying Lin ,&nbsp;Miao Sun","doi":"10.1016/j.phrs.2025.107790","DOIUrl":"10.1016/j.phrs.2025.107790","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a common neurodegenerative disorder that leads to cognitive decline. CaMKII is a calcium-regulated kinase that is crucial for synaptic plasticity and memory. Phytochemicals with diverse origins, safety, and biological activity have attracted considerable attention in AD research. This systematic analysis of phytochemicals targeting CaMKII reveals their neuroprotective mechanisms against AD pathogenesis, highlighting CaMKII as a promising therapeutic target that warrants further preclinical investigation and drug development. We conducted a comprehensive review of the literature of phytochemicals that target CaMKII as a protective mechanism against AD. The search was conducted across multiple databases, including PubMed, Web of Science, China National Knowledge Internet, and Google Scholar, and covered the period from January 2000 to October 2024. A total of 301 articles were retrieved, of which 22 articles were included. The results showed that flavonoid, glycoside, terpene, and polyphenol analogs positively regulated CaMKII expression, whereas alkaloid analogs negatively regulated CaMKII expression. Different components of traditional Chinese medicine played different roles in CaMKII expression. Flavonoid compounds upregulated the expression of SYN, PSD-95, MAP2, and GluR1 to exert neuroprotective effects. Alkaloid and glycoside analogs inhibited Aβ deposition and tau hyperphosphorylation. Terpene analogs upregulated the SYN, PSD-95, NMDAR, BDNF, and PI3K/Akt signaling pathways to exert neuroprotection. Polyphenol analogs upregulated PSD-95, Munc18–1, SNAP25, SYN, and BDNF to exert neuroprotective effects. Emerging evidence demonstrates that select phytochemicals and traditional Chinese medicine compounds exert neuroprotective effects in AD by modulating CaMKII activity, thereby reducing Aβ accumulation, attenuating tau hyperphosphorylation, and enhancing synaptic plasticity, suggesting promising therapeutic potential.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107790"},"PeriodicalIF":9.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124343","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":"Terpenoids: A promising traditional chinese medicine for neuropathic pain relief","authors":"Hui-Si Yang ,&nbsp;David H. Mauki ,&nbsp;Yue-Xiang Zheng ,&nbsp;Ting-Hua Wang ,&nbsp;Xiu-Ying He","doi":"10.1016/j.phrs.2025.107789","DOIUrl":"10.1016/j.phrs.2025.107789","url":null,"abstract":"<div><div>Neuropathic pain (NPP) is a prevalent chronic condition characterized by spontaneous pain, hyperalgesia, allodynia, and sensory abnormalities, severely impacting patients' quality of life. Despite various guided treatments, their clinical efficacy remains limited, often accompanied by adverse reactions. Traditional Chinese medicine (TCM) offers unique advantages in disease treatment through its holistic approach (balancing the body as a unified system) and syndrome differentiation principle (personalized medicine). Recent research has highlighted terpenoids for their analgesic effects and minimal side effects. This review summarizes the role of terpenoids in NPP and their underlying molecular mechanisms. Terpenoids, natural products found in plants, are categorized into monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, and tetraterpenoids based on isoprene units. These compounds alleviate NPP by: inhibiting neuroinflammation and oxidative stress, regulating mitochondrial function, modulating ion channels, and influencing the cannabinoid and opioid receptor systems. This review aims to deepen our understanding of terpenoids and provide crucial evidence and mechanistic insights for their application in NPP therapy.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107789"},"PeriodicalIF":9.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128267","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 regulation of microglia by aging and autophagy in multiple sclerosis","authors":"Xiying Wang,&nbsp;Ye Sun,&nbsp;Haojun Yu,&nbsp;Chunran Xue,&nbsp;Xuzhong Pei,&nbsp;Yi Chen,&nbsp;Yangtai Guan","doi":"10.1016/j.phrs.2025.107786","DOIUrl":"10.1016/j.phrs.2025.107786","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an inflammatory disease that is often characterized by the development of irreversible clinical disability. Age is a strong risk factor that is strongly associated with the clinical course and progression of MS. Several lines of evidence suggest that with aging, microglia have an aging-related gene expression signature and are close to disease-associated microglia (DAM), which exhibit decreased phagocytosis but increased production of inflammatory factors. The gene expression signatures of microglia in MS overlap with those in aging, inflammation and DAM. Moreover, the clearance of damaged myelin by microglia is impaired in the aged brain. Autophagy is a cellular process that decreases in activity with age. In this review, we provide an overview of the role of autophagy and aging in MS. We describe the impact of autophagy and aging on microglial activation in MS and the molecules involved in autophagy and aging, which are related to the phagocytosis and activation of microglia. We propose that a decrease in autophagy in microglia occurs with aging, leading to a decrease in phagocytosis. Decreases in phagocytosis and increases in the production of inflammatory factors by microglia contribute to chronic inflammation in the aged brain and disease progression in MS. Thus, the modulation of autophagy in microglia serves as a potential therapeutic target for MS.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107786"},"PeriodicalIF":9.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120503","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":"Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma","authors":"Larissa Satiko Alcantara Sekimoto Matsuyama ,&nbsp;Victoria Harle ,&nbsp;Victoria Offord ,&nbsp;Alastair Droop ,&nbsp;Roy Rabbie ,&nbsp;Manik Garg ,&nbsp;Martha Estefania Vázquez-Cruz ,&nbsp;Carla Daniela Robles-Espinoza ,&nbsp;Gemma Turner ,&nbsp;David Fraser ,&nbsp;Érica Aparecida de Oliveira ,&nbsp;Danielle Gonçalves de Carvalho ,&nbsp;Natasha Andressa Nogueira Jorge ,&nbsp;Mariana Boroni ,&nbsp;Patricia A. Possik ,&nbsp;David J. Adams ,&nbsp;Silvya Stuchi Maria-Engler","doi":"10.1016/j.phrs.2025.107785","DOIUrl":"10.1016/j.phrs.2025.107785","url":null,"abstract":"<div><div>SIN3 is a critical component of the histone deacetylase complex. Utilizing whole transcriptome data from melanoma patient samples we reveal that elevated levels of <em>SIN3B</em> are associated with poor survival outcomes with <em>in vitro</em> studies showing increased <em>SIN3B</em> expression in <em>BRAF</em>-mutant metastatic melanoma cell lines. The generation of isogenic <em>SIN3B</em> knockout cell lines indicated that <em>SIN3B</em> disruption led to a decrease in pathways associated with tumor invasion, migration, and cell-cell interactions. Moreover, pooled genome-wide CRISPR/Cas9 screens highlighted <em>POLE4</em> and <em>STK11</em> as crucial for the fitness and survival of <em>SIN3B</em>-knockout melanoma cells suggesting a role for these genes in epistasis with <em>SIN3B</em>. In summary, our findings suggest that <em>SIN3B</em> plays a pivotal role in modulating the behavior of melanoma cells, with implications for tumor growth and response to therapy.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"217 ","pages":"Article 107785"},"PeriodicalIF":9.1,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111557","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":"Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms","authors":"Aryan Farahani ,&nbsp;Arman Farahani ,&nbsp;Khosrow Kashfi ,&nbsp;Asghar Ghasemi","doi":"10.1016/j.phrs.2025.107781","DOIUrl":"10.1016/j.phrs.2025.107781","url":null,"abstract":"<div><div>Nitric oxide (NO) is a critical signaling molecule synthesized from <em>L</em>-arginine by nitric oxide synthase (NOS). The three NOS isoforms—neuronal NOS (nNOS; NOS1), inducible NOS (iNOS; NOS2), and endothelial NOS (eNOS; NOS3)—have traditionally been classified as either constitutive (nNOS and eNOS) or inducible (iNOS). However, this binary classification oversimplifies their functions, particularly by neglecting the physiological roles of iNOS and misrepresenting its involvement in pathological processes. Increasing evidence demonstrates that all three isoforms can exhibit both constitutive and inducible expression. Notably, iNOS is constitutively expressed at low levels in several tissues, including blood, heart, bone marrow, lung, brain, spinal cord, retina, colonic mucosa, liver, ileum, skeletal muscle, epidermis, adipose tissue, endometrium, ovary, and kidney under normal physiological conditions, a form we refer to as <em>constitutive iNOS</em> (ciNOS). This basal expression contributes to essential functions such as heart rate regulation, respiratory exchange, and microbiome balance in the gut. Moreover, in certain pathological contexts, iNOS may exert protective rather than harmful effects, challenging the prevailing view that it is solely a pro-inflammatory mediator. Current drug development strategies targeting NOS are largely based on the outdated dichotomy of constitutive “physiologic” versus inducible “pathologic” isoforms, focusing primarily on iNOS inhibition. The failure of iNOS inhibitors in most clinical trials highlights the limitations of this approach. To address these gaps, we propose a revised nomenclature that incorporates both gene expression mode (constitutive vs. inducible) and discovery order, offering a more nuanced framework for understanding NOS isoforms in both health and disease.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107781"},"PeriodicalIF":9.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102103","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 dual role of Mangifera indica L. in regulating immune response and pain persistence in inflammatory bowel disease","authors":"Elena Lucarini ,&nbsp;Anna Schettino ,&nbsp;Noemi Marigliano ,&nbsp;Clara Ciampi ,&nbsp;Martina Smimmo ,&nbsp;Francesca Romano ,&nbsp;Antonio Paolillo ,&nbsp;Luana Izzo ,&nbsp;Jenefa Begum ,&nbsp;Adel Abo Mansour ,&nbsp;Nunzia Iaccarino ,&nbsp;Antonio Randazzo ,&nbsp;Karin Vicente Greco ,&nbsp;Raffaele Scarpa ,&nbsp;Francesco Caso ,&nbsp;Asif Jilani Iqbal ,&nbsp;Mariarosaria Bucci ,&nbsp;Carla Ghelardini ,&nbsp;Lorenzo Di Cesare Mannelli ,&nbsp;Anella Saviano ,&nbsp;Francesco Maione","doi":"10.1016/j.phrs.2025.107773","DOIUrl":"10.1016/j.phrs.2025.107773","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is characterized by chronic intestinal inflammation and immune dysregulation, driven mainly by Th1 and Th17 cells and sustained by pro-inflammatory cyto-chemokines. This inflammatory milieu is associated with visceral pain, a key symptom affecting patient quality of life. Addressing both gut inflammation/immunity and visceral pain is crucial for improving IBD therapy. This study assessed the therapeutic potential of <em>Mangifera indica</em> L. extract (MIE), a mangiferin-rich formulation, in a DNBS-induced colitis model in rats. MIE treatment administered either simultaneously or post-DNBS induction, significantly reduced pathogenic Th1 and Th17 cell infiltration, along with pro-inflammatory cytokines (IL-1β, TNF-α) and chemokines (CXCL1, CXCL2), though histopathology showed no significant improvements in tissue healing. Additionally, MIE restored microbiota–derived short-chain fatty acids (acetate and butyrate) in colon and faecal samples. Importantly, MIE alleviated post-inflammatory visceral hypersensitivity, reducing the abdominal withdrawal reflex (AWR) to colorectal distension (CRD), after either acute or repeated treatment. These findings suggest that MIE, in the context of nutraceuticals and functional foods, shows promise as a dual-action therapeutic strategy for complementary and/or adjuvant therapy in IBD.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"217 ","pages":"Article 107773"},"PeriodicalIF":9.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102150","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":"Berbamine as potential STING inhibitor For KRAS-mutant non-small cell lung cancer","authors":"Haoxin Yan ,&nbsp;Jumin Huang ,&nbsp;Yuwei Wang ,&nbsp;Yizhong Zhang ,&nbsp;Wenkang Ren ,&nbsp;Zhiran Zhai ,&nbsp;Yuping Tang ,&nbsp;Huanling Lai ,&nbsp;Xingxing Fan ,&nbsp;Lihua Liu ,&nbsp;Elaine Lai-Han Leung","doi":"10.1016/j.phrs.2025.107777","DOIUrl":"10.1016/j.phrs.2025.107777","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality. Poor prognostic results in LUAD are frequently associated with KRAS mutations and drug resistance. KRAS mutations can induce STING activation by triggering DNA damage response (DDR) activation. This persistently activated STING signaling gives rise to an immunosuppressive microenvironment, thereby complicating treatment efforts. In this study, we identified that the low-toxicity pro-apoptotic drug Berbamine (BBM) as a potential therapeutic agent for LUAD cells with KRAS mutations. BBM exhibits anti-tumor effects by triggering cell cycle arrest, enhancing senescence, and activating apoptosis. BBM also targets STING, leading to the downregulation of p-STING (Ser366) and CCL2. This in turn reduced the infiltration of M-MDSCs into the tumor microenvironment. These combined mechanisms not only suppress STING-dependent tumor growth but also remodel the immunosuppressive tumor microenvironment, thereby enhancing anti-tumor immunity. Collectively, our findings position BBM as a promising therapeutic agent for LUAD with KRAS mutations, offering a strategy to target STING-associated pathways, overcome immune suppression, and ultimately improve patient outcomes.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107777"},"PeriodicalIF":9.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090091","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":"Therapeutic potential of celastrol in bacterial infections: Current research advancements and future perspectives","authors":"Ziwei Meng ,&nbsp;Qing Liu ,&nbsp;Haowei Chen ,&nbsp;Chun She ,&nbsp;Yongjun Huang","doi":"10.1016/j.phrs.2025.107774","DOIUrl":"10.1016/j.phrs.2025.107774","url":null,"abstract":"<div><div>Drug-resistant bacterial infections and their associated inflammatory diseases constitute a deadly threat to global health. Celastrol is one of the main effective components extracted from the traditional Chinese medicine <em>Tripterygium wilfordii</em> Hook.F (TWHF). An increasing number of researchers have been focusing on the pharmacological properties of celastrol in the context of bacterial infection and associated inflammatory complications. This paper presents a comprehensive review of the pharmacological activity and mechanisms of celastrol in the treatment of bacterial infectious diseases. Celastrol has been demonstrated to possess a range of antibacterial, anti-biofilm, anti-virulence and synergistic antibacterial properties with antibiotics, mediated through diverse molecular mechanisms. Several potential targets of celastrol, such as Δ¹-Pyrroline-5-Carboxylate Dehydrogenase (P5CDH), Filamenting temperature-sensitive mutant Z (FtsZ), and GdpP, have been identified. By acting on these proteins, celastrol can disrupt bacterial structure (e.g., cell walls and membranes), inhibit macromolecular synthesis (protein, RNA, and DNA), and interfere with metabolic pathways. Furthermore, celastrol exerts dual immunomodulatory effects against bacterial infections through the coordinated regulation of host-pathogen interactions: by suppressing critical bacterial virulence factors staphyloxanthin (STX) and chemotaxis inhibitory protein of <em>S. aureus</em> (CHIPS) to counteract immune evasion mechanisms, while simultaneously activating nuclear respiratory factor 1 (Nrf1), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), and various signaling pathways of host immune cells to attenuate infection-induced hyperinflammatory responses and immunocyte-derived tissue damage. Finally, a review and discussion of the therapeutic potential of celastrol is presented, with particular attention to its future development as an effective therapeutic agent for treating diseases associated with bacterial infections.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107774"},"PeriodicalIF":9.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084759","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":"Novel microbially transformed bile acids: Biosynthesis, structure, and function","authors":"Qi Zhao ,&nbsp;Zilei Duan ,&nbsp;Ren Lai ,&nbsp;Pengcheng Ma","doi":"10.1016/j.phrs.2025.107775","DOIUrl":"10.1016/j.phrs.2025.107775","url":null,"abstract":"<div><div>The roles of gut microbiota and microbially modified bile acids in human health have become widely recognized. In the last five years, various microbially modified bile acids (e.g., proteinogenic amino-conjugated bile acids, polyamine-conjugated bile acids, neuroactive amine-conjugated bile acids, methylcysteamine-conjugated bile acids, acylated bile acids, dicarboxylic acid-conjugated bile acids, lithocholic acid (LCA) derivatives) were identified and evaluated, which greatly enriched the mammalian bile acid pool and the bioactivity of bile acids. The structure, enzyme, function, clinical reports of these bile acids, and the bacteria to produce these bile acids were summarized in this review. These novel bile acids had various functions including immunoregulation, receptor regulator, antimicrobial activity, and microbial communities regulating effect. 70, 4, 1, 11, 19, 41, 43, 9, 10 species were observed to produce proteinogenic amino-conjugated bile acids, neuroactive amine-conjugated bile acids, methylcysteamine-conjugated bile acids, acylated bile acids, dicarboxylic acid-conjugated bile acids, 3-oxoLCA, isoLCA, 3-oxoalloLCA, and isoalloLCA, respectively. The current review has shed new light on discovering new bile acid derivatives as drug candidates. These microbially modified bile acids may play important roles in disease such as sleeve gastrectomy, fatty liver, inflammatory bowel disease, cystic fibrosis, and type 2 diabetes, which may also participate in normal physiological processes such as growth of infants, longevity, and dietary habits.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107775"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086418","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":"Paclitaxel-Ang-2-functionalized bionic mesoporous selenium nanoparticles for targeted therapy of glioma","authors":"Huan Shi ,&nbsp;Biaobiao Wang ,&nbsp;Zhiwei Shi ,&nbsp;Huilin Ma ,&nbsp;Yunmei Li ,&nbsp;Ying Liu ,&nbsp;Yu Zhao ,&nbsp;Nan Xia ,&nbsp;Chao Wu ,&nbsp;Yu Gao","doi":"10.1016/j.phrs.2025.107783","DOIUrl":"10.1016/j.phrs.2025.107783","url":null,"abstract":"<div><div>Glioma, the most prevalent primary intracranial tumor, presents significant clinical treatment challenges due to its high invasiveness and therapeutic resistance. Therefore, the development of a targeted therapeutic agent that is both highly effective and low in toxicity is crucial. In this research, we aimed to design a bionic mesoporous selenium nanoparticle (ACMLMSeP) functionalized with paclitaxel and Ang-2 for nasal administration as a targeted treatment approach for glioma. Nasal administration facilitates direct delivery of drugs to the brain through the olfactory nerve, thereby circumventing the protective mechanisms of the blood-brain barrier. Mesoporous selenium (MSe) significantly enhances the loading capacity for insoluble drugs while improving their water solubility. The functionalization of MSe enables slow drug release and facilitates targeted drug accumulation. Moreover, accumulated nano-selenium promotes reactive oxygen species (ROS) production, induces autophagy, and synergizes with drugs to accelerate apoptosis in tumor cells. Analysis using Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) indicated that ACMLMSe has an average particle size of roughly 135 nm. Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34 % within 24 h. Cellular uptake studies and in vivo imaging showed the strong targeting capabilities of the ACMLMSeP nanoparticles. Furthermore, the results obtained from the MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations collectively revealed that ACMLMSeP effectively inhibited proliferation while promoting apoptosis in C6 cells. In summary, these experimental findings clearly suggest that ACMLMSeP may serve as a promising biomimetic nanosystem for the targeted treatment of brain glioma.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107783"},"PeriodicalIF":9.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071110","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}