Inflammopharmacology最新文献

{"title":"Correction: The anti‑inflammatory activity of 2‑iminothiazolidines: the role of PPAR-γ and M2 macrophage subpopulations.","authors":"Eduarda Talita Bramorski Mohr, Tainá Larissa Lubschinski, Pedro Augusto Marocco Moro, Larissa Benvenutti, Natáli Tereza Capistrano Costa, Pedro Luís Pereira Braga de Sousa, Marcus Mandolesi Sá, Marcelo Zaldini Hernandes, Flora Aparecida Milton, José Roberto Santin, Eduardo Monguilhott Dalmarco","doi":"10.1007/s10787-026-02422-z","DOIUrl":"https://doi.org/10.1007/s10787-026-02422-z","url":null,"abstract":"","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165659","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 neuroinflammatory-metabolic loop in parkinsonian neurodegeneration.","authors":"Khansa Zahid","doi":"10.1007/s10787-026-02401-4","DOIUrl":"https://doi.org/10.1007/s10787-026-02401-4","url":null,"abstract":"","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165695","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":"Gastroprotective potential of fatty compounds from Persea americana seed: an experimental report.","authors":"Greice Rafaele Alves, Benhur Judah Cury, Bruna Longo, Alexandre Bella-Cruz, Raphael Gilioli Heineck, Rafaela Carvalho Faustino, Yasmim Damian Pompeo Benevides, Luisa Mota da Silva, Rivaldo Niero","doi":"10.1007/s10787-026-02419-8","DOIUrl":"https://doi.org/10.1007/s10787-026-02419-8","url":null,"abstract":"<p><p>Persea americana (Lauraceae) is a fruit widely cultivated in tropical and subtropical regions, commonly known as the avocado. Although the seeds represent a considerable portion of the whole fruit, scientific research on their phytochemistry and biological effects is still in its early stages. This study investigated the gastroprotective effect of the crude methanolic extract (CME-PA; 30-300 mg/kg), the fractions hexane (HF-PA; 100-1000 mg/kg), dichloromethane (DCMF-PA; 30-1000 mg/kg), and ethyl acetate (EAF-PA; 1000 mg/kg) at doses proportional to their yields, as well as isolated compounds (1-4) and a mixture of compounds (M). Gastroprotection was evaluated using the acidified ethanol-induced ulcer model. In addition, the study assessed histological, oxidative, and inflammatory parameters in the gastric mucosa, as well as the in vitro anti-H. pylori activity. Although CME-PA did not prevent the onset of gastric lesions, the HF-PA (300 and 1000 mg/kg), DCMF-PA (1000 mg/kg), and EAF-PA (1000 mg/kg) fractions attenuated acidified ethanol-induced injury by 56.73%, 74.93%, 80.53%, and 52.91%, respectively. Similarly, compounds 4 (300 mg/kg) and M (1, 3, and 10 mg/kg) reduced lesion formation by 52.16%, 56.02%, 66.90%, and 72.89%. Furthermore, compounds 4 (300 mg/kg) and M (3 mg/kg) increased PAS-stained mucin content. Notably, the mixture M, at all tested doses, enhanced the antioxidant defenses of the gastric mucosa and reduced inflammation. Despite these findings, the extract, fractions, and isolated compounds did not exhibit anti-H. pylori activity. Overall, this study provides promising phytochemical and pharmacological evidence, given the significant gastroprotective effects of fractions and isolated compounds against acidified ethanol-induced gastric ulcers. These results highlight the potential of P. americana seeds, often regarded as a by-product of the fruit, as a valuable natural resource for the prevention of gastric ulcer disease.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136483","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":"Essential oil from Piper aduncum L. leaves exhibits analgesic and anti-inflammatory activity in mice.","authors":"Paulo Henrique Eloi Fernandes, Paulo Henrique Andrade do Nascimento Silva, Suyane de Deus E Melo, Bruna de Sousa Gomes, Ryan Cristian da Silva, Laís Ruanita Leopoldina Galvão, Bruno Vinicius Souza da Silva, Maria Clara Morais Cavalcanti, Rayssa Nilma da Silva Alves, Yasmin Antonelle Correia Lira, Júlio César Ribeiro de Oliveira Farias de Aguiar, Daniela Maria do Amaral Ferraz Navarro, Maria Tereza Dos Santos Correia, Wêndeo Kennedy Costa, Márcia Vanusa da Silva","doi":"10.1007/s10787-026-02415-y","DOIUrl":"https://doi.org/10.1007/s10787-026-02415-y","url":null,"abstract":"<p><p>Piper aduncum L. is a medicinal plant whose essential oil is rich in bioactive constituents, particularly dilapiol, and has attracted interest because of its diverse pharmacological properties. However, its anti-inflammatory, antipyretic, and antinociceptive activities and the mechanisms potentially underlying these effects remain insufficiently characterized. Therefore, this study investigated the pharmacological effects of P. aduncum leaf essential oil (EOPa) and explored potential mechanisms involved in its antinociceptive activity. EOPa was obtained by hydrodistillation and chemically characterized by GC-MS and GC-FID. Its pharmacological effects were evaluated in male Swiss mice using brewer's yeast-induced pyrexia, carrageenan-induced paw edema, acetic acid-induced writhing, and the formalin test. Potential mechanisms of antinociceptive activity were investigated using naloxone, atropine, L-NAME, and glibenclamide as pharmacological antagonists/inhibitors. Chemical characterization identified dilapiol as the major constituent of EOPa (69.65 ± 2.12%). EOPa showed dose-dependent anti-inflammatory, antipyretic, and antinociceptive effects, with the most pronounced activity observed at 200 mg/kg. The essential oil reduced inflammatory edema, fever, and nociceptive responses in the experimental models. EOPa at 200 mg/kg reduced yeast-induced fever by up to 76.1% (p < 0.01), carrageenan-induced paw edema by up to 26.48% (p < 0.0001), and acetic acid-induced writhing by 65.90% (p < 0.001). In the formalin test, EOPa reduced nociceptive behavior by 39.89% during the neurogenic phase and by 70.67% during the inflammatory phase (p < 0.0001). Pretreatment with atropine and glibenclamide markedly attenuated the antinociceptive effect of EOPa, whereas naloxone and L-NAME did not significantly modify the response. These findings provide preclinical evidence that P. aduncum leaf essential oil possesses anti-inflammatory, antipyretic, and antinociceptive activities and suggest that the antinociceptive effect of EOPa involves activation of muscarinic receptors, consistent with a muscarinic agonist-like effect, and stimulation of ATP-sensitive potassium (K⁺_ATP) channels, consistent with a K⁺_ATP-channel-stimulating effect. Further pharmacological, toxicological, and mechanistic studies are warranted to clarify the molecular basis, active constituents, and safety profile of these effects.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108880","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":"Enhancing meloxicam efficacy in acute and chronic inflammatory pain: a novel dose-sparing approach using ultramicronized palmitoylethanolamide.","authors":"Samuele Trisolini, Alessandra Toti, Elena Lucarini, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli","doi":"10.1007/s10787-026-02380-6","DOIUrl":"https://doi.org/10.1007/s10787-026-02380-6","url":null,"abstract":"<p><p>Nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, are widely used for the management of inflammatory pain in human and veterinary medicine, although their clinical utility is limited by dose-dependent adverse effects. Strategies aimed at reducing NSAID dosage while preserving analgesic efficacy are therefore warranted. We investigated whether ultramicronized palmitoylethanolamide (PEAum), an endogenous prohomeostatic lipid amide with improved bioavailability, could enhance the antinociceptive effects of meloxicam in preclinical models of acute and chronic inflammatory pain. Acute pain was induced by intraplantar lipopolysaccharide (LPS) injection, while chronic pain was induced by intra-articular injection of Complete Freund's Adjuvant (CFA). Mechanical hyperalgesia and allodynia were measured by the Paw pressure and von Frey tests, respectively. In the LPS model, PEAum confirmed its superior anti-hyperalgesic profile compared with micronized and native PEA. PEAum (10 mg/kg) markedly enhanced the analgesic activity of low-dose meloxicam (3 mg/kg), with the combination fully reversing inflammatory hypersensitivity and outperforming high-dose meloxicam (30 mg/kg). In the CFA model, the same association completely counteracted mechanical hyperalgesia, reproducing the antalgic effect of high-dose meloxicam. A pharmacodynamic study demonstrated that pharmacological blockade of PPAR-α with the selective receptor antagonist GW6471 (2 mg/kg) significantly reduced, but did not abolish, the analgesic effect of the combination, suggesting both PPAR-α-dependent and independent mechanisms. Overall, the combined treatment produced a greater-than-additive antinociceptive effect, demonstrating a synergistic interaction between PEAum and meloxicam in both acute and chronic inflammatory pain. This synergy enables substantial meloxicam dose-reduction while maintaining full analgesic activity, supporting a promising dose-sparing strategy for inflammatory pain management.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108776","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":"Bone and growth safety profiles of biologic and conventional DMARDs in juvenile idiopathic arthritis: a 21-year FAERS disproportionality analysis.","authors":"Fatih Erdem, Nida Gürbüz","doi":"10.1007/s10787-026-02409-w","DOIUrl":"https://doi.org/10.1007/s10787-026-02409-w","url":null,"abstract":"<p><strong>Background: </strong>Juvenile idiopathic arthritis (JIA) treatment relies on biologic and conventional disease-modifying anti-rheumatic drugs (b/csDMARDs), but pediatric-specific bone and growth safety remains incompletely characterized. Standard FAERS disproportionality analyses in pediatric polypharmacy may overstate signals through co-medication coding. We aimed to identify drug-specific bone-toxicity (Composite A) and growth/developmental (Composite B) signals and to test whether they survive a Primary-Suspect (PS) restriction designed to isolate reporter-attributed reactions.</p><p><strong>Methods: </strong>Pre-specified disproportionality analysis of FAERS Individual Case Safety Reports (2004-2024); pediatric (≤ 17 years) JIA cohort, n = 13,459. Two parallel exposure definitions were applied: PS + SS (Primary or Secondary Suspect, broad) and PS-only (strict). Reporting odds ratios (ROR), proportional reporting ratios with χ², IC025 and a fixed-prior Bayesian shrinkage estimate were computed; a robust signal required multi-criteria thresholds in both tracks. The PS + SS analysis was independently reproduced in Python and R, with 100% concordance in signal classification.</p><p><strong>Results: </strong>Of 21 drug × composite signals under broad PS + SS analysis, only 5 met the robust-signal definition after PS-only restriction: methotrexate (both composites; bone ROR 2.4, growth ROR 3.7) and infliximab (4.3), tocilizumab (2.8), and abatacept (3.4) for bone toxicity. Etanercept and adalimumab-the two highest-exposure drugs-showed no PS-only signal despite PS + SS Composite A signals. PS + SS magnitudes attenuated by a median 87% under PS-only restriction.</p><p><strong>Conclusions: </strong>Methotrexate was the only drug with robust bone and growth signals, supporting skeletal and growth surveillance during chronic therapy; three biologics showed bone-toxicity signals. In this cohort, conventional PS + SS analysis substantially overstated signal magnitudes, supporting dual-track (PS + SS and PS-only) reporting for pediatric pharmacovigilance.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109176","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":"Stigmasterol attenuates cuprizone-induced neuroinflammation and demyelination in rats through modulation of inflammatory mediators and oxidative stress.","authors":"Rabeea Safdar, Uzma Saleem","doi":"10.1007/s10787-026-02411-2","DOIUrl":"https://doi.org/10.1007/s10787-026-02411-2","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple sclerosis is a neuroinflammatory and demyelinating condition of brain with limited therapeutic options, many of which are associated with high treatment costs and adverse effects, In this research work, the neuroprotective potential of stigmasterol was investigated in a rat model of cuprizone-induced neuroinflammation and demyelination.</p><p><strong>Materials and methods: </strong>A total of 36 Wistar rats (150-200 g) of both sexes were divided into 6 groups (n = 6) in random manner. Neuroinflammation and demyelination were induced by feeding animals a 0.3% cuprizone-containing diet for 5 weeks. Stigmasterol (100, 200, or 400 mg/kg/day) or dimethyl fumarate (15 mg/kg/day) was then administered orally for 3 weeks while cuprizone administration continued. After behavioral analysis, oxidative stress biomarkers, neurotransmitter levels, myelin-basic protein concentration by ELISA, mRNA expression of myelin basic protein and inflammatory cytokines, and histopathological alternations were evaluated.</p><p><strong>Results: </strong>Cuprizone administration pointedly increased oxidative stress, impaired behavioral performances, induced marked histopathological alterations, reduced mRNA expression of MBP and the anti-inflammatory cytokines, and elevated expression of inflammatory cytokines. Compared with cuprizone group, stigmasterol treatment prominently improved cognitive and locomotor performance (P < 0.001), restored antioxidant status (P < 0.001), upregulated the mRNA expression of IL-4, IL-10 and MBP, downregulated expression of IL-1β, TNF-α and IL-6, and increased both neurotransmitter concentrations (P < 0.001) and MBP concentrations in a dose-dependent manner. The effects of dimethyl fumarate were comparable to those observed with the highest dose of stigmasterol.</p><p><strong>Conclusion: </strong>Stigmasterol alleviated cuprizone-induced neuroinflammation, demyelination, oxidative stress and behavioral deficits while restoring MBP expression and modulating inflammatory cytokines expression. These results suggest that stigmasterol possesses neuroprotective and anti-inflammatory properties and warrants further investigation as an effective therapeutic candidate for demyelinating and neuroinflammatory disorders.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108933","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":"Macrophage polarization plasticity in pulmonary fibrosis: a review from pathogenesis to therapeutic targeting.","authors":"B M Siddesh, Aleena Varughese, Shaharbhanu A Hussain, Nazeerudheen Fathima Beevi, Yashodhar P Bhandary","doi":"10.1007/s10787-026-02414-z","DOIUrl":"https://doi.org/10.1007/s10787-026-02414-z","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by significant extracellular matrix (ECM) accumulation and persistent scarring of lung tissues. Despite improvements in understanding its pathophysiology, effective therapeutic options are limited. Increasing evidence pertains to the critical importance of macrophages, which are major regulators of innate immunity and demonstrate remarkable plasticity that determines PF development. Classically activated M1 macrophages promote pro-inflammatory responses, whereas alternatively activated M2 macrophages facilitate tissue repair and remodelling. In fibrotic lungs, a chronic bias toward M2 phenotypes promotes fibroblast activation, collagen accumulation, and abnormal wound repair. Additionally, macrophage polarization is very dynamic, influenced by cytokines, growth factors, metabolic reprogramming, and epigenetic regulation in the microenvironment. This dynamic flexibility highlights their dual role; protective during acute damage and harmful in chronic fibrosis. Recent research suggests that addressing transcriptional networks and metabolic checkpoints that control macrophage fate can regulate inflammatory and fibrotic responses. Therapeutic approaches targeted at reprogramming macrophages to an M1 phenotype show promise for attenuating or halting fibrotic development. This review underlines the importance of macrophage polarization plasticity in PF, focusing on its dualistic nature and the molecular mechanisms that regulate phenotypic switching. It emphasizes macrophage flexibility as a major area for intervention by combining current insights into macrophage biology with developing treatment approaches, combining innate immune regulation with fibrotic remodelling and highlighting potential strategies to support the restoration of lung homeostasis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108909","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":"Capsicum annuum L. oleoresin attenuates complete Freund's adjuvant-induced arthritis through modulation of COX-2-associated inflammation and oxidative stress.","authors":"Muhammad Adeel Razzaq, Aliza Fatima, Muhammad Shahid, Fozia Anjum, Nayya Waseem Dar, Faiza Umbreen","doi":"10.1007/s10787-026-02416-x","DOIUrl":"https://doi.org/10.1007/s10787-026-02416-x","url":null,"abstract":"<p><p>Rheumatoid arthritis is a chronic autoimmune disorder involving inflammatory cytokine dysregulation, oxidative stress and progressive joint damage. This study evaluated the anti-arthritic activity of Capsicum annuum L. oleoresin using in vitro, in vivo and in silico approaches. Oleoresins were prepared by Soxhlet and maceration extraction with solvents of different polarities and characterized by FTIR and GC-MS. Ethanolic Soxhlet extraction produced the highest yield (29.68%) and strongest antioxidant activity, showing 76.22 ± 0.58% DPPH, 63.77 ± 0.29% H₂O₂, 74.09 ± 0.21% ABTS and 65.49 ± 0.10% FRAP activity. GC-MS tentatively identified 28 compounds, including capsaicinoids, fatty acids, vitamin E and phytosterols. The selected oleoresin showed low hemolytic activity and concentration-dependent protein denaturation inhibition. In complete Freund's adjuvant-induced arthritic rats, oral oleoresin treatment at 100, 200 and 250 mg/kg reduced paw edema and arthritic score, with the 250 mg/kg dose lowering edema to 0.01-0.02 mm by day 28. It also reduced rheumatoid factor from 34.42 to 18.32 IU/L and C-reactive protein from 22.57 to 12.10 mg/dL. TNF-α and IL-6 levels decreased to 25.82 and 8.42 pg/mg protein, respectively, along with marked COX-2 suppression and improved oxidative stress markers. Histopathology examination showed reduced tissue alterations. Docking and molecular dynamics simulation predicted homocapsaicin as a stable COX-2-interacting constituent. These findings suggest that C. annuum oleoresin attenuates experimental arthritis by modulating inflammatory and oxidative stress markers, while further target specific studies are required to confirm the underlying mechanisms.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108489","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":"Stem cells and derived growth factors in Alzheimer's disease: mechanistic insights and translational perspectives.","authors":"Rishika Dhapola, Sneha Kumari, Prajjwal Sharma, Mohit Paidlewar, Balachandar Vellingiri, Ssang-Goo Cho, Ahmed Abdal Dayem, Bikash Medhi, Dibbanti HariKrishnaReddy","doi":"10.1007/s10787-026-02418-9","DOIUrl":"https://doi.org/10.1007/s10787-026-02418-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a significant healthcare concern due to the complex interactions between amyloid-β accumulation, tau pathology, neuroinflammation, synaptic dysfunction, and progressive neuronal death. Stem-cell-based therapies have demonstrated potential to treat this complex condition through immunomodulation, trophic support, and neuroregeneration. Beyond direct cell replacement, stem-cell-derived growth factors have important therapeutic functions by providing strong neurotrophic and cytoprotective effects. These bioactive compounds improve neuronal survival, restore synaptic plasticity, and reduce inflammatory cascades that accelerate the course of AD. Important growth factors that support increased neural resilience, cholinergic preservation, synaptic strengthening, and mitochondrial stabilization include BDNF, NGF, and IGF-1. The current study synthesizes molecular knowledge and new clinical data to assess the translational potential of stem cells and their growth-factor secretome. According to preclinical research, neural stem cells (NSCs) increase synaptic density and maintain cholinergic integrity in APP/PS1 mice, while mesenchymal stem cells (MSCs) lower amyloid burden, inhibit microglial activation, and improve memory. The stem-cell secretome offers a significant therapeutic benefit. BDNF increases synaptic plasticity, NGF promotes cholinergic survival, and IGF-1 improves mitochondrial function and diminishes oxidative stress and tau-mediated toxicity. However, significant obstacles impede clinical advancement. Therapeutic stability is limited by the risks of tumorigenicity, poor long-term engraftment, immunological rejection, and irregular blood-brain barrier penetration. Major challenges persist, such as manufacturing inconsistency, scalability limitations, and difficulties attaining controlled growth-factor dosing. To advance stem-cell-based techniques for significant AD alterations, these hurdles must be overcome by biomaterial optimization, modified secretomes, and standardized production platforms.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109007","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}