Saad Misfer Alqahtani, Basel A Abdel-Wahab, Ehab A M El-Shoura, Magy R Kozman, Lobna A Abdelzaher, Nesreen I Mahmoud, Hend Mostafa Selim, Mohamed A Gad, Sherif A Mohamed, Eman K Rashwan, Hebatallah M Saad, Ahmed Gaafar, Ayah M H Gowifel
{"title":"Neuroprotective effects of dapansutrile in rotenone-induced parkinsonism: targeting NLRP3/caspase-1, NF-κB, Nrf2/HO-1, and PINK1/Parkin pathways.","authors":"Saad Misfer Alqahtani, Basel A Abdel-Wahab, Ehab A M El-Shoura, Magy R Kozman, Lobna A Abdelzaher, Nesreen I Mahmoud, Hend Mostafa Selim, Mohamed A Gad, Sherif A Mohamed, Eman K Rashwan, Hebatallah M Saad, Ahmed Gaafar, Ayah M H Gowifel","doi":"10.1007/s10787-026-02387-z","DOIUrl":"https://doi.org/10.1007/s10787-026-02387-z","url":null,"abstract":"<p><strong>Background and purpose: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic dysfunction, neuroinflammation, oxidative stress, and mitochondrial abnormalities. Activation of the NLRP3 inflammasome has been implicated in PD pathophysiology; however, its relationship with other pathological processes remains incompletely understood. The present study investigated the neuroprotective effects of dapansutrile (DPST), a selective NLRP3 inhibitor, in a rotenone (ROTN)-induced rat model of parkinsonism and examined its effects on inflammation-, oxidative stress-, mitophagy-, and apoptosis-related markers.</p><p><strong>Methods: </strong>Forty-four adult male Wistar rats were randomly allocated into four groups: control, DPST-treated control (200 mg/kg/day, p.o.), ROTN-treated (1.5 mg/kg, s.c., every other day for 21 days), and ROTN + DPST-treated groups. Behavioral assessments were conducted followed by biochemical, molecular, histopathological, and immunohistochemical analyses of brain tissues. Markers related to oxidative stress, inflammatory signaling, mitophagy-associated pathways, and apoptosis-associated signaling were evaluated.</p><p><strong>Results: </strong>ROTN administration induced marked behavioral deficits, dopamine depletion, oxidative stress, neuroinflammation, histopathological alterations, and increased GFAP immunoreactivity. These changes were accompanied by increased NLRP3 expression, caspase-1 activity, IL-18 levels, and Apaf-1 expression, together with reduced PINK1, Parkin, and MFN1 protein expression. DPST treatment significantly improved behavioral performance, restored dopamine and BDNF levels, attenuated oxidative stress and inflammatory responses, reduced NLRP3-associated inflammatory markers, improved the expression of PINK1-, Parkin-, and MFN1-related proteins, and lowered Apaf-1 expression. Furthermore, DPST ameliorated the histopathological alterations and astroglial activation induced by ROTN.</p><p><strong>Conclusion: </strong>DPST exerted significant neuroprotective effects in the rotenone-induced rat model of parkinsonism. These beneficial effects were associated with modulation of NLRP3-associated inflammatory signaling, attenuation of oxidative stress, and alterations in mitophagy-related and apoptosis-related markers. While the findings support a potential role for NLRP3 signaling in ROTN-induced neurotoxicity, the present data establish associations rather than direct causal mechanisms. Further studies employing dedicated assessments of pyroptosis, mitophagic flux, mitochondrial function, apoptosis, and dopaminergic neuronal survival are required to clarify the mechanistic basis of DPST-mediated neuroprotection.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109001","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}
Diptirani Rath, Subhasish Sahoo, Om Archita Panda, Sandesh Kumar Pattanaik, Swarna Prava Lenka
{"title":"Elucidating the anti-arthritic potential of Crinum asiaticum L. through the TNF signalling pathway: an integrated computational pharmacology, in-vitro and in-vivo approach.","authors":"Diptirani Rath, Subhasish Sahoo, Om Archita Panda, Sandesh Kumar Pattanaik, Swarna Prava Lenka","doi":"10.1007/s10787-026-02404-1","DOIUrl":"https://doi.org/10.1007/s10787-026-02404-1","url":null,"abstract":"<p><p>Crinum asiaticum L. has been traditionally used for a long time to treat pain, inflammation, rheumatoid arthritis and other inflammatory disorders. However, the anti-arthritic activity and molecular mechanisms of these effects are not well characterised despite its extensive ethnomedicinal use. The present study investigated the anti-arthritic potential of the methanol extract of C. asiaticum (MECA) using an integrated in-silico, in-vitro and in-vivo approach. The phytochemical profile of MECA was characterized by HRLC-QToF-MS analysis, which tentatively identified 23 phytoconstituents. Network pharmacology identified 69 overlapping targets between MECA associated proteins and rheumatoid arthritis-related genes, while GO and KEGG enrichment analyses highlighted several inflammation related pathways among which the TNF signalling pathway emerged as a prominent enriched pathway associated with the anti-arthritic effects of MECA. Molecular docking supported interactions between selected phytoconstituents and inflammatory targets, while molecular dynamics simulation further supported the stability of the Narciclasine-COX-2 complex. In IL-1β-stimulated SW982 human synovial cells, MECA significantly reduced the production of TNF-α, IL-1β, IL-6, PGE₂, nitric oxide and downregulated the expression of AKT1, COX-2 and IL-6. In the Complete Freund's Adjuvant induced arthritis rat model MECA attenuated paw inflammation and arthritic severity, improved biochemical and inflammatory parameters and protected joint architecture, as confirmed by radiographic and histopathological analyses. Collectively, these findings support the anti-arthritic activity of MECA and indicate that TNF-associated signalling may contribute to its observed anti-inflammatory effects. This study provides scientific evidence supporting the traditional use of C. asiaticum and highlights its potential as a complementary therapeutic candidate for the management of rheumatoid arthritis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069345","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":"NLRP3 Inflammasome Inhibitors as Precision Anti-inflammatory Pharmacotherapy: Translational Advances, Clinical Evidence, and Disease-specific Challenges.","authors":"Md Farhan Raza, Alok Kumar, Hibah, Laiba Rizvi, Farheen Aftab, Mansi Devi, Sanchi Gupta, Sourabh Kosey","doi":"10.1007/s10787-026-02408-x","DOIUrl":"https://doi.org/10.1007/s10787-026-02408-x","url":null,"abstract":"<p><p>The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is pivotal ininnate immunity and inflammatory disease pathogenesis, notably through interleukins (IL)-1β and IL-18 and by triggering gasdermin D (GSDMD)-mediated pyroptosis. It has been implicated in cardiometabolic, renal, neuroinflammatory, and immune-mediated diseases, making NLRP3 a potential target for selective anti-inflammatory therapy. Clinical efficacy may vary according to disease biology, degree of NLRP3 inhibition, tissue distribution, and patient selection. This review covers the pharmacological and translational research of development of NLRP3 inhibitors and it summarizes the emerging clinical evidences from databases like PubMed, Scopus, Web of Science, Embase and ClinicalTrials.gov. It discusses several direct small-molecule NLRP3 inhibitors, including dapansutrile and selnoflastand others, including upstream activation mechanisms and downstream inflammatory mediators. Pharmacologic selectivity, potency, tissue distribution, activation of NLRP3 and clinical efficacy are among the key factors to consider in anti-inflammatory drug development. The success of these drugs in current use is variable, depending on the inflammatory type of the disease and the first generation of these drugs has shown liver toxicity. The role of the inflammasome in these conditions further supports the need for targeting NLRP3, especially in diseases such as cardiometabolic, renal and neuroinflammatory, but there are still hurdles to overcome, such as patient stratification and validation of biomarkers. Biomarker enriched populations should be targeted as a next step to improve the effectiveness of selective NLRP3 inhibition over current therapies.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069386","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":"Untargeted LC-QTOF-MS/MS metabolomics and integrative pharmacology identify candidate triterpenoids associated with the gastrointestinal activity of Baliospermum montanum root extract.","authors":"Kirtan Dave, Prasenjit More, Suwarna Meshram","doi":"10.1007/s10787-026-02402-3","DOIUrl":"https://doi.org/10.1007/s10787-026-02402-3","url":null,"abstract":"<p><p>Baliospermum montanum (Willd.) has been investigated for its gastrointestinal effects, but its metabolite composition and potential mechanisms underlying these effects remain insufficiently characterized. This study employed an integrative framework combining untargeted metabolomics, computational pharmacology, and in vivo evaluation to characterize candidate constituents and potential mechanisms associated with the gastrointestinal effects of B. montanum root extract. Methanolic root extract was profiled using untargeted LC-QTOF-MS/MS in positive and negative electrospray ionization modes. Facility-assisted database/library annotation and manual curation identified 15 prioritized putative metabolite annotations, including the triterpenoid candidates cucurbitacin C, ganoderic acid F, ursolic acid, and 24-hydroxyglycyrrhetic acid. In accordance with the Metabolomics Standards Initiative framework, these compounds were classified as Level 2 putative annotations because authentic reference standards were not analyzed under identical experimental conditions. Network pharmacology, molecular docking, and molecular dynamics simulations were performed against gastrointestinal regulatory targets, including dopamine receptor D2 (DRD2), 5-hydroxytryptamine receptor 1A (5-HT1A), and cystic fibrosis transmembrane conductance regulator (CFTR). Cucurbitacin C showed a comparatively favorable predicted interaction profile among the prioritized candidates, while the corresponding DRD2-associated complex maintained a root-mean-square deviation below 2 Å during molecular dynamics simulation, supporting stability of the simulated complex. In vivo, oral administration of the root extract to Wistar rats for five consecutive days at 300-900 mg/kg produced significant dose-related changes in fecal characteristics, stool output, and defecation frequency, with the greatest responses observed at 900 mg/kg (p < 0.001). No significant changes in body weight or serum AST, ALT, and ALP were observed under the tested conditions, providing no biochemical evidence of hepatocellular injury. Histopathological examination of the colon demonstrated alterations in goblet-cell mucin, crypt morphology, epithelial appearance, edema, and inflammatory features, consistent with changes in colonic secretory activity and mucosal architecture. Collectively, these findings indicate that B. montanum root extract produces measurable gastrointestinal effects accompanied by alterations in intestinal secretory and mucosal parameters. Integrative computational analysis identified potential interactions of prioritized putative metabolites with gastrointestinal regulatory targets, with cucurbitacin C emerging as a candidate constituent for further investigation. These findings provide a basis for future experimental validation of the metabolite-target relationships underlying the gastrointestinal activity of B. montanum root extract.Keywords: Baliospermum montanum; Untargeted LC-MS/MS metabolomic","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060418","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}
Sunil Shukla, Chanchal Tiwari, Sunil Sharma, Neeru Vasudeva, Ramchander Khatri, Mohammad Ovais Dar, Tanuj Hooda, Amit Lather
{"title":"Neuroprotective potential of Prunetin in streptozotocin-induced cognitive dysfunction: insights from computational and experimental studies.","authors":"Sunil Shukla, Chanchal Tiwari, Sunil Sharma, Neeru Vasudeva, Ramchander Khatri, Mohammad Ovais Dar, Tanuj Hooda, Amit Lather","doi":"10.1007/s10787-026-02403-2","DOIUrl":"https://doi.org/10.1007/s10787-026-02403-2","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) accounts for over 85% of global diabetes cases and is strongly associated with cognitive decline resulting from chronic hyperglycemia-induced neuronal and oxidative damage. Prunetin, a natural isoflavone known for potent antioxidant and antidiabetic activity, was investigated for its potential to attenuate diabetes-associated cognitive deficits.</p><p><strong>Methods: </strong>In silico analysis included molecular docking, MM-GBSA binding free energy, and molecular dynamics simulations (100 ns) to explore interactions between Prunetin and human acetylcholinesterase (AChE; PDB ID: 7D9O). In vivo studies were conducted in streptozotocin (STZ)-induced diabetic rats, with cognition assessed using the Morris water maze. Brain tissues were examined for Aβ(1-42), lipid peroxidation, reduced glutathione (GSH), and AChE activity to determine oxidative status and cholinergic function.</p><p><strong>Results: </strong>Prunetin (0.5 mg/kg/day) administered for 14 (acute) or 28 days (chronic) reduced blood glucose levels, Aβ(1-42) accumulation, and lipid peroxidation while increasing GSH levels and inhibiting AChE activity in a duration-dependent manner. These effects corresponded with significant improvements in Morris water maze performance, with 28-day treatment demonstrating greater efficacy than the 14-day regimen for most parameters. Computational modeling confirmed stable Prunetin-AChE complex formation mediated by hydrogen bonding, hydrophobic interactions, and π-π stacking interactions.</p><p><strong>Conclusion: </strong>Prunetin demonstrates notable antioxidant and AChE-inhibitory properties, attenuating STZ-induced cognitive dysfunction in an experimental rat model. These findings collectively support Prunetin as a promising multitarget candidate warranting further investigation for diabetes-associated neurodegeneration.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060354","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":"Development and optimization of 6-Hydroxyflavone-loaded nanoemulgel for enhanced topical anti-inflammatory activity.","authors":"Pratiksha Prabhakar Sangale, Mahesh Hari Kolhe, Rajashree Dadasaheb Ghogare, Gaurao Subhash Damre","doi":"10.1007/s10787-026-02410-3","DOIUrl":"https://doi.org/10.1007/s10787-026-02410-3","url":null,"abstract":"<p><strong>Objectives: </strong>To develop and optimize a 6-Hydroxyflavone (6-HF)-loaded nanoemulgel using a Box-Behnken Design (BBD)-based Quality by Design (QbD) approach for enhanced topical anti-inflammatory activity, addressing the limitations of poor aqueous solubility and inadequate transcutaneous bioavailability of 6-HF.</p><p><strong>Methods: </strong>Drug-excipient compatibility was confirmed via the use of preformulation studies such as DSC and FTIR. Pseudo-ternary phase diagrams were built to determine the region of existence of the nanoemulsion. A three-factor, three-level BBD was used to maximize the oleic acid (X1), Tween 80 (X2) and Transcutol P (X3) concentrations, and particle size and PDI were the responses. The optimized nanoemulsion was added to the Carbopol 934 gel bases in four concentrations (0.5-2.0% w/v) to form nanoemulgel batches (NEG1-NEG4), evaluated for physicochemical characteristics, ex vivo skin permeation, and in vivo anti-inflammatory activity using a carrageenan-induced paw oedema model, and in vivo in anti-inflammatory activity using carrageenan induced paw edema model.</p><p><strong>Results: </strong>The quadratic models demonstrated excellent predictability (adjusted R<sup>2</sup> = 0.9851 and 0.9660 for particle size and PDI respectively). The optimized nanoemulsion NF16 exhibited particle size 136.4 nm, PDI 0.211, zeta potential - 26.5 mV, and entrapment efficiency 87.9%. NEG2 (1.0% Carbopol 934) was selected as the optimized nanoemulgel based on superior ex vivo drug release (94.2% at 12 h), balanced viscosity (4256 cP), and spreadability (22.6 g.cm/sec). In vivo studies demonstrated 58.41% paw edema inhibition, statistically comparable to but not superior to standard Diclofenac gel 1% (62.15%) in a carrageenan-induced acute inflammation model Diclofenac gel 1% (62.15%).</p><p><strong>Conclusion: </strong>The developed 6-HF nanoemulgel demonstrated promising preclinical topical anti-inflammatory efficacy with favourable physicochemical stability. While 6-Hydroxyflavone is a naturally occurring flavonoid with a reported safety profile in preclinical models, direct claims of safety superiority over conventional NSAIDs cannot be made without skin irritation testing, repeated-dose toxicity studies, systemic exposure assessment, and clinical investigation, which warrant further evaluation.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060347","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":"Rewiring the psoriasis-metabolism axis: therapeutic potential of saroglitazar beyond PPAR modulation.","authors":"Kanika Vashisht, Himanshu Kumar, Swati Rana, Mahendra Singh Ashawat, Shiv Kumar Kushawaha","doi":"10.1007/s10787-026-02413-0","DOIUrl":"https://doi.org/10.1007/s10787-026-02413-0","url":null,"abstract":"<p><p>Psoriasis (PSO) is a chronic, immune-mediated inflammatory disorder that affects approximately 2-3% of the global population, or over 100 million individuals worldwide. Far beyond its cutaneous manifestations, PSO is now recognized as a systemic inflammatory condition tightly intertwined with metabolic syndrome, insulin resistance, and heightened cardiovascular risk. Clinical and epidemiological data reveal its strong association with type 2 diabetes, hypertension, dyslipidemia, hepatic steatosis, and non-alcoholic fatty liver disease, collectively amplifying its systemic burden. At the molecular level, these comorbidities converge on dysregulated signaling cascades, including NF-κB, MAPK, and STAT3, that sustain the chronic pro-inflammatory state. Saroglitazar (SGZ), initially developed as a dual PPAR-α/γ agonist for diabetic dyslipidemia, is indeed emerging as a promising multi-targeted therapy with pleiotropic effects. Current evidence supports its role as a system-level modulator that fine-tunes insulin signaling, reduces oxidative stress, suppresses neuroinflammation, and modulates key inflammatory pathways such as NF-κB, MAPK, and STAT3, aligning well with its broadened therapeutic potential beyond diabetes management. To our knowledge, this is the first comprehensive synthesis to unravel SGZ's mechanistic intersections across metabolic and inflammatory axes and map its clinical relevance to psoriasis. By bridging the dermatological landscape with metabolic comorbidity management and lifestyle interventions, SGZ-proposed mechanisms in the skin, however, have not yet been thoroughly investigated with direct preclinical and clinical evidence in psoriasis and are still hypothesis-generating.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060420","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}
Arslan Rasool, Muhammad Shahid, Zahid Mushtaq, Bushra Akhtar
{"title":"Molecular docking-guided identification of multi-target anti-inflammatory phytochemicals from almond (Prunus dulcis) gum and experimental validation of almond gum-mediated silver/zinc oxide nanobiocomposites for accelerated wound healing.","authors":"Arslan Rasool, Muhammad Shahid, Zahid Mushtaq, Bushra Akhtar","doi":"10.1007/s10787-026-02391-3","DOIUrl":"https://doi.org/10.1007/s10787-026-02391-3","url":null,"abstract":"<p><p>Wound healing is a complex biological process where uncontrolled inflammation often delays tissue repair, imposing a significant clinical and economic burden worldwide. This study aimed to develop and evaluate almond gum (Prunus dulcis) based silver and zinc oxide nanobiocomposites (AG-Ag and AG-ZnO) through integrated computational, In-vitro and In-vivo studies as a promising therapeutic approach for accelerating wound healing. This study is the first to comparatively evaluate Ag-NPs and ZnO-NPs within the same almond gum matrix. A total of 31 phytoconstituents of Prunus dulcis were screened for ADME properties via pkCSM, and potential bioactive compounds were docked against COX-2, TNF-α, and VEGFR-2. Quercetin-3-diglucoside and Corosolic acid recorded the strongest binding affinities toward COX-2 (- 8.8 kcal/mol), mechanistically supporting the anti-inflammatory basis of Prunus dulcis. The green-synthesized nanobiocomposites were characterized via UV-Vis spectroscopy, FTIR, XRD, SEM, zeta sizer, and zeta potential, with mean particle sizes of 73.33 nm and 225.2 nm for AG-Ag and AG-ZnO, respectively. In-vitro studies revealed strong antioxidant activity, with AG-ZnO exhibiting the highest TPC (342.29 ± 1.18 µg GAE/g) and TFC (158.20 ± 0.40 µg CE/g), and AG-P the lowest DPPH IC50 (47.67 ± 2.01 µg/mL). Both nanobiocomposites further demonstrated potent antibacterial and anti-biofilm activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis, alongside significant anti-inflammatory activity and negligible hemolytic toxicity. In vivo evaluation using a rabbit excisional wound model demonstrated superior wound contraction with AG-Ag (90%) and AG-ZnO (93%) compared to the standard drug Polyfax (68%) and untreated control groups. Treatment groups also showed significant modulation of inflammatory biomarkers (ESR, CRP, IL-6) at Days 7 and 15 compared to controls. Histopathological studies showed active collagen deposition, fibroblast migration, and keratinocyte proliferation. These findings collectively concluded Prunus dulcis gum-stabilized Ag/ZnO nanobiocomposites as safe, mechanistically validated, and biocompatible candidates for advanced wound healing therapeutics.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060276","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}
Leena Das, Manas Das, Luit M Barkalita, Probodh Borah, Ananya Chetia, Momita Rani Baro, Ratul Chakraborty, Aashis Dutta
{"title":"Myrica esculenta fruit extract as a nutraceutical supplement mitigating LPS-induced inflammation through COX-2 and iNOS modulation: integrated in vitro, in vivo, and docking approaches.","authors":"Leena Das, Manas Das, Luit M Barkalita, Probodh Borah, Ananya Chetia, Momita Rani Baro, Ratul Chakraborty, Aashis Dutta","doi":"10.1007/s10787-026-02407-y","DOIUrl":"https://doi.org/10.1007/s10787-026-02407-y","url":null,"abstract":"<p><p>Myrica esculenta Buch. -Ham. ex D. Don, traditionally referred to as \"Noga Tenga\" in Assam and \"Soh-Phi\" by the Khasi tribe, holds a longstanding place in Indian medicine for antimicrobial, antidiabetic, and respiratory ailments. This study evaluates the anti-inflammatory potential of the methanolic extract of M. esculenta fruit (MEMEF) in LPS-challenged RAW 264.7 macrophages and a complementary in vivo system. Swiss albino male mice (n = 6) were pre-treated orally with MEMEF for seven days followed by a single intraperitoneal dose of LPS (3 mg/kg bw). Serum AST, ALT, ALP, NO, PGE2, and cytokines were measured, and inos and cox-2 mRNA expression was analyzed by qPCR. In vitro, RAW 264.7 cells were pre-treated with MEMEF (16.7 and 33.5 µg/ml) and stimulated with LPS (1 µg/ml) for 24 h. LC-MS analysis identified major phytoconstituents, and molecular docking examined interactions of epigallocatechin-3-gallate, resveratrol, and myricitrin with COX-2 and iNOS. MEMEF pre-treatment significantly reduced LPS-induced elevations of serum biochemical markers and inflammatory mediators, with qPCR confirming downregulation of inos and cox-2 in treated groups. In vitro, MEMEF markedly decreased NO and PGE2 production and suppressed inos and cox-2 expression in activated RAW 264.7 cells. Docking results showed strong binding of epigallocatechin-3-gallate to both target proteins, suggesting a possible contribution of these interactions to the observed anti-inflammatory effects. Overall, MEMEF exhibited anti-inflammatory activity in cellular and animal models, supporting its promise as a therapeutic candidate for inflammation-related disorders and highlighting its value as a source of nutraceutical supplement derived from a traditionally consumed functional fruit.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060299","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}
Naheed Akhter, Nazma Nasir, Muhammad Irfan, Zunera Chauhdary
{"title":"Aegle marmelos neuroprotective potential in demyelination rat model through modulation of BDNF, GDNF, HSP-90 and HSP-60.","authors":"Naheed Akhter, Nazma Nasir, Muhammad Irfan, Zunera Chauhdary","doi":"10.1007/s10787-026-02376-2","DOIUrl":"https://doi.org/10.1007/s10787-026-02376-2","url":null,"abstract":"<p><p>Multiple sclerosis is a neurodegenerative disorder marked by axonal damage and demyelination; however, existing immunomodulatory treatments are ineffective requiring development of new therapeutic approaches. Aegle marmelos, a traditional medicinal plant rich in bioactive phytochemicals. This study examined the neuroprotective effects of Aegle marmelos ethanolic fruit extract (AME) in a cuprizone (CPZ)-induced MS rat model. AME GC-MS analysis and molecular docking analysis were performed. Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg). Following 42 days of treatment neurobehavioural observation, biochemical analysis, neurotransmitters, gene expression for inflammatory cytokines, and histopathological examination were conducted. GC-MS analysis identifies neuroactive substances, including as fatty acids, phytosterols, and phenolic derivatives. Administration of AME reduced CPZ-induced behavioural deficits in a dose-dependent manner; the 750 mg/kg dose showed significant improvements in motor coordination, grip strength, spatial working memory (p < 0.001). Pro-inflammatory mediators were markedly downregulated by RT-PCR, while antioxidant enzyme activities and neurotransmitters concentrations were also restored. AME treatment dose dependently restored serum level of BDNF, GDNF and decreased expression of HSP-90 and 60. AME treatment decreased the elevated expression of inflammatory cytokines, leukotrienes, prostaglandins and oxidative stress markers showing more pronounced antioxidant and anti-inflammatory potential. According to histopathological examination, AME-treated groups showed less demyelination and plaque formation with preserved neuronal architecture. By concurrently reducing oxidative stress, neuroinflammation, and promoting remyelination, these results show that AME exhibits strong neuroprotection. Multiple sclerosis is a neurodegenerative disorder marked by axonal damage and demyelination; however, existing immunomodulatory treatments are ineffective requiring development of new therapeutic approaches. Aegle marmelos, a traditional medicinal plant rich in bioactive phytochemicals. This study examined the neuroprotective effects of Aegle marmelos ethanolic fruit extract (AME) in a cuprizone (CPZ)-induced MS rat model. AME GC-MS analysis and molecular docking analysis were performed. Sixty Wistar rats were divided into six groups: Control, MS model group (CPZ 0.2% in chow diet for 42 days), standard (fingolimod 15 mg/kg), and AME treatment groups (250, 500, and 750 mg/kg). Following 42 days of treatment neurobehavioural observation, biochemical analysis, neurotransmitters, gene expression for inflammatory cytokines, and histopathological examination were conducted. GC-MS analysis identifies neuroactive substances, including as fatty acids, phytosterols, and phenolic derivatives. Administra","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873693","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}