Inflammopharmacology最新文献

{"title":"Effects of resveratrol supplementation on inflammatory and oxidative stress biomarkers in metabolic disorders: a systematic review and dose-response meta‑analysis of randomized controlled trials.","authors":"Soheil Rahmati, Danyal Imani, Zeinab Alizadeh, Ladan Hassani, Navid Dashti, Azadeh Nikseresht, Saeed Aslani","doi":"10.1007/s10787-026-02424-x","DOIUrl":"https://doi.org/10.1007/s10787-026-02424-x","url":null,"abstract":"<p><strong>Background: </strong>Chronic low-grade inflammation and oxidative stress are hallmarks of metabolic disorders. A naturally occurring polyphenol, resveratrol (RSV), has shown promise in modulating these pathways, however clinical evidence is mixed. To systematically review and perform a dose-response meta-analysis of randomized controlled trials (RCTs) to assess the effects of RSV supplementation on inflammatory and oxidative stress biomarkers in patients with these disorders.</p><p><strong>Methods: </strong>A systematic search up to August 2026 following PRISMA guidelines was conducted to identify RCTs that examined the effect of RSV on inflammatory (including C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)) and oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC)) biomarkers in populations with metabolic disorders. Random effects models were used to combine the data. Dose-response relationships were evaluated using linear and non-linear modelling. Trial sequential analysis (TSA) was performed to adjust for repetitive testing, calculate the required information size (RIS), and assess the robustness of the cumulative evidence.</p><p><strong>Results: </strong>Meta-analysis of 25 RCTs for CRP showed a statistically significant reduction (SMD = -0.18, 95% CI: -0.33 to -0.03, p = 0.0202, I² = 20%), while IL-6 and TNF-α showed non-significant changes with high heterogeneity. Regarding oxidative stress markers, no significant overall effects were observed for CAT, MDA, or SOD. Analysis of TAC showed a non-significant trend (SMD = 0.63, 95% CI: -0.08 to 1.33, p = 0.0668, I² = 58.5%), which became statistically significant only after the exclusion of one influential outlier trial (SMD = 0.83, 95% CI: 0.23 to 1.44, p = 0.0273, I² = 0%). TSA crossed the monitoring boundary for CRP, supporting an anti-inflammatory effect, while evidence for other biomarkers remained inconclusive. Dose-response meta-analyses identified no significant linear or non-linear associations between daily RSV dosage and inflammatory outcomes.</p><p><strong>Conclusion: </strong>RSV supplementation is associated with a modest reduction in CRP, supported by TSA; however, effects on other inflammatory and oxidative stress biomarkers were null or inconclusive. The absence of a clear dose-response relationship and the surrogate status of CRP limit the clinical interpretability of these findings.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216068","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":"Leukotriene inhibitors in multiple sclerosis: a systematic review of animal studies.","authors":"Sina Pakkhesal, Shideh Roshani, Ali Mehdizadeh Kahnamoyi, Mahsa Aminzadeh, Sina Ghasemi, Farinaz Amirikar, Mahnaz Talebi, Sarvin Sanaie, Amirreza Naseri","doi":"10.1007/s10787-026-02429-6","DOIUrl":"https://doi.org/10.1007/s10787-026-02429-6","url":null,"abstract":"<p><p>Current disease-modifying therapies for multiple sclerosis (MS) primarily target adaptive immunity but often fail to halt neurodegeneration or promote myelin repair. Leukotriene pathway inhibitors, established in the management of asthma, possess anti-inflammatory and potentially neuroprotective properties. Following the PRISMA 2020 recommendations, a systematic search was conducted in PubMed, Web of Science, and Scopus. Eligible studies included preclinical investigations of leukotriene inhibitors in MS animal models and risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. Five studies met the inclusion criteria, reported that inhibition of leukotriene B4 (LTB4) or cysteinyl leukotriene receptor 1 (CysLT1) attenuated clinical severity in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination models. Mechanistically, the included preclinical studies suggest that leukotriene inhibitors may influence several pathways potentially relevant to MS pathophysiology, including T helper 17 (Th17) cell differentiation, M1-like microglial polarization, and oligodendrocyte precursor cell (OPC) differentiation. In addition, targeted central nervous system (CNS) delivery using engineered exosomes appeared to enhance the observed remyelination effects. Leukotriene inhibition may exert pleiotropic effects across both peripheral immune responses and the CNS microenvironment. Although these mechanistic observations provide biological plausibility for further investigation of these agents as potential repurposed therapies for MS, particularly in the context of remyelination and neuroinflammation, they remain based on preclinical evidence and should therefore be considered hypothesis-generating. Well-designed clinical studies are required to determine whether these experimental effects translate into clinically meaningful therapeutic benefits in patients with MS.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193269","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 dual role of capsaicin in inflammatory bowel disease: from TRPV1-mediated protection to neurogenic inflammation.","authors":"Luyun Zhang","doi":"10.1007/s10787-026-02426-9","DOIUrl":"https://doi.org/10.1007/s10787-026-02426-9","url":null,"abstract":"<p><p>Capsaicin, the pungent vanilloid of chili pepper, is a widely consumed dietary constituent that exerts pleiotropic actions on physiological and pathophysiological processes, including anti-inflammatory, antioxidant, antiproliferative, metabolic and cardioprotective effects. Capsaicin is a small, highly lipophilic molecule that is not appreciably hydrolyzed by digestive enzymes in the gut lumen; it is absorbed across the gastrointestinal epithelium largely in its intact form, mainly by passive diffusion, and enters the portal circulation, where it undergoes extensive first-pass metabolism in the intestinal epithelium and liver before reaching the systemic circulation. Its principal molecular target, transient receptor potential vanilloid 1 (TRPV1), is upregulated in the inflamed colonic mucosa of patients with inflammatory bowel disease (IBD), a chronic relapsing disorder in which current therapies remain limited by incomplete efficacy, loss of response and cumulative toxicity. Because capsaicin activates TRPV1 on capsaicin-sensitive sensory neurons and can thereby evoke burning pain and neurogenic inflammation, its potential relevance to IBD was long overlooked. In recent years, however, a growing body of preclinical evidence has shown that capsaicin can attenuate experimental colitis through multiple pathways, including anti-inflammatory action, mucosal protection, microbiota regulation and microcirculation regulation, whereas higher doses, certain routes of administration and an already-inflamed mucosa favour adverse effects-consistent with the bell-shaped dose-response relationship reported for capsaicin. This review summarizes the evidence for the protective effects of capsaicin in IBD, outlines its gastrointestinal adverse effects and the TRPV1-dependent mechanisms that underlie them, and discusses how dose, route, duration of exposure and disease stage determine whether capsaicin acts as friend or foe.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181419","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":"A review on MMP-2 modulating agents from natural and synthetic sources and their role in inflammatory bowel disease.","authors":"Murugasamy Ragunath, Sudarsan Ardra, Akshad Balde, Rasool Abdul Nazeer","doi":"10.1007/s10787-026-02427-8","DOIUrl":"https://doi.org/10.1007/s10787-026-02427-8","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by chronic intestinal inflammation, epithelial barrier dysfunction, immune dysregulation, and aberrant extracellular matrix (ECM) remodeling. Matrix metalloproteinase-2 (MMP-2), a zinc-dependent gelatinase, has emerged as a critical regulator of intestinal homeostasis owing to its dual role in tissue repair and inflammatory tissue destruction. Unlike several inducible matrix metalloproteinases, MMP-2 is constitutively expressed and tightly regulated through interactions with membrane-type MMPs, tissue inhibitors of metalloproteinases (TIMPs), cytokines, redox signalling, and microbial factors. Dysregulated MMP-2 activity contributes to epithelial barrier disruption, leukocyte infiltration, chronic inflammation, fibrosis, and disease progression in IBD. This review summarizes the current understanding of MMP-2 biology, activation mechanisms, and immunopharmacological functions in intestinal inflammation, while critically evaluating therapeutic strategies aimed at its modulation. Particular emphasis is placed on natural and synthetic MMP-2 modulators, including animal-derived peptides and endogenous inhibitors, plant-derived polyphenols, flavonoids, alkaloids, terpenoids, and rationally designed small-molecule and peptidomimetic inhibitors. Emerging nanocarrier-based and targeted delivery systems are also discussed as approaches to enhance selectivity and minimize systemic toxicity. Furthermore, the review highlights the limitations of broad-spectrum MMP inhibition and underscores the need for site-specific modulation that preserves physiological tissue remodeling while suppressing pathological activity. Advances in precision medicine, single-cell and spatial transcriptomics, organoid-based disease models, and microbiome-informed therapeutic strategies are expected to facilitate the development of next-generation MMP-2-targeted interventions. Collectively, MMP-2 represents a promising yet complex therapeutic target whose successful modulation may improve long-term outcomes in IBD.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181290","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":"Evaluation of the anti-inflammatory potentials of ethanol leaf extract of Vigna unguiculata in Wistar rats.","authors":"Adekunle Theophilus Adegbuyi, Aziakpono Moses Omoirri, Oyepata Semeon Joseph, John Oludele Olanlokun, Paul Anton Steenkamp","doi":"10.1007/s10787-026-02423-y","DOIUrl":"https://doi.org/10.1007/s10787-026-02423-y","url":null,"abstract":"<p><strong>Background: </strong>Inflammation involves complex biological pathways, notably characterized by the overexpression of cytokines such as IL-1β, TNF-α, IL-6, IL-8, and COX-2. Inflammation is the onset of many diseases and its control will prevent several progression and complications of many diseases.This study investigates the anti-inflammatory activity of ethanol leaf extract of Vigna unguiculata in rat models, with emphasis on its effects on serum inflammatory cytokines and acute-phase reactants.</p><p><strong>Methods: </strong>Ethanol extract of Vigna unguiculata leaves was prepared and evaluated for anti-inflammatory activity using carrageenan-induced paw edema and egg albumin-induced paw inflammation models in Wistar rats. Serum levels of IL-1β, TNF-α, IL-6, IL-8, IL-10, IL-13, IFN-γ, CRP, and COX-2 were quantified using ELISA after treatment with extract doses of 100, 200, and 400 mg/kg. Indomethacin (10 mg/kg) served as the standard control. Phytochemical screening and acute toxicity testing were performed.</p><p><strong>Results: </strong>The extract significantly inhibited paw edema in a dose-dependent manner, with 400 mg/kg showing a 63.2% inhibition at 4 h post-carrageenan injection. Biomarker analysis showed significant decrease of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, IFN-γ, CRP, and COX-2) and increase of anti-inflammatory cytokines (IL-10 and IL-13) (p < 0.05 vs. control). No signs of toxicity were observed up to 2000 mg/kg.</p><p><strong>Conclusion: </strong>The anti-inflammatory activity of Vigna unguiculata may be attributed to its modulatory effects on cytokines and acute-phase reactants. This validates its traditional use and suggests potential therapeutic benefits in inflammatory diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181332","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":"Synergistic approaches to Alzheimer's disease: exploring the combined efficacy of phytoconstituents and conventional drugs.","authors":"Abhishek Kumar","doi":"10.1007/s10787-026-02417-w","DOIUrl":"https://doi.org/10.1007/s10787-026-02417-w","url":null,"abstract":"<p><strong>Background: </strong>Cognitive functions deteriorate with Alzheimer's disease (AD), a kind of degenerative disease. Problems with memory, interpersonal interactions, problem-solving, and other cognitive functions that limit a person's ability to do daily tasks are the hallmarks of dementia. This condition affects about 50 million individuals globally. Traditional therapies for AD, like galantamine, donepezil, and memantine, only offer symptomatic alleviation through glutamatergic regulation and cholinergic augmentation, making AD a significant worldwide health concern.</p><p><strong>Objective: </strong>This review assesses the possibility of improving the effectiveness of therapy by combining significant phytoconstituents with traditional AD therapies.</p><p><strong>Methods: </strong>A complete literature review was carried out using peer-reviewed publications, experimental investigations, and review papers published from 2010 to 2025. The primary objective of the investigation was to study the interaction between phytoconstituents and conventional therapy in the treatment of Alzheimer's disease.</p><p><strong>Result: </strong>Our outcomes demonstrate the powerful multi-target adjuvant properties of curcumin, resveratrol, quercetin, berberine, and luteolin. In particular, Berberine and Quercetin considerably reduce neuroinflammation and oxidative stress through the Nrf2/HO-1 and NF-κB pathways, whereas Curcumin and resveratrol enhance the anti-amyloidogenic effects of conventional medications. Additionally, luteolin exhibits a special capacity to regulate tau hyperphosphorylation, which enhances memantine's stabilising neurotransmitter actions.</p><p><strong>Discussion: </strong>The primary objective of therapy has shifted from symptomatic relief to disease modification by the synergy between phytoconstituent and conventional drugs. These combinations preserve the structural integrity of the cholinergic synapse by concurrently mitigating oxidative stress and amyloid toxicity.</p><p><strong>Conclusion: </strong>A possible paradigm shift towards holistic neuroprotection is represented by the incorporation of these five essential phytoconstituents into traditional AD regimens. To ensure clinical translatability, future research must now focus on nanoformulations that can overcome the limited bioavailability of substances like curcumin. These methods may improve treatment effectiveness, lessen adverse effects, and reduce the chance of resistance, providing a more thorough method of handling the complexities of AD.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181480","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":"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}