Inflammopharmacology最新文献

{"title":"Repurposing of high-dose N-acetylcysteine as anti-inflammatory, antioxidant and neuroprotective  agent  in moderate to severe traumatic brain injury patients: a randomized controlled trial.","authors":"Alaa Refaat Gouda, Noha A El-Bassiouny, Ahmad Salahuddin, Emad Hamdy Hamouda, Amira B Kassem","doi":"10.1007/s10787-025-01706-0","DOIUrl":"10.1007/s10787-025-01706-0","url":null,"abstract":"<p><strong>Introduction: </strong>Traumatic brain injury (TBI) refers to an impact of the brain within the skull resulting in an altered mental state. The study aim is to determine the effect of a high dose of N-acetylcysteine (NAC) on biochemical and inflammatory markers of neuronal damage and clinical outcomes in patients with moderate to severe TBI.</p><p><strong>Methods: </strong>A randomized open label-controlled trial was conducted on 40 patients with moderate to severe TBI patients presented to the emergency unit within < 24 h since the trauma occurred and randomized into NAC and control groups 20 patients each. Serum samples for evaluation of biomarkers: malondialdehyde (MDA), interleukin-6 (IL-6), neuron-specific enolase (NSE), and S100B were withdrawn at baseline and on day 7. The patients were followed for 7 days and evaluated clinically by the Glasgow Coma Scale (GCS).</p><p><strong>Results: </strong>There was a significant decrease in NSE and MDA levels on day 7 from baseline in NAC group (p < 0.001 and p < 0.001). Also, S100B and IL-6 decreased significantly in NAC group on day 7 from baseline (p = 0.003 and p < 0.001 consequently) compared to control group. Moreover, patients in NAC group showed a significantly shorter length of stay at intensive care unit (ICU) (p = 0.038). There was a significant increase in GCS in NAC group on day 7 from baseline (p = 0.001).</p><p><strong>Conclusion: </strong>Adjunctive early use of high-dose NAC significantly reduced inflammatory and oxidative markers and had neuroprotective effect which may be a novel treatment option for moderate to severe TBI patients.</p><p><strong>Trial registration: </strong>Pactr.org identifier: (PACTR202209548995270) on 14 September 2022.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3307-3316"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984737","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":"Chaperone-mediated autophagy, heat shock protein 70, and serotonin: novel targets of beta-hydroxybutyrate in HFFD/LPS-induced sporadic Alzheimer's disease model.","authors":"Reem A Mohamed, Dalaal M Abdallah, Hanan S El-Abhar","doi":"10.1007/s10787-025-01754-6","DOIUrl":"10.1007/s10787-025-01754-6","url":null,"abstract":"<p><p>Sporadic Alzheimer's disease (AD), which accounts for the majority of cases, is sturdily influenced by lifestyle factors such as dietary habits, obesity, and diabetes, leading to its classification as Type 3 diabetes. To model this pathological link, our AD-like model was developed by feeding Wistar male rats a high-fat diet with fructose in drinking water (HFFD) for 8 weeks, followed by a single dose of lipopolysaccharide (LPS). This group was compared with a normal control group fed a standard diet and a β-hydroxybutyrate (BHB)-treated group (125 mg/kg, p.o.), administered starting 3 h after LPS and continuing for 1 week. The results demonstrate that BHB treatment illuminated cognitive gains, as indicated by the Y-maze, Morris water maze, and novel object recognition tests. In addition, it preserved hippocampal cytoarchitecture, reduced neurodegeneration, and attenuated amyloid plaques and phosphorylated Tau deposition. Cellularly, BHB restored critical molecular mechanisms, including increased lysosomal-associated membrane protein 2A (LAMP2A) hippocampal content as the main marker of chaperone-mediated autophagy (CMA), along with the chaperon protein Hsp70. Moreover, BHB alleviated neuroinflammation by inhibiting the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome activation alongside the downstream targets cleaved caspase-1 and IL-1β/IL-18 cytokines. BHB also reduced pyroptotic markers, caspase-11 and gasdermin-N, and microglia-induced inflammation as it shifted microglial polarization toward the neuroprotective M2 phenotype. Finally, BHB normalized hippocampal neurotransmitter levels of the inhibited acetylcholine and serotonin. These findings support BHB as a promising, multifaceted treatment for AD, highlighting the roles of CMA, Hsp70, and 5-HT in slowing disease progression and improving cognitive function.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3461-3477"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998545","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 to: Anti-arthritic and immunomodulatory efficacy of Micromeria biflora Benth extract and its fractions in rats by restoring oxidative stress, metalloproteinases, pro-inflammatory and anti-inflammatory cytokines network.","authors":"Fakhria A Al-Joufi, Ambreen Malik Uttra, Sumera Qasim, Urooj Iqbal, Nabeela Tabassum Sial, Noura M Alhumaid","doi":"10.1007/s10787-024-01579-9","DOIUrl":"10.1007/s10787-024-01579-9","url":null,"abstract":"","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3509-3510"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590793","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":"Anti-arthritic potential and mechanistic insights of methanol extract of Rhamnus prinoides Engl. in complete Freund's adjuvant-induced rats.","authors":"James Kimani Kamau, Mathew Piero Ngugi, Joseph N Ngeranwa","doi":"10.1007/s10787-025-01770-6","DOIUrl":"10.1007/s10787-025-01770-6","url":null,"abstract":"<p><p>This study determined the phytochemical profile and in vivo anti-arthritic potential and mechanistic effects of MeOH extract of Rhamnus prinoides. The liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used in the phytochemical analysis of the extract. In the anti-arthritic assay, the rats were assigned into arthritic control, non-arthritic control, methotrexate control, and three extract-treated [100, 200, and 300 mg/kg body weight (bw)] groups. Complete Freund's adjuvant was used to induce polyarthritis. The treatments were orally administered from day 8 post-induction of polyarthritis. The experimental animals were euthanized and blood was drawn for hematological parameter analysis on day 29. The ankle joint tissue and liver were detached and utilized in gene expression using RT-qPCR and standard antioxidant assays, respectively. One-factorial ANOVA and Tukey's multiple comparisons were used to compute for statistical differences of the raw data. The LC-MS analysis identified phytochemicals of flavonoids, anthraquinones, lignans, and coumarins classes. Fatty acid methyl ester, benzofuran, and terpene were also detected using GC-MS. The extract significantly reduced ankle joint edema, reduced body weight loss and arthritis scores, improved elevated spleen and thymus indices, attenuated aberrant hematological parameters, lowered malonaldehyde levels, and enhanced enzymatic antioxidant activities in rats induced with polyarthritis (p < 0.05). The extract also significantly upregulated expression of I-κBα, IL-4, and IL-10 genes, as well as downregulated expression of STAT-3, NF-κB, RANKL, COX-2, TNF-α, and IL-6 genes in rats induced with polyarthritis (p < 0.05). The extract possesses phytochemicals with anti-arthritic potential and can be used as a potential lead in developing novel anti-arthritic agents.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3195-3211"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994593","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":"Phytochemical analysis of leaf extract of Piper nigrum and investigation of its biological activities.","authors":"Pankaj Barman, Srija Hazarika, Kallol Roy, Ravindra K Rawal, Rituraj Konwar","doi":"10.1007/s10787-025-01701-5","DOIUrl":"10.1007/s10787-025-01701-5","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the phytoconstituents of the less explored leaf of Piper nigrum, a common ethnomedicinal plant as an alternate source for multiple bioactivities.</p><p><strong>Methods: </strong>Hydro-ethanolic (1:4) extract of Piper nigrum leaves (PNLE) prepared and profiled using liquid chromatography and mass spectrometry for identification of phytomolecules. Anti-oxidant activity, intracellular reactive oxygen species (ROS) expression, phagocytosis activity, and cytokine expression were estimated using cell-free and cell-based assays. Anti-cancer activity was determined with cancer cell viability, migration inhibition and colony-formation assay. Apoptosis and membrane depolarization assay were done using fluorescent microscopic staining methods while network pharmacology, and molecular docking analysis were done using open source and online tools.</p><p><strong>Results: </strong>Major phytomolecules identified in PNLE were pentanamide N,N-didecyl, piperettine, curcumin, myristicin, pipernonaline, sesamin, and lupenone. PNLE exhibited anti-bacterial activity with higher activity against Gram-positive bacteria, Staphylococcus aureus. PNLE also showed anti-oxidant and anti-inflammatory activity through neutralization of free radicals; inhibition of intracellular ROS generation; inhibition of phagocytosis and reduction of cytokine (IL-6 and TNF-α) levels. PNLE showed anti-proliferative activity against human breast cancer cells (MDA-MB-231), rat mammary tumor cells (LA7), and mouse melanoma cells (B16-F10) with highest activity against MDA-MB-231 cells. The extract did not inhibit human kidney cells (HEK-293). Further, PNLE treatment significantly inhibited cell migration and colony formation of MDA-MB-231 cells. Fluorescent staining techniques confirmed induction of apoptosis in cancer cells by PNLE. Further, network pharmacology and molecular docking studies revealed that the identified PNLE phytomolecules share 97 targets of out of potential breast cancer and inflammation-related target genes with four best common target proteins among the top hub genes and sesamin showed the highest binding affinity with these important cellular targets.</p><p><strong>Conclusions: </strong>Overall, the phytochemical profile of PNLE showed clear presence of important phytomolecules and their association with critical human cellular mechanistic pathways responsible for exhibited bioactivities. This study further establishes the leaf of P. nigrum as an additional anatomical plant part with potent medicinal properties and  as a potential renewable source for bioactive phyomolecules.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3255-3277"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020566","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":"Role of mGluR7 in Alzheimer's disease: pathophysiological insights and therapeutic approaches.","authors":"Garry Hunjan, Khadga Raj Aran","doi":"10.1007/s10787-025-01765-3","DOIUrl":"10.1007/s10787-025-01765-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by oxidative stress, mitochondrial dysfunction, synaptic impairment, and neuronal loss. The progression of AD depends on two main pathologic features, amyloid-beta accumulation, and tau pathology, whereas the disruption of glutamatergic neurotransmission plays an essential role in disease progression. Glutamate, the brain's primary excitatory neurotransmitter, acts on ionotropic and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptor 7 (mGluR7) is a pre-synaptic type III mGluR receptor playing a crucial role in the central nervous system (CNS) through neurotransmitter modulation, reducing glutamate-induced excitotoxicity, and promoting early neuronal growth. Since mGluR7 is a key regulator of neurotransmitter release, it modulates synaptic integrity and neuronal survival, and its dysfunction is associated with impaired synaptic homeostasis in AD. Moreover, mGluR7 interacts with neuroinflammatory pathways by activating microglia and regulating cytokine production, therefore playing a significant role in AD pathogenesis. The drugs targeting mGluR7, including mGluR7 agonists, antagonists, and allosteric modulators, could potentially be among the most effective agents for the treatment of psychiatric disorders, neurodegenerative diseases including AD, as well as neurodevelopmental impairments, though these potential therapies remain in the early stages. This article summarises the structure as well as the function of mGluR7 and explores current insights into the functioning of mGluR7 in molecular mechanisms of AD pathogenesis. It also discusses potential therapeutic targets of mGluR7, highlighting the need to develop such therapies to prevent disease progression.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"2977-2995"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013128","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":"Dapagliflozin targets the crosstalk between apoptosis, autophagy, and Hedgehog signaling pathways through AMPK activation in the adjuvant-induced arthritic rat model.","authors":"Aya A El-Demerdash, Samar F Darwish, Marwa O El-Derany, Ebtehal El-Demerdash","doi":"10.1007/s10787-025-01750-w","DOIUrl":"10.1007/s10787-025-01750-w","url":null,"abstract":"<p><p>Rheumatoid arthritis is a long-term autoimmune disorder, causes joint capsule, cartilage, and bone damage. Dapagliflozin, a novel antidiabetic drug, demonstrated promising effects against different disorders. Herein, we aimed to detect the dose-dependent antiarthritic impact of dapagliflozin alone and in combination with methotrexate standard treatment. Complete Freund's adjuvant-induced arthritic rats were treated with three doses of dapagliflozin (1, 5, or 10 mg/kg/day, p.o.) for 3 weeks, in which 10 mg dose showed eminent anti-arthritic effects according to gait score, paw diameter, arthritic index (AI), morphological and histological results. To reveal dapagliflozin mechanism, locomotor, biochemical, and histological measures were assessed in dapagliflozin (10 mg/kg/day) and/or methotrexate (0.75 mg/kg/week, i.p.)-treated arthritic rats. Radiography and histology confirmed the prominent anti-arthritic effect of dapagliflozin via reduced RF, MMP-1, and MMP-3, and improved gait score, ankle diameter, and AI. Anti-inflammatory impact was confirmed by the downregulation of TNF-α, IL-1β, IL-6, and NF-κb p65 expression. Upregulation of autophagy was detected through; Beclin-1, ULK-1, and ATG-7, in dapagliflozin treated arthritic rats. Furtherly, dapagliflozin stimulated apoptotic activity, by boosting articular levels of CASP-3, CASP-9, cartilage gene expression of p53, and Bax/Bcl₂ ratio. Interestingly, dapagliflozin upregulates p-AMPK/t-AMPK articular activity. Additionally, dapagliflozin inhibited the Hedgehog signaling pathway, through the downregulation of cartilage Shh, ptch1, Smo, and Gli-1 expression. Dapagliflozin/methotrexate combination therapy exhibited greater anti-arthritic benefits compared to methotrexate alone. These data highlight dapagliflozin as an anti-rheumatic drug, either alone or with methotrexate.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3157-3176"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965389","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":"Phytochemical studies of Gerbera jamesonii and evaluation of anti-inflammatory potential in formaldehyde-induced arthritis in rats.","authors":"Malik Saad Ullah, Ateeq Amjad, Zunera Chauhdary, Uzma Saleem, Naheed Akhtar","doi":"10.1007/s10787-025-01720-2","DOIUrl":"10.1007/s10787-025-01720-2","url":null,"abstract":"<p><p>In plants, numerous intricate and structurally diverse phytochemicals are found naturally. The adoption of traditional herbal medicines for many ailments in recent years has prompted researchers to look into the medicinal properties of numerous plants. Although the Asteraceae family has a wide range of significant pharmacological benefits, its antioxidant and antibacterial properties are the most significant. The goal of this study was to ascertain the phytochemical profiling and investigation of anti-arthritic pursuits of Gerbera jamesonii. GC-MS analysis was performed to screen the fingerprints of bioactive compounds. The efficacy of ethanol extract against formaldehyde-induced inflammation in rats was assessed in an in vivo investigation using oral doses of 250-, 500- and 800 mg/kg. The study lasted for 29 days, Hematological and biochemical evaluations were conducted on blood and serum samples. Gerbera jamesonii ethanolic extract (GJE) extract treatment dose dependently decreased the paw inflammation, paw diameter and arthritic score. GJE treatment downregulated the mRNA and protein expression of inflammatory cytokines. Radiological and histo-pathological assessments revealed that GJE treatment effectively reversed the histological and radiological alterations induced by formaldehyde exposure, demonstrating a significant recovery. In the light of above findings, it is suggested that Gerbera jamesonii might be useful in the treatment of inflammatory diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3213-3231"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772245","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":"Voclosporin promotes neurological function recovery by inhibiting inflammation and maintaining blood-brain barrier integrity following rtPA reperfusion after MCAO in mice.","authors":"Yangmin Zheng, Shubei Ma, Wei Sun, Feng Yan, Yumin Luo","doi":"10.1007/s10787-025-01757-3","DOIUrl":"10.1007/s10787-025-01757-3","url":null,"abstract":"<p><p>Hemorrhagic transformation (HT) is the most serious complication after rtPA thrombolytic therapy in patients with acute ischemic stroke, which greatly limits the clinical application of rtPA. rtPA disruption of the blood-brain barrier (BBB) by inducing inflammation after cerebral ischemia may be an important mechanism for the development of HT, and maintaining BBB integrity can significantly reduce the risk of HT. Our study found that a new generation of calcineurin inhibitors, voclosporin can improve neurological function, reduce neuronal damage, and reduce cerebral infarction volume in mice. By Evans blue extravasation assay and cerebral water content measurement, it was found that voclosporin could improve BBB injury and reduce brain edema caused by rt-PA. The ELISA and immunofluorescence experiments further proved that voclosporin can reduce the expression of IL-1β/TNF-α, increase the expression of IL-10/IL-4, and protect the integrity of the BBB by promoting microglia/macrophage to M2 type polarization, providing new thinking for clinical rtPA combined therapy to alleviate BBB damage.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3317-3328"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985152","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":"Clinical study evaluating the efficacy and safety of Cilostazol as an adjuvant therapy to methotrexate on patients with rheumatoid arthritis.","authors":"Samar M Eldadamony, Sahar M El-Haggar, Abdel Moaty A Ali, Tarek M Mostafa","doi":"10.1007/s10787-025-01782-2","DOIUrl":"10.1007/s10787-025-01782-2","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to assess the safety as well as effectiveness of Cilostazol as a complementary therapy to methotrexate among individuals with active rheumatoid arthritis.</p><p><strong>Method: </strong>This study was a randomly allocated, double-blind, placebo-controlled parallel design involving 70 patients who were diagnosed with active rheumatoid arthritis. Participants were randomly assigned to two sets: the control group (n = 35) which received methotrexate \"MTX\" (7.5 mg IM weekly) plus placebo tablets twice daily and the Cilostazol group (n = 35), which received the same MTX\" dose plus Cilostazol 50 mg twice daily for 3 months. Patients were assessed to determine the serum levels of C-reactive protein (CRP) nuclear factor kappa B (NF-κB), hemoxygenase-1 (HO-1), and cyclic adenosine monophosphate (cAMP). Disease Activity Score (DAS28-CRP), Multidimensional Health Assessment Score (MDHAQ), and morning stiffness duration were also assessed.</p><p><strong>Results: </strong>The Cilostazol group produced a significant improvement in cAMP level as compared to the control group (P = 0.001). cAMP level showed a significant inverse correlation with DAS28-CRP (r = -0.336; P = 0.004). However, Cilostazol group produced non-significant improvements in the serum levels of the other biological markers (CRP, NF-κB, and HO-1), DAS28-CRP score, MDHAQ score, and morning stiffness duration as compared to the control group (P > 0.05). The implication of Cilostazol for patients with rheumatoid arthritis was tolerable and safe.</p><p><strong>Conclusion: </strong>The beneficial effect of Cilostazol on cAMP and the negative correlation between cAMP and DAS28-CRP could support its impact on the disease activity. Further research seems necessary to elucidate the mechanisms underlying the link between cAMP and disease activity.</p><p><strong>Trial registration: </strong>Clinical Trials.gov identifier: NCT05594680, The date of registration is: 30/10/2022.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3499-3508"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086194","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}