Pharmacological Reports最新文献

{"title":"Effects of COVID-19 and medication used for treatment and symptom prevention on the antioxidant status.","authors":"Laura A Borba, Getúlio Antonio de Freitas Filho, Taiane de Azevedo Cardoso, Camila O Arent, Flávia S Niero, Lucas C Pedro, Caion A Rodrigues, Lara R Cichella, Margarete D Bagatini, Gabriela Gonçalves de Oliveira, Gilnei Bruno da Silva, Daiane Manica, Zuleide Maria Ignácio, João Quevedo, Luciane B Ceretta, Gislaine Z Réus","doi":"10.1007/s43440-025-00696-8","DOIUrl":"10.1007/s43440-025-00696-8","url":null,"abstract":"<p><strong>Background: </strong>It is known that an inflammatory response plays a key role in COVID-19 pathogenesis. An exacerbated inflammatory response can increase oxidative stress in cells. This study aimed to investigate the effects of COVID-19 on parameters of oxidative stress including non-protein thiol antioxidants (NPSH), protein thiols (PSH), total antioxidant capacity (TAC), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), ascorbic acid, and reactive oxygen species (ROS) in plasma collected four to six weeks after the diagnosis.</p><p><strong>Methods: </strong>This cross-sectional study included a sex-matched sample of 296 adult individuals with 112 positives (cases) and 184 negatives (controls) for COVID-19. Oxidative stress parameters were peripherally analyzed according to previous methods.</p><p><strong>Results: </strong>The results showed a decrease in NPSH (p = 0.004), TAC (p = 0.005), ROS (p < 0.001), and ascorbic acid (p < 0.001) in cases. TBARS were higher in moderate and severe cases of COVID-19 compared to asymptomatic and mild cases (p = 0.049). AOPP, PSH, and MPO were not significantly different between cases and controls. In the total sample, individuals who self-reported using medication to prevent or treat COVID-19 showed decreased NPSH (p = 0.034), TAC (p = 0.020), ascorbic acid (p = 0.010), and ROS (p = 0.001) compared to those who self-reported not using medication to prevent or treat COVID-19.</p><p><strong>Conclusions: </strong>In conclusion, individuals with COVID-19 had decreased antioxidant status. Furthermore, disease severity was associated with more lipid damage. Antioxidant therapies may be essential to prevent the impacts of COVID-19.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"490-499"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory effects of resveratrol on nitric oxide signaling in cardiovascular diseases.","authors":"Sajad Abolfazli, Sercan Karav, Thomas P Johnston, Amirhossein Sahebkar","doi":"10.1007/s43440-025-00694-w","DOIUrl":"10.1007/s43440-025-00694-w","url":null,"abstract":"<p><p>Cardiovascular illnesses are multifactorial disorders and represent the primary reasons for death worldwide, according to the World Health Organization. As a signaling molecule, nitric oxide (NO) is extremely permeable across cellular membranes owing to its unique molecular features, like its small molecular size, lipophilicity, and free radical properties. Some of the biological effects of NO are vasodilation, inhibition in the growth of vascular smooth muscle cells, and functional regulation of cardiac cells. Several therapeutic approaches have been tested to increase the production of NO or some downstream NO signaling pathways. The health benefits of red wine are typically attributed to the polyphenolic phytoalexin, resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is found in several plant species. Resveratrol has beneficial cardiovascular properties, some of which are mediated through endothelial nitric oxide synthase production (eNOS). Resveratrol promotes NO generation from eNOS through various methods, including upregulation of eNOS expression, activation in the enzymatic activity of eNOS, and reversal of eNOS uncoupling. Additionally, by reducing of oxidative stress, resveratrol inhibits the formation of superoxide and inactivation NO, increasing NO bioavailability. This review discusses the scientific literature on resveratrol's beneficial impact on NO signaling and how this effect improves the function of vascular endothelium.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"355-374"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus and diabetic rodent models.","authors":"Minyan Qian, Mengmeng Guan, Liying Wang, Nan Hu","doi":"10.1007/s43440-024-00693-3","DOIUrl":"10.1007/s43440-024-00693-3","url":null,"abstract":"<p><p>Tacrolimus (TAC) is an immunosuppressant widely utilized in organ transplantation. One of its primary adverse effects is glucose metabolism disorder, which significantly increases the risk of diabetes. Investigating the molecular mechanisms underlying TAC-induced diabetes is essential for developing effective prevention and treatment strategies for these adverse effects. In addition, TAC can induce cost-effective, non-obese animal models of diabetes, where the metabolic parameter changes closely resemble those observed during the onset and progression of type 2 diabetes (T2DM), post-transplantation diabetes mellitus (PTDM), and associated complications. This review, based on articles indexed in PubMed up to August 19, 2024, identified 48 studies focusing on TAC-induced diabetic rodent models and 22 studies exploring the effects of TAC on diabetic or obese rodent models. These studies were systematically summarized based on TAC dosage, route of administration, duration of administration, and glucose metabolism indices used for evaluation. Additionally, the impact of TAC dose reduction or discontinuation on glucose metabolism was assessed, along with pharmacological agents that modulate TAC-induced diabetes, including anti-diabetic medications, anti-inflammatory and antioxidant compounds, biologics, and antibiotics. Key signaling pathways implicated in TAC-induced diabetes include CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad, all of which impair islet β-cell function, thereby contributing to diabetes development. This review provides a concise summary of the characteristics of relevant murine models, offering valuable guidance for selecting appropriate and economical animal models for future research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"333-354"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of risedronate and its regioisomers synthesized via microwave-assisted method: bone affinity, cytotoxicity, permeability, and therapeutic potential.","authors":"Monika Zielińska, Amanda Pacholak, Bartosz Orwat, Mariusz Sandomierski, Ireneusz Kownacki, Ewa Kaczorek, Adam Voelkel","doi":"10.1007/s43440-025-00703-y","DOIUrl":"10.1007/s43440-025-00703-y","url":null,"abstract":"<p><strong>Background: </strong>Bisphosphonates (BPs) are widely used for treating bone diseases such as osteoporosis due to their strong affinity for hydroxyapatite (HA) in bones. Minor structural variations among BPs can significantly affect their therapeutic potential. This study aimed to synthesize risedronate (RSD) and its two regioisomers (2-RSD, 4-RSD) and investigate the impact of these variations on bone affinity, permeability, and cytotoxicity.</p><p><strong>Methods: </strong>RSD and its regioisomers were synthesized using a microwave-assisted method. Bone affinity was assessed through sorption studies on HA and two polymer-ceramic materials mimicking bone properties. Compound permeability was predicted using the Parallel Artificial Membrane Permeability Assay (PAMPA). Cytotoxicity was evaluated by analyzing the response of bacterial cells to BPs using metabolic activity assays.</p><p><strong>Results: </strong>2-RSD demonstrated a higher bone affinity and similar permeability than commercially available RSD. 2-RSD also showed reduced cytotoxicity in bacterial cell assays, indicating enhanced biocompatibility. These findings suggest that minor structural changes can lead to significant differences in therapeutic efficacy.</p><p><strong>Conclusions: </strong>The study highlights the potential of the 2-RSD as a more effective treatment for bone diseases. Structural variations in BPs can greatly influence their biological properties, paving the way for the development of improved therapeutic agents.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"517-531"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in the study of anti-tumor effects and mechanisms of vitexin.","authors":"Qiming Yang, Rui Huan, Defeng Meng, Junwei Qi, Lei Xia","doi":"10.1007/s43440-024-00664-8","DOIUrl":"10.1007/s43440-024-00664-8","url":null,"abstract":"<p><p>Vitexin (apigenin-8-C-beta-D-glucopyranoside) is a natural flavonoid derivative with anti-cancer, antioxidant, anti-inflammatory, antihypertensive, anti-asthma, anti-epilepsy, and other therapeutic effects. It is extracted from pearl millet, hawthorn, pigeon bean, mung bean, and other medicinal plants. Vitexin has received widespread attention because of its significant anti-tumor effect. It induces apoptosis and anti-tumor angiogenesis, inhibits tumor cell migration and invasion, regulates tumor cell autophagy and immunity, and increases patient sensitivity to radiotherapy and chemotherapy. It has a significant anti-tumor effect on breast, prostate, liver, cervical, and colon cancers, gliomas, and other malignant tumors. This review demonstrates the latest research progress on the anti-tumor effects and potential mechanisms of vitexin. It summarizes its anti-tumor mechanism to provide new theoretical support and reference for cancer treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"124-134"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hydrogen sulphide-releasing non-steroidal anti-inflammatory, ATB-346, significantly attenuates human myometrial contractions.","authors":"Ana Mijušković, Susan Wray, Sarah Arrowsmith","doi":"10.1007/s43440-024-00643-z","DOIUrl":"10.1007/s43440-024-00643-z","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous preterm birth is the leading cause of perinatal morbidity and mortality. Tocolytics are drugs used to inhibit uterine contractions in cases of imminent preterm birth, however, few are effective in stopping labour once initiated and all have side effects. Combination approaches involving drugs that target multiple signalling pathways that regulate contractions may increase efficacy, reduce dosage and improve tolerability. Both non-steroidal anti-inflammatory drugs (NSAIDs) and hydrogen sulphide (H₂S)-releasing compounds can reduce myometrial contractions. In a novel approach we evaluated the tocolytic properties of ATB-346-a H₂S-releasing derivative of the NSAID naproxen, shown clinically to reduce pain and inflammation in arthritis.</p><p><strong>Methods: </strong>Using organ baths, paired strips of human myometrium were exposed to increasing concentrations of ATB-346, or equimolar concentrations (10µM and 30µM) of the parent drug, naproxen, or the H₂S-releasing moiety, 4-hydroxy-thiobenzamide (TBZ), alone. The ability of ATB-346 versus the individual components of ATB-346 to decrease ex vivo spontaneous contractions was investigated, and the potency was compared to a known H₂S donor, Na₂S.</p><p><strong>Results: </strong>Acute application of Na₂S produced a concentration-dependent decrease in force amplitude and force integral (area under the curve) of contraction. ATB-346 produced a more profound decrease in contraction compared to equimolar concentrations of naproxen or TZB alone and was more potent than the equivalent concentration of Na₂S.</p><p><strong>Conclusions: </strong>ATB-346 exhibits potent tocolytic properties in human myometrium. These exciting results call for further exploration of ATB-346, with a view to repurposing this or similar drugs as novel therapies for delaying preterm labour.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"287-294"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency.","authors":"Łukasz Gąsior, Bartłomiej Pochwat, Monika Zaręba-Kozioł, Jakub Włodarczyk, Andreas Martin Grabrucker, Bernadeta Szewczyk","doi":"10.1007/s43440-024-00681-7","DOIUrl":"10.1007/s43440-024-00681-7","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical studies have shown that dietary zinc deficiency can lead to symptoms similar to those observed in major depressive disorder (MDD). However, the underlying molecular mechanisms remain unclear. To investigate these mechanisms, we examined proteomic changes in the prefrontal cortex (PFC) and hippocampus (HP) of rats, two critical brain regions implicated in the pathophysiology of depression.</p><p><strong>Methods: </strong>Rats were fed diets either adequate in zinc (ZnA, 50 mg Zn/kg) or deficient in zinc (ZnD, <3 mg/kg) for four weeks. High-throughput proteomic analysis was used to detect changes in protein expression, supplemented by enzyme activity assay for mitochondrial complexes I and IV, examining their functional impacts.</p><p><strong>Results: </strong>ZnD led to significant alterations in protein expression related to zinc transport and mitochondrial function. Proteomic analysis revealed changes in zinc transporter family members such as Slc30a1 (6.64 log2FC), Slc30a3 (-2.32 log2FC), Slc30a4 (2.87 log2FC), Slc30a5 (5.90 log2FC), Slc30a6 (1.50 log2FC), and Slc30a7 (2.17 log2FC) in the PFC, and Slc30a3 (-1.02 log2FC), Slc30a5 (-1.04 log2FC), and Slc30a7 (1.08 log2FC) in the HP of rats subjected to ZnD. Furthermore, ZnD significantly affected essential mitochondrial activity proteins, including Atp5pb (3.25 log2FC), Cox2 (2.28 log2FC), Atp5me (2.04 log2FC), Cyc1 (2.30 log2FC), Cox4i1 (1.23 log2FC), Cox7c (1.63 log2FC), and Cisd1 (1.55 log2FC), with a pronounced decrease in complex I activity in the PFC.</p><p><strong>Conclusions: </strong>Our study demonstrates that ZnD leads to significant proteomic changes in the PFC and HP of rats. Specifically, ZnD alters the expression of zinc transporter proteins and proteins critical for mitochondrial function. The significant decrease in complex I activity in the PFC further underscores the impact of ZnD on mitochondrial function. These results highlight the molecular mechanisms by which ZnD can influence brain function and contribute to symptoms similar to those observed in depression.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"145-157"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel fluorinated cannabinoid analogs modulate cytokine expression in human C20 microglial cells.","authors":"Randall L Davis, Sascha Grotjahn, Burkhard Koenig, Daniel J Buck, Jimmie D Weaver","doi":"10.1007/s43440-024-00680-8","DOIUrl":"10.1007/s43440-024-00680-8","url":null,"abstract":"<p><strong>Background: </strong>Phytochemicals derived from the plant Cannabis sativa hold promise in terms of medicinal value. Cannabinoids such as Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) are arguably the best characterized and known to possess wide-ranging therapeutic benefits. The mechanism of action for these therapeutic effects remains to be fully elucidated, however, the anti-inflammatory actions are of particular interest. Maximizing therapeutic effects while limiting adverse effects is crucial in pharmaceutical development. Fluorination of natural products often yields molecules with enhanced biological properties and provides opportunities for intellectual property protection not available to the natural product.</p><p><strong>Methods: </strong>Herein, we describe four novel cannabinoids (a deoxy trifluoroCBN analog (F₃CBN), the racemic cis-deoxy-trifluoro-THC (F₃THC), and truncated pyridine analogs of an intermediate in route to the THC and CBN, SG126 and SG154. Importantly, we provide the initial assessment of the biologic activity of these molecules, by investigating the in vitro effects on metabolic activity (via 3-[4,5-dimethylthiazol-2-yl]-2,5,-diphenyltetrazolium bromide, MTT assay) and cytokine expression (via enzyme linked immunosorbent assay, ELISA) in human C20 microglial cells.</p><p><strong>Results: </strong>The cannabinoids examined had minimal to no effect on metabolic activity up to 10 µM. Notably, F₃CBN and F₃THC potentiated interleukin-1 β (IL-1β)-induced expression of interferon-γ inducible protein 10 (CXCL10) and IL-6 expression whereas, SG126 and SG154 were inhibitory.</p><p><strong>Conclusions: </strong>These findings are foundational for new lines of investigation into the therapeutic potential of four novel fluorinated cannabinoids.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"295-301"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced pharmacological and pharmacokinetic evaluation of 1,3 dimethylpurine-2,6-dione derivative (GR-14) with prominent mood-modulating activity in rats.","authors":"Agnieszka Cios, Grażyna Chłoń-Rzepa, Magdalena Jastrzębska-Więsek, Krzysztof Pociecha, Katarzyna Wójcik-Pszczoła, Elżbieta Pękala, Anna Wesołowska","doi":"10.1007/s43440-024-00686-2","DOIUrl":"10.1007/s43440-024-00686-2","url":null,"abstract":"<p><strong>Background: </strong>Research on new candidates for antidepressant/anxiolytic drugs from the long-chain arylpiperazines (LCAPs) group containing a 1,3-dimethylpurine-2,6-dione as a terminal amide fragment fits into the modern exploration trend. This study aimed to examine, for the first time in male Wistar rats, pharmacodynamic (antidepressant- and anxiolytic-like) and pharmacokinetic properties of 7-(5-(4-(3-chlorophenyl)piperazin-1-yl)pentyl)-1,3-dimethyl-3,7-dihydro-1 H-purine-2,6-dione hydrochloride (GR-14).</p><p><strong>Methods: </strong>Antidepressant- and anxiolytic-like activities have been assessed in the forced swim test (FST) and Vogel conflict drinking test, respectively. The pharmacokinetic characteristics of GR-14, its distribution into rat tissues, and several in vitro ADME-Tox parameters (hepatocytotoxic, neurocytotoxic, metabolic stability) have been defined.</p><p><strong>Results: </strong>GR-14 produces strong and dose-dependent antidepressant- and anxiolytic-like effects in both tests used. Pharmacokinetic findings demonstrate that GR-14 reveals linear pharmacokinetics tested after intravenous (iv) and was rapidly absorbed after oral (po) administration. It rapidly crosses the blood-brain barrier (BBB) which is vital for therapeutic effects in vivo in psychiatric diseases, depression, and anxiety. Moreover, it is slowly eliminated from the brain, maintaining concentrations higher than those in plasma at the last time point measured. Further studies have also shown that GR-14 is an average high-clearance drug in rat liver microsomes and exerts neither hepatocytotoxic nor neurocytotoxic effects in vitro.</p><p><strong>Conclusion: </strong>The tested derivative GR-14 presents prominent mood-modulating activity in rats and has promising pharmacokinetic parameters and a good safety profile. The beneficial pharmacology and pharmacokinetics of GR-14 in vivo are in high concordance with its profile in vitro, thus underlining very hopeful properties to support the early development process.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"158-171"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities.","authors":"Fatemeh Askarizadeh, Sercan Karav, Tannaz Jamialahmadi, Amirhossein Sahebkar","doi":"10.1007/s43440-024-00678-2","DOIUrl":"10.1007/s43440-024-00678-2","url":null,"abstract":"<p><p>Statins are widely utilized to reduce cholesterol levels, particularly in cardiovascular diseases. They interface with cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase enzyme. Besides their primary effect, statins demonstrate anti-inflammatory and immune-modulating properties in various diseases, highlighting the pleiotropic effect of these drugs. The CD40:CD40L signaling pathway is considered a prominent inflammatory pathway in multiple diseases, including autoimmune, inflammatory, and cardiovascular diseases. The findings from clinical trials and in vitro and in vivo studies suggest the potential anti-inflammatory effect of statins in modulating the CD40 signaling pathway and downstream inflammatory mediator. Accordingly, as its classic ligand, statins can suppress immune responses in autoimmune diseases by inhibiting CD40 expression and blocking its interaction with CD40L. Additionally, statins affect intracellular signaling and inhibit inflammatory mediator secretion in chronic inflammatory diseases like asthma and autoimmune disorders such as myasthenia gravis, multiple sclerosis, systemic lupus erymanthus, and cardiovascular diseases like atherosclerosis. However, it is essential to note that the anti-inflammatory effect of statins may vary depending on the specific type of statin used. In this study, we aim to explore the potential anti-inflammatory effects of statins in treating inflammatory diseases by examining their role in regulating immune responses, particularly their impact on the CD40:CD40L signaling pathway, through a comprehensive review of existing literature.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"43-71"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}