Pharmacological Reports最新文献

{"title":"Access to high-fat diet results in increased sensitivity to the psychostimulant effects of MDPV in mice.","authors":"Jakub Wojcieszak, Katarzyna Kuczyńska, Adrianna Leszczyńska, Eryk Naraziński, Maria Cichalewska-Studzińska","doi":"10.1007/s43440-025-00701-0","DOIUrl":"10.1007/s43440-025-00701-0","url":null,"abstract":"<p><strong>Background: </strong>The current study investigated the effects of high-fat diet on acute response to 3,4-methylenedioxypyrovalerone (MDPV) in mice. MDPV is a beta-cathinone derivative endowed with psychostimulant activity. Similarly to recreational substances, consumption of palatable food stimulates the mesolimbic dopaminergic system, resulting in neuroadaptive changes.</p><p><strong>Methods: </strong>Adolescent C57BL/6N mice were fed either control diet (CD), 10% of kcal from fat, or high-fat diet (HFD), 60% of kcal from fat. After eight weeks, one group of HFD-fed mice had their diet changed to CD for an additional two weeks. Fasting glucose levels and glucose tolerance were measured to detect impairment in glucose metabolism. Subsequently, the mice were treated with either MDPV (1 mg/kg) or saline, and their locomotor activity was measured. Using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), the expression of dopamine receptor D1 (Drd1), dopamine receptor D2 (Drd2), and FBJ osteosarcoma oncogene B (FosB) genes was measured in the striatum of mice.</p><p><strong>Results: </strong>Feeding with HFD caused obesity and glucose intolerance in mice. Restriction of fat reduced body mass and reversed impairment of glucose metabolism. HFD-fed mice responded to MDPV with higher potency than CD-fed counterparts, with an increased incidence of stereotypies. A change of diet partially reversed this effect. Downregulation of Drd2 was observed in the mice that switched from HFD to CD, whereas treatment with MDPV caused upregulation of FosB only in the CD-fed mice.</p><p><strong>Conclusions: </strong>Current results suggest that obesity may increase sensitivity to psychostimulant effects of MDPV and elevate the risk of addiction as mice fed with HFD responded to acute treatment with MDPV with higher potency and showed tolerance of FosB induction in response to the drug.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"434-449"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047437","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":"Olaparib-induced hyperglycemia in ovarian cancer patients - a case series analysis of a three-month therapy with a consideration of BMI.","authors":"Joanna Stanisławiak-Rudowicz, Edyta Szałek, Barbara Więckowska, Edmund Grześkowiak, Radosław Mądry","doi":"10.1007/s43440-025-00702-z","DOIUrl":"10.1007/s43440-025-00702-z","url":null,"abstract":"<p><strong>Background: </strong>Olaparib is a relatively new poly(ADP-ribose) polymerase inhibitor (PARPi) administered to ovarian cancer (OC) patients with a complete or partial response to first-line chemotherapy. One of the metabolic side effects of olaparib is the disruption of glucose homeostasis, often resulting in hyperglycemia The study was a retrospective analysis of olaparib-induced hyperglycemia in OC patients with initial normoglycemia following the first, second, and third month of olaparib treatment METHODS: The study involved 32 OC patients, classified into three groups according to their Body Mass Index (BMI): normal BMI (BMI 18.5-24.9 kg/m²; n = 13), overweight (BMI 25-29.9 kg/m²; n = 13), and obese (BMI ≥ 30 kg/m²; n = 6). The fasting glucose (FG) concentration was evaluated after the first, second, and third cycle of olaparib treatment (a cycle is the equivalent of 28 days of treatment). The severity of the observed hyperglycemia was assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</p><p><strong>Results: </strong>A significant increase in glycemia was observed after the first and second cycles of olaparib treatment in the group with normal BMI and after the third cycle in overweight and obese patients. There were no significant differences in glucose levels among the groups following the first, the second, and the third cycle. Grade 1 hyperglycemia with impaired fasting glucose levels (5.6-6.9 mmol/l) was found in 15 patients (normal BMI: n = 4, overweight: n = 9, and obesity: n = 2), while glycemia typical of diabetes (≥ 7.0 mmol/l) was observed in one obese patient.</p><p><strong>Conclusions: </strong>Regardless of the weight of OC patients, it is essential to control glycemia during olaparib treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"500-507"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067283","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":"Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.","authors":"Yifan Huang, Fiona Qiu, Katarzyna M Dziegielewska, Mark D Habgood, Norman R Saunders","doi":"10.1007/s43440-024-00682-6","DOIUrl":"10.1007/s43440-024-00682-6","url":null,"abstract":"<p><strong>Background: </strong>Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.</p><p><strong>Methods: </strong>Sprague Dawley rats at postnatal day P4, pregnant embryonic day E19 dams, and non-pregnant adult females were administered paracetamol (15 mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione, and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and their entry into the brain, CSF and transfer across the placenta were estimated.</p><p><strong>Results: </strong>In monotherapy, concentration of parent paracetamol in plasma, CSF, and brain remained similar and at all ages brain entry was unrestricted. In combination therapies, CSF entry of paracetamol increased following co-treatment with olanzapine. Placental transfer of parent paracetamol remained unchanged, however, transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age.</p><p><strong>Conclusions: </strong>Developmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"474-489"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032275","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":"Off-label use of anlotinib in malignancies' treatment: efficacy and management of adverse reactions.","authors":"Guangli Wang, Yuling Wang, Changhao Jin, Xiaodan Sun","doi":"10.1007/s43440-025-00700-1","DOIUrl":"10.1007/s43440-025-00700-1","url":null,"abstract":"<p><p>Anlotinib is a novel small-molecule multi-target tyrosine kinase inhibitor (TKIs) independently developed in China, it possesses the functions of inhibiting tumor angiogenesis and suppressing tumor growth. Anlotinib has achieved notable therapeutic effects in approved indications for advanced non-small cell lung cancer, soft tissue sarcoma, small cell lung cancer, and medullary thyroid carcinoma. Additionally, with unanimous expert consensus, it has been used off-label in various other tumors, yielding favorable outcomes. This article reviews the efficacy and common adverse reactions, as well as their management, of off-label use of anlotinib in various malignant tumors.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"392-408"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080762","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":"[¹¹C]MK-6884 PET imaging reveals lower M₄ muscarinic acetylcholine receptor availability following cocaine self-administration in male rats.","authors":"Krishna K Gollapelli, Ivan Krizan, Bhuvanachandra Bhoopal, Naresh Damuka, Carson Moriarty, Mack Miller, Kiran K Solingapuram Sai, Robert W Gould","doi":"10.1007/s43440-025-00695-9","DOIUrl":"10.1007/s43440-025-00695-9","url":null,"abstract":"<p><strong>Background: </strong>Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M₄ mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD. However, it is unclear how cocaine exposure affects M₄ mAChR expression or distribution.</p><p><strong>Objectives: </strong>To evaluate the effects of cocaine self-administration on M₄ mAChR availability using [¹¹C]MK-6884 in vivo PET imaging in rats that self-administered cocaine (cocaine SA) or sucrose pellets (control).</p><p><strong>Methods: </strong>Sprague-Dawley rats self-administered cocaine or sucrose pellets for 15 days under 2-h or 4-h sessions followed by PET imaging with [¹¹C]MK-6884, a radiolabeled M₄ selective positive allosteric modulator to determine the effects of cocaine on [¹¹C]MK-6884 standard uptake values with cerebellum as reference (SUVr).</p><p><strong>Results: </strong>Cumulative cocaine intake ranged between 324 and 776 mg/kg. Cocaine self-administration was associated with significantly lower [¹¹C]MK-6884 SUVrs in the cortex, hippocampus, and striatum compared to cocaine-naive rats, with a negative correlation between radiotracer SUVrs and cocaine intake in the hippocampus.</p><p><strong>Conclusions: </strong>These results suggest that cocaine self-administration decreases M₄ mAChR availability, providing further support for pursuing activation/enhancement of M₄ mAChR function as a viable pharmacotherapeutic approach for CUD.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"532-541"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979490","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":"Rebound effect, discontinuation, and withdrawal syndromes associated with drugs used in psychiatric and neurological disorders.","authors":"Aleksandra Wisłowska-Stanek, Michał Jarkiewicz, Dagmara Mirowska-Guzel","doi":"10.1007/s43440-024-00689-z","DOIUrl":"10.1007/s43440-024-00689-z","url":null,"abstract":"<p><p>Sudden cessation of the drug can cause withdrawal syndrome, discontinuation syndrome, or rebound effect. The common feature of these phenomena is a quick onset, usually limited duration depending on the drug's half-life and remission after restarting the therapy. They are characterized by varying clusters of somatic, autonomic, and psychiatric symptoms. Originally withdrawal syndrome was described for drugs with addictive properties such as barbiturates or benzodiazepines. On the other hand sudden abrupt of antidepressants or antipsychotics may cause discontinuation symptoms including movement or sensory disturbances, sleep disturbances, and hyperarousal but generally of less severity comparing to withdrawal syndrome. The aforementioned syndromes are physiologically based on the predominance of cellular counter-regulations as an effect of the sudden abrupt of a regularly taken medication. Classically the pathogenesis of withdrawal syndrome, based on physical dependence, results in life-threatening, long-lasting manifestations such as, seizures and delirium, different from the treated disease. In turn, these symptoms are not typical for discontinuation syndrome which is not considered as serious and usually spontaneously resolving. In turn, the rebound effect is clinically characterized by the relapse of the disease symptoms that are controlled by medication, but of greater severity than those before treatment.In the current review, we describe withdrawal and discontinuation syndromes associated with selected drugs used in psychiatry and neurology, risk factors, and recommendations for diminishing syndrome occurrence. Knowledge of their pathogenesis and symptoms resulting from drug discontinuation may be helpful in syndrome management and expectantly reduces the risk of diagnostic and therapeutic errors.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"303-314"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876998","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":"Efficacy of probiotic adjuvant therapy in women with major depressive disorder: insights from a case series study.","authors":"Jairo Izidro Rossetti Navarro Júnior, Rafaela Aires, Thiago Antonio de Sousa Cutrim, Elisardo Corral Vasquez, Thiago Melo Costa Pereira, Bianca Prandi Campagnaro","doi":"10.1007/s43440-024-00690-6","DOIUrl":"10.1007/s43440-024-00690-6","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic targeting of the intestinal microbiota has gained increasing attention as a promising avenue for addressing mood disorders. This study aimed to assess the potential effect of supplementing standard pharmacological treatment with the probiotic kefir in patients with Major Depressive Disorder (MDD).</p><p><strong>Methods: </strong>Thirty-eight female participants diagnosed with moderate MDD by the Hamilton Rating Scale for Depression (HAM-D) were selected to receive the probiotic kefir in conjunction with antidepressant therapy for 12 weeks. The participants were evaluated at baseline (T0) and 90 days after probiotic kefir supplementation (T90). HAM-D scores and blood samples were collected at both time points.</p><p><strong>Results: </strong>Probiotic supplementation significantly reduced MDD severity, as evidenced by lower HAM-D scores compared to baseline. Probiotic consumption for 90 days also significantly decreased interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels compared to baseline. However, probiotic kefir supplementation did not significantly affect serum serotonin levels. Additionally, after 90 days of probiotic consumption, insulin and morning cortisol levels were significantly reduced. In contrast, no significant changes were observed in serum levels of prolactin, vitamin D, and afternoon cortisol.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the potential benefits of probiotics, specifically kefir, as adjunctive therapy for female patients with MDD. The findings highlight promising results in ameliorating depressive symptoms and modulating inflammatory and hormonal markers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"463-473"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979426","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":"Exploring melatonin's signalling pathways in the protection against age-related skin deterioration.","authors":"Maryam Taheri, Farnoosh Seirafianpour, Amirali Fallahian, Azam Hosseinzadeh, Russel J Reiter, Saeed Mehrzadi","doi":"10.1007/s43440-025-00699-5","DOIUrl":"10.1007/s43440-025-00699-5","url":null,"abstract":"<p><p>Melatonin, renowned for regulating sleep-wake cycles, also exhibits notable anti-aging properties for the skin. Synthesized in the pineal gland and various tissues including the skin, melatonin's efficacy arises from its capacity to combat oxidative stress and shield the skin from ultraviolet (UV)-induced damage. Moreover, it curbs melanin production, thereby potentially ameliorating hyperpigmentation. The presence of melatonin receptors in diverse skin cell types and its documented ability to enhance skin tone, hydration, and texture upon topical administration underscores its promise as an anti-aging agent. Melatonin's protective effects likely emanate from its multifaceted characteristics, encompassing antioxidant, anti-inflammatory, and immunomodulatory functions, as well as its influence on collagen synthesis and mitochondrial activity. Chronic inflammation and oxidative stress initiate a detrimental feedback loop. Reactive oxygen species (ROS), notorious for damaging cellular structures, provoke immune responses by oxidizing vital molecules and activating signaling proteins. This triggers heightened expression of inflammatory genes, perpetuating the cycle. Such dysregulation significantly compromises the body's resilience against infections and other health adversities. This study embarks on an exploration of the fundamental signaling pathways implicated in skin aging. Furthermore, it delves into the therapeutic potential of melatonin and its anti-aging attributes within the realm of skin health.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"375-391"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067278","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":"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}