BMC Pharmacology & Toxicology最新文献

{"title":"Neuroprotective potential of esterified indole-3-propionic acid with curcumin against high glucose stress: targeting oxidative damage, Akt/mTOR, and BDNF/TrkB pathways.","authors":"Jayanthi Sidhambaram, Chitra Loganathan, Penislusshiyan Sakayanathan, Palvannan Thayumanavan","doi":"10.1186/s40360-026-01153-9","DOIUrl":"10.1186/s40360-026-01153-9","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) is increasingly linked to neurodegenerative changes driven by oxidative stress, mitochondrial dysfunction, and dysregulated signaling pathways, particularly under chronic hyperglycemia.</p><p><strong>Aim: </strong>This study aimed to assess the neuroprotective effects of novel curcumin-indole-3-propionic acid conjugate (CUR-IPA) against high glucose (HG)-induced damage in SH-SY5Y neuronal cells.</p><p><strong>Methods: </strong>Cells were exposed to HG to simulate diabetic stress and co-treated with CUR-IPA (6.25-25 µM). Cell viability, oxidative stress markers, mitochondrial membrane potential (MMP), and apoptosis were evaluated. Flow cytometry was used to quantify the expression of apoptotic (p53, Bax, caspase-3, and Bcl-2), survival (p-Akt and mTOR), and neurotrophic (BDNF, p-TrkB, and CREB) proteins.</p><p><strong>Results: </strong>HG induced oxidative stress, loss of MMP, apoptosis, and suppression of PI3K/Akt/mTOR and BDNF/TrkB/CREB pathways.</p><p><strong>Conclusion: </strong>In conclusion, CUR-IPA demonstrates strong neuroprotective potential under HG stress by modulating redox status, mitochondrial function, and survival signaling. The findings suggest its promise as a multi-target therapy for diabetes-linked neurodegeneration, and warrant an in vivo study.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154899","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":"Lycopene ameliorates acrylamide-induced reproductive toxicity through enhancement in testicular antioxidant status and upregulation of androgen receptor expression in male Wistar rats.","authors":"Great Oluwamayokun Adebodun, Tirenimioluwa Blessings Obabolujo, Praise Ebunoluwa Adesope, Emmanuella Onyeacholem, Yinusa Raji","doi":"10.1186/s40360-026-01154-8","DOIUrl":"10.1186/s40360-026-01154-8","url":null,"abstract":"<p><strong>Background: </strong>Acrylamide (ACR), a food contaminant, has been reported to exert adverse effects on the male reproductive system through increased oxidative stress and hormonal imbalance. This study aimed to investigate the ameliorative potentials of lycopene on reproductive parameters, oxidative stress, and expression of androgen receptors in acrylamide-induced reproductive toxicity in male Wistar rats.</p><p><strong>Methods: </strong>Thirty-five male Wistar rats were randomly divided into seven groups (n = 5). Groups I-VII were orally administered distilled water, olive oil, acrylamide (10 mg/kg), lycopene (5 mg/kg), lycopene (20 mg/kg), acrylamide+lycopene (5 mg/kg), and acrylamide+lycopene (20 mg/kg), respectively, for 8 weeks. Following the end of the experiment, the animals were fasted overnight, weighed, and euthanized. Blood was collected, centrifuged, and serum obtained. The testes were collected and used for sperm, biochemical, and immunohistochemical analyses.</p><p><strong>Results: </strong>The results revealed that acrylamide administration decreased sperm quality, resulted in oxidative stress, hormonal imbalance, and reduced testicular androgen expression. However, lycopene significantly increased sperm count, viability, motility, serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone levels. Also, reduced testicular oxidative stress markers, decreased malondialdehyde (MDA), and enhanced antioxidant enzymes, increased superoxide dismutase (SOD) and catalase activities were observed following lycopene administration. Treatment with lycopene upregulated the expression of testicular androgen receptors.</p><p><strong>Conclusion: </strong>These findings demonstrated the ameliorative potential of lycopene in acrylamide-induced reproductive toxicity by improving testicular antioxidant status, hormonal balance, spermatogenesis, and testicular androgen receptor expression in male Wistar rats.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052350","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":"Network toxicology and bioinformatics reveal potential molecular links between cadmium exposure and pancreatic cancer.","authors":"Shuyuan Liu, Xinyan Lu, Desheng Li, Jingyuan Ma, Yunshu Zhang, Junchen Li, Xing Wan, Dong Shang, Qingkai Zhang","doi":"10.1186/s40360-026-01156-6","DOIUrl":"10.1186/s40360-026-01156-6","url":null,"abstract":"<p><strong>Background: </strong>Environmental cadmium (Cd) pollution poses a severe threat to human health due to its strong bioaccumulation and high carcinogenicity. Although Cd exposure has been linked to various cancers, its specific role in pancreatic cancer (PC) remains unclear. This study aimed to explore the molecular mechanisms underlying Cd-associated PC and identify potential diagnostic and therapeutic targets.</p><p><strong>Methods: </strong>Transcriptomic data of PC were obtained from the GEO database to screen differentially expressed genes (DEGs), which were then intersected with Cd-related genes retrieved from the Comparative Toxicogenomics Database (CTD). Functional enrichment analyses, including GO and KEGG, were conducted to identify key biological processes and pathways. Multiple machine learning algorithms were used to construct a diagnostic model and identify hub genes. Furthermore, molecular docking and molecular dynamics simulations were performed to evaluate drug-target interactions, and in vitro experiments were used to validate the effects of Cd exposure on PC cell proliferation and invasiveness.</p><p><strong>Results: </strong>A total of five key genes-FN1, COL5A1, AHR, COL3A1, and TIMP1-were identified as core regulators of Cd-associated PC. Functional analyses indicated that Cd primarily affects the extracellular matrix (ECM) metabolic and collagen remodeling pathways. Experimental results confirmed that Cd exposure significantly enhanced the proliferation and invasiveness of PC cells. Molecular docking and dynamics simulations revealed that the EGFR inhibitor dacomitinib exhibited favorable predicted binding affinity to FN1, suggesting its potential as a therapeutic agent.</p><p><strong>Conclusions: </strong>This study reveals that Cd may promote the malignant progression of PC by regulating ECM remodeling through key genes such as FN1. Dacomitinib shows promise as an FN1-associated therapy, offering new insights for the precise prevention and treatment of Cd-associated PC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052330","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":"A retrospective study of the efficacy and safety of rituximab biosimilar for the treatment of membranous nephropathy.","authors":"Yu-Zhen Zou, Xiao-Li Du, Shao-Hong Wang, Rui Dai, Ran Xiao, Biao Wang","doi":"10.1186/s40360-026-01155-7","DOIUrl":"10.1186/s40360-026-01155-7","url":null,"abstract":"<p><strong>Background: </strong>Rituximab (RTX) is a monoclonal antibody that targets CD20 and is recommended by the KDIGO guidelines as a first-line treatment for membranous nephropathy (MN). The RTX biosimilar (HLX01) was the first biosimilar licensed in China in 2019. However, its efficacy and safety for MN treatment remain unclear. This study aimed to evaluate the performance of the RTX biosimilar for MN in a real-world setting.</p><p><strong>Methods: </strong>In this study, the medical records of 201 MN inpatients treated with high-dose RTX biosimilar and followed up for one year from January 2020 to December 2022 at PUMCH were retrospectively collected. Efficacy was evaluated in accordance with the KDIGO guidelines. Adverse reactions recorded in medical records during or after infusion were collected.</p><p><strong>Results: </strong>During the one-year follow-up period, the overall remission rate of high-dose RTX biosimilar treatment for MN was 75.12% (151/201), with 53 patients achieving complete remission and 98 patients reaching partial remission. The median time to remission was 6 months. Among patients who achieved remission, the relapse rate was 7.95% (12/151), among whom 7 patients achieved remission again after readministration. The remission rate was 78.79% (52/66) for treatment-naïve patients and 73.33% (99/135) for treated patients (P = 0.401). Adverse events included pruritus, flushing, hypotension, fever, rash, oropharyngeal discomfort, chest distress, eyelid edema, nausea and vomiting, and nasal congestion or rhinorrhea, with an overall incidence of 30.85% (62/201).</p><p><strong>Conclusions: </strong>Rituximab biosimilar has acceptable efficacy and safety in patients with MN, and their outcomes are similar to those of innovator RTX products reported in the literature. Thus, it may be used as an alternative to the innovator RTX as a first-line treatment for MN.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052409","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":"Clinical efficacy analysis of secukinumab combined with calcipotriol cream in the treatment of moderate to severe psoriasis in elderly patients.","authors":"Ling Lin, Wei Li, Qian Li, Xinjing Gao, Jingxin Zeng, Xin Zhou, Weiyu Liu, Xuelian Zhong, Yunqing Yang, Xibao Zhang, Quan Luo","doi":"10.1186/s40360-026-01112-4","DOIUrl":"10.1186/s40360-026-01112-4","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic immune-mediated inflammatory skin disorder, with plaque psoriasis being the most common clinical subtype, especially in elderly patients. Conventional therapies often provide suboptimal outcomes, necessitating the exploration of novel treatment approaches. This study evaluates the clinical efficacy of combining Secukinumab with Calcipotriol Cream in elderly patients with moderate to severe psoriasis.</p><p><strong>Methods: </strong>A total of 160 elderly patients (≥ 65 years) with plaque psoriasis were retrospectively analyzed between January 2020 and December 2024. All patients received baseline therapy with oral acitretin and topical clobetasol. The observation group (n = 80) additionally received secukinumab and calcipotriol cream. The control group (n = 80) received baseline therapy only. The primary endpoint was overall clinical efficacy based on Psoriasis Area and Severity Index (PASI) improvement. Secondary endpoints included changes in PASI scores, Dermatology Life Quality Index (DLQI), skin barrier parameters (stratum corneum hydration and sebum content), and incidence of adverse events over 12 weeks.</p><p><strong>Results: </strong>The total efficacy rate was significantly higher in the observation group than in the control group (90.0% vs. 72.5%, χ² = 8.306, P = 0.040). PASI scores were significantly reduced in both groups, with a greater reduction observed in the observation group (16.12 ± 3.13 vs. 18.98 ± 3.92; P < 0.001). Improvements in stratum corneum hydration (54.08 ± 6.05 vs. 50.20 ± 5.74; P < 0.001) and sebum content (138.20 ± 12.39 vs. 129.72 ± 10.68; P < 0.001) were also greater in the observation group. DLQI scores improved more significantly in the observation group (7.82 ± 1.05 vs. 9.52 ± 1.38; P < 0.001). Adverse events were infrequent and comparable between groups (P = 0.168). Post hoc power analysis confirmed sufficient statistical power (> 80%) across all primary endpoints.</p><p><strong>Conclusions: </strong>This retrospective study suggests that secukinumab combined with calcipotriol cream improves clinical outcomes and quality of life with good tolerability in elderly patients with moderate to severe psoriasis, supporting its potential therapeutic utility.</p><p><strong>Clinical trial: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013296","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":"Effect of oral semaglutide on cardiometabolic risk factors in overweight and obese individuals with or without diabetes: a systematic review and meta-analysis.","authors":"Niloofar Seighali, Mohammad Sadra Gholami-Chahkand, Mandana Ebrahimzade, Farzin Tahmasbi Arashlow, Seyede Parmis Maroufi, Parnian Rahnama, Mohammad Hassan Matin, Alireza Khodayari Javazm, Pouya Ebrahimi, Khurram Nasir, Rosy Thachil, Tor Biering Sørensen, Kaveh Hosseini","doi":"10.1186/s40360-026-01149-5","DOIUrl":"10.1186/s40360-026-01149-5","url":null,"abstract":"<p><strong>Background: </strong>Obesity is linked to cardiometabolic risk, and semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising option for weight and metabolic control. This systematic review and meta-analysis evaluated the effects of oral semaglutide, compared with placebo, on cardiometabolic risk factors in overweight and obese adults with or without diabetes.</p><p><strong>Materials and methods: </strong>In this systematic review and meta-analysis, following PRISMA 2020 guidelines, PubMed, Embase, and Scopus were searched through 25 August 2025. Randomized controlled trials (RCT) with overweight and obese populations, with or without diabetes, were included. The treatment and control groups received oral semaglutide and placebo, respectively. Outcomes were cardiometabolic factors and adverse events at baseline and follow-up. We pooled data using a random-effects model to estimate changes in outcomes by reporting Estimated Treatment Difference (ETD) as mean difference. Subgroup analyses were conducted based on dosage and follow-up duration.</p><p><strong>Results: </strong>Thirteen RCTs involving 26,284 participants met the criteria (52% received semaglutide). Female ratio of the semaglutide group was 30.1% and for the placebo group weas 33.3%. Compared with placebo, semaglutide showed significant reductions in body weight (ETD - 2.85 kg; 95% CI [- 4.03 to - 1.66]; p < 0.001), BMI (ETD - 0.66 kg/m²; 95% CI [- 0.95 to - 0.36]; p < 0.001), waist circumference (ETD - 1.79 cm; 95% CI [- 2.63 to - 0.95]; p < 0.001), HbA1c (ETD - 0.94%; 95% CI [- 1.13 to - 0.76]; p < 0.001), fasting plasma glucose (ETD - 26.91 mg/dL; 95% CI [- 33.56 to - 20.26]; p < 0.001), systolic blood pressure (ETD - 2.71 mmHg; 95% CI [- 3.70 to - 1.72]; p < 0.001), and diastolic blood pressure (ETD - 0.77 mmHg; 95% CI [- 1.38 to - 0.17]; p = 0.01) over 6 months. Benefits were consistent across different follow-up durations and doses. Gastrointestinal symptoms remained the most common adverse events (OR for GI issues = 2.69; nausea = 3.13; vomiting = 6.25; all p < 0.001). Semaglutide also showed a protective effect on cardiovascular events (OR = 0.64; p = 0.006).</p><p><strong>Conclusion: </strong>Oral semaglutide demonstrates meaningful improvements in cardiometabolic outcomes and a favorable safety profile, supporting its use as a non-invasive therapy for obesity and related metabolic disorders.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980277","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":"Omega-3 fatty acids attenuate alterations in penile erectile response by enhancing sexual behavior, nitric oxide-mediated signaling, and penile antioxidant status in tamoxifen-exposed rats.","authors":"Adeyemi Fatai Odetayo, Moses Agbomhere Hamed, Michael Olabode Allen, Aishat Oladoyin Ojewale-Jimoh, Bashirat Blessing Adedeji, Victor Olukayode Ekundina, Kazeem Bidemi Okesina","doi":"10.1186/s40360-026-01146-8","DOIUrl":"10.1186/s40360-026-01146-8","url":null,"abstract":"<p><strong>Background: </strong>The major type of breast cancer in males is the estrogen receptor-positive breast cancer, and can be managed with antiestrogenic hormonal compounds that have been reported to impair sexual functions in males. The commonest of these antiestrogenic agents is tamoxifen (TAM), which has also been shown to impair erectile function. Omega-3 fatty acids (O3FA), on the other hand, are an antioxidant obtained from diets, and they possess fertility-enhancing properties. In light of these, we considered the effect of O3FA on TAM-induced alterations in penile erectile response in male Wistar rats.</p><p><strong>Method: </strong>Sixty (60) male Wistar rats were randomized into four oral treatment groups (15 animals/group): control, O3FA (300 mg/kg), TAM (0.4 mg/kg), and TAM+O3FA treatment group. Male rats were placed in transparent cages under dim light, paired with hormonally primed receptive females, and sexual behavior was assessed before biochemical analysis.</p><p><strong>Results: </strong>TAM significantly disrupted male penile erectile reflexes and motivation to mate and decreased dopamine with the concomitant increase in serotonin, monoamine oxidase, arginase, and phosphodiesterase-5. These events were accompanied by a significant decrease in nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). Also, TAM exposure altered antioxidant status (evidenced by a significant increase in penile MDA and decrease in Nrf2, SOD, CAT, GSH, and GPx), leading to penile inflammatory response (increased IL-1β, TnF-α, MPO, Nf-κb, XO, and UA) and caspase-3-mediated apoptosis. However, O3FA co-treatment attenuated TAM-induced alterations in penile erectile response and boosted the NO-mediated signaling and antioxidant status.</p><p><strong>Conclusion: </strong>Based on these results, TAM administration in healthy rats was associated with increased penile oxidative stress, while O3FA attenuated some of these changes.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970152","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":"Efficacy and safety of rimegepant for acute and preventive treatment of migraine: a systematic review and meta-analysis of randomized controlled trials.","authors":"Dina M Khodeer, Sally M Abdelmonem, Komla Mawunyo Dossouvi, Mai Adawi, Eman Hamza, Dina A Ali","doi":"10.1186/s40360-026-01140-0","DOIUrl":"10.1186/s40360-026-01140-0","url":null,"abstract":"<p><strong>Background: </strong>Migraine is a disabling neurological disorder with limited tolerability and cardiovascular limitations associated with traditional acute therapies such as triptans. Rimegepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, has emerged as a promising treatment option. This meta-analysis evaluated the efficacy and safety of a single 75 mg oral dose of rimegepant for acute preventive treatment of migraine.</p><p><strong>Methods: </strong>A systematic search of PubMed, Scopus, and Web of Science was conducted from inception to October 2025. Only randomized controlled trials (RCTs) evaluating oral rimegepant 75 mg for acute migraine in adults were included. Primary outcomes included pain freedom and pain relief at 2, 24, and 48 h. Secondary outcomes included freedom from associated migraine symptoms, return to normal function, rescue medication use, and adverse events. A random-effects model was applied for pooled analysis.</p><p><strong>Results: </strong>Nine RCTs involving 7,198 participants were included. Participants received a single 75 mg oral dose of rimegepant per migraine attack. Rimegepant demonstrated significantly greater 2-hour pain freedom compared with placebo (RR = 1.77; 95% CI: 1.5-2.1). Two-hour pain relief was similarly improved (RR = 1.35; 95% CI: 1.28-1.42). Safety outcomes were comparable to placebo, with no significant differences in total adverse events (RR = 1.10) or serious adverse events.</p><p><strong>Conclusion: </strong>A single 75 mg oral dose of rimegepant is an effective and well-tolerated therapeutic option for both acute and preventive migraine treatment, offering meaningful clinical improvement and a favorable safety profile. Its non-vasoconstrictive mechanism provides a valuable alternative for patients unable to use triptans or those who respond inadequately to existing therapies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970139","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":"Comparative pharmacokinetics for bioequivalence of pramipexole dihydrochloride extended-release tablets in fasting and fed Chinese healthy volunteers: a randomized, open-label, single-dose, crossover study.","authors":"Qian Chen, Hui-Qing Shi, Yi-Fang Chen, Wei Zhang, Lan Ye, Ya-Ming Li, Ting-Ting Hu","doi":"10.1186/s40360-026-01144-w","DOIUrl":"10.1186/s40360-026-01144-w","url":null,"abstract":"<p><strong>Background: </strong>We aimed to compare pharmacokinetic (PK) profiles and establish bioequivalence between generic and original pramipexole extended-release (ER) tablets in healthy Chinese volunteers under fasting and fed conditions.</p><p><strong>Methods: </strong>This investigation consisted of two randomized, open-label, single-dose, two-period, crossover studies. In the first period of each study, a single oral dose (0.375 mg) of the test or reference pramipexole ER tablets was randomly assigned (1:1) to healthy Chinese volunteers. The investigator collected blood samples before and after dosing for up to 72 h and assessed the safety profile. The central laboratory staff, unaware of the study procedures, determined the plasma pramipexole based on a validated LC-MS/MS method. Primary PK endpoints, including peak concentration (C_max) and the areas under the plasma concentration-time curve (AUC_0-t, AUC_0-∞), were calculated and presented as mean ± SD using non-compartmental analysis with geometric mean ratios (90% confidence intervals) between the two study products.</p><p><strong>Results: </strong>In the fasting study (n = 24), C_max, AUC_0-t, and AUC_0-∞ were 0.45 ± 0.12 ng/mL, 9.46 ± 2.70 h·ng/mL, and 9.75 ± 2.72 h·ng/mL, following a single dose of the test product. In the fed study (n = 24), PK profiles (C_max, AUC_0-t, and AUC_0-∞: 0.52 ± 0.11 ng/mL, 9.52 ± 2.01 h·ng/mL, and 9.82 ± 2.05 h·ng/mL) were not affected by a high-fat diet in participants with a single dose of the test product. The test and reference products had comparable PK profiles in the two studies. The 90% CI of the GMR in C_max, AUC_0-t, and AUC_0-∞ between the two products was within 80.0% - 125.0% for bioequivalence. There were no serious adverse events reported in the fasting and fed studies.</p><p><strong>Conclusion: </strong>Findings in comparative PK profiles suggested bioequivalence between the generic and original pramipexole ER tablets in healthy Chinese volunteers under fasting and fed conditions. Pramipexole ER tablets had a favorable safety profile.</p><p><strong>Clinical trial registration: </strong>This study was prospectively registered (Registration number: CTR20170248; Date of registration: February 28, 2016) in the Chinese Clinical Trial Registration Platform ( http://www.chinadrugtrials.org.cn ). This trial registry is recognized and regulated by the Chinese National Medical Products Administration (NMPA). This study was retrospectively registered on ClinicalTrials.gov (Registration Number: NCT07519278; Date of registration: April 2, 2026) in the US ( www.</p><p><strong>Clinicaltrials: </strong>gov ). The two PK studies were conducted between March 22, 2017, and June 13, 2017.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873237","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":"Comparison of the anti-inflammatory effects of esomeprazole and fexuprazan in lipopolysaccharide-stimulated RAW 264.7 macrophages.","authors":"Gi-Beom Ju, Seong Jun Kim, Daye Lee, Min Je Kim, Wan-Kyu Ko, Min Jai Cho, Seil Sohn","doi":"10.1186/s40360-026-01147-7","DOIUrl":"10.1186/s40360-026-01147-7","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to examine the anti-inflammatory effects of esomeprazole (ESO) and fexuprazan (FEXU) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and evaluated voltage-gated potassium channel 1.3 (Kv1.3) to infer the involved mechanism.</p><p><strong>Methods: </strong>The production of nitric oxide (NO) and the expression of pro-inflammatory mediators and Kv1.3, influenced by ESO and FEXU, were measured by means of a quantitative analysis of NO production and by a quantitative real-time polymerase chain reaction (qRT-PCR), respectively. In addition, we assessed the inhibitory effects of ESO and FEXU on the activation of the mitogen-activated protein kinase (MAPK) signaling pathway by examining the phosphorylation states of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, via a Western blot analysis. We also investigated the effects of ESO and FEXU on macrophage polarization by evaluating the expressions of inducible nitric oxide synthase (iNOS) and cluster of differentiation (CD) 206 through immunocytochemistry (ICC) staining.</p><p><strong>Results: </strong>The production of NO and the expression of pro-inflammatory mediators, as well as Kv1.3, were reduced by both ESO and FEXU. FEXU showed a greater inhibitory effect for pro-inflammatory mediators and Kv1.3. Both agents were found to suppress the activation of the MAPK signaling pathway, with FEXU reducing JNK and p38 phosphorylation and ESO reducing p38 phosphorylation. FEXU led to reduced iNOS expression with a consequent increase in CD206. In contrast, ESO did not induce significant changes in iNOS and CD206 expression levels.</p><p><strong>Conclusion: </strong>These results suggest that FEXU has a superior anti-inflammatory effect relative to that of ESO, indicating its potential as an anti-inflammatory agent.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863492","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}