Pharmaceuticals最新文献

{"title":"Ameliorative Effects of <i>Prunella vulgaris</i> on Lower Urinary Tract Symptoms Induced by Benign Prostatic Hyperplasia in SD Rats via Nitric Oxide and Potassium Channels.","authors":"Beno Ramesh Nirujan, Jeongsook Kim, Eun-Bok Baek, Kyungmi Kim, Nishani Jayanika Jayathilake, Youn Gil Kwak, Mi Ran Jang, Hyo Seong Ji, Hyo-Jung Kwun, Kyu Pil Lee","doi":"10.3390/ph18030400","DOIUrl":"10.3390/ph18030400","url":null,"abstract":"<p><p><b>Background:</b> Lower urinary tract symptoms (LUTS) due to prostate hyperplasia are the most frequent urological symptoms in elderly men. Current pharmacological treatments for LUTS and benign prostatic hyperplasia (BPH) are widely used in clinical practice; however, adverse effects associated with these drugs have been reported for sexual dysfunction and orthostatic hypotension. <i>Prunella vulgaris</i> (PV) is a medicinal herb that has a long history of use. This study aimed to address this gap by investigating the relaxant activity of PV extract (PVE) on rat prostate smooth muscle ex vivo and evaluating intravesical cystometry for its potential. <b>Methods and Results:</b> Ten male Sprague Dawley (SD) rats were used to study the relaxant efficacy of PVE and its constituents in isometric contraction ex vivo. Thirty-six SD rats were randomly assigned to six groups of six animals (n = 6) and administered testosterone propionate (TP; 3 mg/kg) daily for 4 weeks to induce BPH. Groups of BPH rats were treated with or without PVE (30, 60, or 90 mg/kg) via oral gavage. At the end of the experiments, the animals were subjected to intravesical pressure under urethane anesthesia. After successful cystometric recording, rats were euthanized with carbon dioxide. Prostate and bladder tissues were harvested and processed for histological and biochemical analysis. The results demonstrated that PVE exerted relaxant effects on prostatic smooth muscle in a concentration-dependent manner, mediated by nitric oxide and potassium channels, without antagonizing adrenergic receptors. Additionally, intravesical cystometry in SD rats treated with oral gavage of PVE for 4 weeks showed a significant improvement in voiding abnormalities. <b>Conclusions:</b> These findings suggest the potential of PV and its compounds as a therapeutic strategy to improve LUTS associated with BPH.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721065","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":"Puerarin Targets HIF-1α to Modulate Hypoxia-Related Sphingolipid Metabolism in Diabetic Hepatopathy via the SPTLC2/Ceramide Pathway.","authors":"Mangui Cai, Wenxi Lai, Huien Chen, Dongmin Cao, Boyan Zhang, Feng Wang, Minghua Xian, Shumei Wang","doi":"10.3390/ph18030398","DOIUrl":"10.3390/ph18030398","url":null,"abstract":"<p><p><b>Background and Objectives</b>: Diabetic hepatopathy, characterized by hepatic hypoxia and metabolic dysregulation, has a rising global incidence and prevalence, with limited effective treatments. Hepatic hypoxia activates hypoxia-inducible factor-1 alpha (HIF-1α), regulating sphingolipid metabolism and elevating ceramide, a key factor in insulin resistance. Puerarin (Pue), a flavonoid derived from Pueraria lobata, exhibits therapeutic effects in diabetes, but its effects on hypoxia-related hepatic metabolism are unclear. This study investigates Pue's mechanisms in modulating hepatic metabolism, focusing on HIF-1α and sphingolipid metabolism. <b>Methods</b>: Using bioinformatics and molecular docking, HIF-1α was identified as a key target in diabetic liver disease, confirmed via drug affinity responsive target stability. In vitro experiments utilized insulin-resistant HepG2 cells to assess glucose intake and HIF-1α expression. In vivo, type 2 diabetes mellitus (T2DM) was induced in mice using a high-fat diet and streptozotocin injections. Pue administration was evaluated for its effects on fasting blood glucose, oral glucose tolerance, and hepatoprotective effects. Liver metabolomics and qPCR/Western blot analyses were conducted to assess metabolic pathways. <b>Results</b>: Pue increased glucose uptake in HepG2 cells and bound HIF-1α. Pue reduced HIF-1α expression in HepG2 cells, an effect attenuated by the HIF-1α stabilizer DMOG. Pue improved fasting blood glucose, oral glucose tolerance, and hepatoprotective effects in T2DM mice, which DMOG reversed. Metabolomics revealed that Pue modulates sphingolipid metabolism, decreasing ceramide content. qPCR and Western blot results confirmed that Pue dramatically decreases HIF-1α and SPTLC2 expression. <b>Conclusions</b>: Pue improves diabetic hepatopathy by reducing ceramide expression through the HIF-1α/SPTLC2 pathway, offering a novel therapeutic strategy for diabetes management.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720623","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":"Synthesis, Cytotoxic and Genotoxic Evaluation of Drug-Loaded Silver Nanoparticles with Mebeverine and Its Analog.","authors":"Mihaela Stoyanova, Miglena Milusheva, Milena Georgieva, Penyo Ivanov, George Miloshev, Natalia Krasteva, Kamelia Hristova-Panusheva, Mehran Feizi-Dehnayebi, Ghodsi Mohammadi Ziarani, Kirila Stojnova, Slava Tsoneva, Mina Todorova, Stoyanka Nikolova","doi":"10.3390/ph18030397","DOIUrl":"10.3390/ph18030397","url":null,"abstract":"<p><p><b>Background:</b> Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with a complex pathogenesis that necessitates innovative therapeutic approaches for effective management. Among the commonly used treatments, mebeverine (MBH), an antispasmodic, is widely prescribed to alleviate IBS symptoms. However, challenges in delivering the drug precisely to the colonic region often hinder its therapeutic effectiveness. To address this limitation, silver nanoparticles (AgNPs) have emerged as promising drug delivery systems, offering unique physicochemical properties that can enhance the precision and efficacy of IBS treatments. <b>Objectives:</b> This study aimed to synthesize AgNPs as drug delivery vehicles for MBH and a previously reported analog. The research focused on evaluating the cytotoxic and genotoxic effects of the AgNPs and forecasting their possibly harmful effects on future sustainable development. <b>Methods:</b> AgNPs were synthesized using a rapid method and functionalized with MBH and its analog. The nanoparticles were characterized using different techniques. Cytotoxicity and genotoxicity were evaluated in vitro. Additionally, in silico docking analyses were performed to explore their safety profile further. <b>Results:</b> In vitro assays revealed concentration-dependent cytotoxic effects and a lack of genotoxic effects with MBH-loaded AgNPs. A molecular docking simulation was performed to confirm this effect. <b>Conclusions:</b> The study underscores the potential of AgNPs as advanced drug delivery systems for safe and significant therapeutic implications for IBS. Future in vivo and preclinical investigations are essential to validate the safe range of exposure doses and evaluation standards for assessing AgNPs' safety in targeted and personalized medicine.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721241","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":"Semaglutide as a GLP-1 Agonist: A Breakthrough in Obesity Treatment.","authors":"Rui Salvador, Carla Guimarães Moutinho, Carla Sousa, Ana Ferreira Vinha, Márcia Carvalho, Carla Matos","doi":"10.3390/ph18030399","DOIUrl":"10.3390/ph18030399","url":null,"abstract":"<p><p>This review addresses the role of semaglutide (SMG), a GLP-1 receptor agonist, in the treatment of obesity and its related comorbidities. Originally developed for type 2 diabetes (DM2), SMG has shown significant efficacy in weight reduction, with superior results compared to other treatments in the same class. Its effects include appetite suppression, increased satiety, and improvements in cardiovascular, renal, and metabolic parameters. Studies such as SUSTAIN, PIONEER, and STEP highlight its superiority compared to other GLP-1 receptor agonists and anti-obesity drugs. The oral formulation showed promising initial results, with higher doses (50 mg) showing weight losses comparable to those of subcutaneous administration. Despite its benefits, there are challenges, such as weight regain after cessation of treatment, gastrointestinal adverse effects, and variability of response. Future studies should explore strategies to mitigate these effects, identify predictive factors of efficacy, and expand therapeutic indications to other conditions related to obesity and insulin resistance. The constant innovation in this class of drugs reinforces the potential of SMG to transform treatment protocols for chronic weight-related diseases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721106","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":"Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody.","authors":"Yunqi Yao, Xiaoning Yang, Jing Li, Erhong Guo, Huiyu Wang, Chunyun Sun, Zhangyong Hong, Xiao Zhang, Jilei Jia, Rui Wang, Juan Ma, Yaqi Dai, Mingjing Deng, Chulin Yu, Lingling Sun, Liangzhi Xie","doi":"10.3390/ph18030395","DOIUrl":"10.3390/ph18030395","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Finotonlimab (SCTI10A) is a humanized anti-PD-1 antibody tested in Phase III trials for several solid tumor types. <b>Methods</b>: This study characterized the in vitro and in vivo efficacy, Fc-mediated effector function, and non-clinical PK/PD properties of finotonlimab. <b>Results</b>: The results demonstrated that finotonlimab is effective in stimulating human T cell function in vitro and exhibits marked antitumor efficacy in vivo using both PD-1-humanized and PBMC-reconstructed mouse models. Additionally, finotonlimab exhibited minimal impact on the activation of effector cells via Fc receptor-dependent pathways, potentially facilitating PD-1⁺ T cell killing. In cynomolgus monkeys, finotonlimab exhibited a nonlinear pharmacokinetic (PK) profile in a dose-dependent manner, and a receptor occupancy rate of approximately 90% was observed at 168 h following a single administration of 1 mg/kg. Finotonlimab's PK profile (especially C_max) was better than that of marketed antibodies. Following a 13-week successive administration of finotonlimab, a pharmacodynamic analysis revealed that a sustained mean receptor occupancy of PD-1 molecules on circulating T cells remained at or above 93% for up to 8 weeks, even at a dose of 3 mg/kg, and that there were higher antibody accumulations in different dose groups. <b>Conclusions</b>: Taken together, the preclinical findings are promising and provide the groundwork for evaluating the efficacy and pharmacodynamic characteristics of finotonlimab in clinical trials.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721167","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":"Expanding the Role of Heparin Derivatives in Oncology: From Anticoagulation to Antitumor Activity.","authors":"Jasmine Holail, Hatouf Husni Sukkarieh, Ahmad Aljada","doi":"10.3390/ph18030396","DOIUrl":"10.3390/ph18030396","url":null,"abstract":"<p><p>Current research demonstrates the expanding therapeutic potential of heparin derivatives in oncology, extending beyond traditional anticoagulation mechanisms. This systematic analysis examines the structural characteristics, molecular mechanisms, and therapeutic applications of heparin-based compounds in malignancy treatment. The essential antithrombin binding pentasaccharide sequence has enabled development of specialized molecular variants, particularly fractionated heparins and their non-anticoagulant counterparts. These agents exert antineoplastic effects via multiple pathways, particularly through modulation of heparanase enzymatic activity and specific protein-glycosaminoglycan interactions. Evidence from pivotal clinical trials (FRAGMATIC, MAGNOLIA, GASTRANOX) confirms efficacy in managing cancer-associated thrombosis while indicating potential enhancement of chemotherapeutic outcomes. The preparation methods utilize enzymatic cleavage reactions and selective chemical derivatization to generate structurally modified heparins exhibiting unique molecular characteristics and biological activities. Analysis of the glycosaminoglycan analog dociparstat sodium reveals significant activity in myeloid malignancies, mediated by specific interference with CXCL12/CXCR4 signaling cascades. Significant challenges remain in manufacturing scale-up, analytical validation, and long-term safety assessment. Future studies must address dose optimization, combination strategies, and controlled clinical trials to determine the full therapeutic potential of these compounds in clinical oncology.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721068","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":"Sulforaphane from Brassica Oleracea Induces Apoptosis in Oral Squamous Carcinoma Cells via p53 Activation and Mitochondrial Membrane Potential Dysfunction.","authors":"Pooja Narain Adtani, Sura Ali Ahmed Fuoad Al-Bayati, Walid Shaaban Elsayed","doi":"10.3390/ph18030393","DOIUrl":"10.3390/ph18030393","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Oral squamous cell carcinoma (OSCC) is a significant global health concern, necessitating the development of novel treatment strategies. The present study investigated the in vitro anticancer activity of sulforaphane (SFN), an isothiocyanate derived from Brassica oleracea, on the OECM-1 human oral squamous carcinoma cell line. <b>Methods:</b> OECM-1 cells were cultured and exposed to a range of SFN concentrations. To assess the cell viability and determine the half maximal inhibitory concentration (IC50) of SFN following 24 h of treatment, an MTT assay was performed. Apoptosis was evaluated using AO/PI staining, a TUNEL assay, Annexin V-FITC analysis, and a DNA fragmentation assay. Changes in the mitochondrial membrane potential were analyzed using a JC-1 staining assay. A Western blot assay was performed to assess the expression levels of apoptosis-associated proteins (Bax, Bcl2, caspase-3, caspase-9, PARP, Smad-4, p53, cytochrome c, and GAPDH). Cell cycle analysis was performed to validate the apoptotic findings. <b>Results:</b> The IC50 concentration of SFN was 5.7 µM. The apoptotic assays demonstrated an effective induction of apoptosis in the OECM-1 cells. Western blot analysis demonstrated the dose-dependent upregulation of p53, caspase-3, caspase-9, PARP, cytochrome c, and Bax and the downregulation of the anti-apoptotic proteins Bcl-2 and Smad-4 after SFN treatment. <b>Conclusions:</b> The data obtained indicate that SFN has significant potential to induce apoptosis in OECM-1 cells by disrupting mitochondrial function and modulating apoptotic pathways. The outcomes of our research indicate SFN's potential as a viable treatment drug for OSCC.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721198","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":"The Impact of Fentanyl and Morphine on Maternal Hemodynamics in Spinal Anesthesia for Cesarean Section.","authors":"Ramona Celia Moisa, Nicoleta Negrut, Iulia Codruta Macovei, Cezar Cristian Mihai Moisa, Harrie Toms John, Paula Marian","doi":"10.3390/ph18030392","DOIUrl":"10.3390/ph18030392","url":null,"abstract":"<p><p><b>Background:</b> Spinal anesthesia is considered the method of choice for elective cesarean sections; however, it is not without maternal-fetal risks. <b>Materials and Methods:</b> This study compared the effects on maternal hemodynamics of intrathecal administration of fentanyl or morphine in parturients undergoing spinal anesthesia with 0.5% hyperbaric bupivacaine, with doses varied between 7.5 and 11 mg, depending on the patient's height. Data from a cohort of 170 parturients were analyzed. The administered doses were intrathecal morphine at 0.1 mL (100 µg, solution of 1 mg/mL) or fentanyl at 0.25 mL (25 µg, solution of 50 µg/mL). This study included 80 patients in the fentanyl (F) group and 90 in the morphine (M) group. <b>Results:</b> Group F showed significantly higher post-intervention systolic blood pressure values than group M (95.30 ± 12.99 mmHg vs. 90.58 ± 14.75 mmHg, <i>p</i> = 0.032). The incidence of vomiting was significantly less frequent in group F compared to group M (1, 1.3% vs. 10, 11.1%, <i>p</i> = 0.011). The total dose of ephedrine required for hypotension correction was significantly lower in the F group (12.75 ± 13.26 mg vs. 17.72 ± 16.73 mg, <i>p</i> = 0.035). <b>Conclusions:</b> The addition of fentanyl as an adjuvant alongside the local anesthetic in cesarean section is associated with enhanced hemodynamic stability compared to morphine, requiring lower doses of ephedrine and contributing to increased patient safety during elective cesarean surgery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721188","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":"Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase.","authors":"Sunny Park, Min Kyu Kim, Sung Bin Park, Dong Hyeok Kim, Young Joo Byun, Soo An Choi","doi":"10.3390/ph18030394","DOIUrl":"10.3390/ph18030394","url":null,"abstract":"<p><p><b>Background:</b> Janus kinase (JAK) inhibitors are a new class of targeted therapies that block cytokines and the signal transduction and activators of transcription (STAT) pathway. However, post-marketing surveillance studies have led to revised recommendations, highlighting potential serious heart-related events and cancer risk of JAK inhibitors. Here, we aimed to determine the neurological adverse events (AEs) of JAK inhibitors (tofacitinib, ruxolitinib, and baricitinib) based on a global real-world database. <b>Methods:</b> We analyzed individual case safety reports from the Uppsala Monitoring Center from January 1968 to 4 April 2022. A disproportionality analysis was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) to detect signals. Signals were classified according to the hierarchy of the Medical Dictionary for Regulatory Activities (MedDRA). Additionally, a stratified disproportionality analysis by age group and sex was performed for major AEs. <b>Results:</b> A total of 30,051,159 reports for all drugs were analyzed in this study. Among 105,798 reports of tofacitinib, 14.1% (14,863 reports) were neurological AEs. For ruxolitinib and baricitinib, 14.5% (6317 reports) and 10.2% (1216 reports) were neurological AEs, respectively. Various neurological AE signals were detected for tofacitinib and ruxolitinib, with memory impairment exhibiting the highest number of reports and a positive signal in the stratified disproportionality analysis by age group. Baricitinib did not reach the signal detection threshold. <b>Conclusions:</b> This study suggests the potential for neurological AEs, including memory impairment, associated with tofacitinib and ruxolitinib use based on a real-world database.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721197","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":"Oxytocin Protects PC12 Cells Against β-Amyloid-Induced Cell Injury.","authors":"Mohammed Mufadhe Alanazi, Awatif B Albaker, Lamia A Alzaagi, Jawza F Alsabhan, Fawaz Alasmari, Mohammed M Almutairi, Metab S Alharbi, Abdullah F Alasmari, Faleh Alqahtani, Sary Alsanea","doi":"10.3390/ph18030390","DOIUrl":"10.3390/ph18030390","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Neurodegenerative diseases, particularly Alzheimer's disease (AD), are characterized by progressive cognitive decline and non-cognitive symptoms that significantly affect health and quality of life. Beta-amyloid (Aβ) protein accumulation is a key factor in AD pathology, leading to neuronal damage. Oxytocin (OXT), a neuropeptide with neuroprotective potential, has garnered interest owing to its ability to mitigate neurotoxicity. We hypothesized that oxytocin could protect PC12 cells from Aβ-induced cytotoxicity through antioxidant effects and modulation of apoptotic pathways (i.e., mitochondrial and MAPK pathways). In this study, we aim to assess oxytocin's protective effects on cell viability, oxidative stress, mitochondrial function, and apoptotic signaling. <b>Methods</b>: PC12 cells were treated with Aβ25-35 and pre-treated with varying oxytocin concentrations to assess cell viability, reactive oxygen species (ROS) generation, and mitochondrial membrane potential. Western blotting was performed to analyze the effects on mitochondrial apoptosis and MAPK pathways. <b>Results</b>: Oxytocin treatment significantly improved cell viability in a dose-dependent manner and reduced Aβ-induced oxidative stress and mitochondrial dysfunction. Oxytocin-treated groups exhibited decreased ROS levels, increased mitochondrial membrane potential, and modulation of apoptosis-related proteins. Oxytocin upregulated phosphorylated ERK1/2 and Bcl-2 while downregulating BAX and caspase-3, reducing the BAX/Bcl-2 ratio. <b>Conclusions</b>: Oxytocin effectively protects PC12 cells from Aβ-induced neurotoxicity, highlighting its potential as a therapeutic agent for AD. Further research is needed to clarify oxytocin's mechanisms and clinical implications in AD treatment.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721221","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}