Pharmaceuticals最新文献

{"title":"White Grape Skin Extraction, Analytical Profile, and Biological Activity: From the Laboratory to the Industrial Scale Within a Circular Economy Framework.","authors":"Larissa Della Vedova, Giovanna Baron, Paolo Morazzoni, Sandro Santinello, Safwa Moheb El Haddad, Jose Antonio Valdés-González, Stefano Piazza, Mario Dell'Agli, Giancarlo Aldini, Francesca Gado","doi":"10.3390/ph18091373","DOIUrl":"10.3390/ph18091373","url":null,"abstract":"<p><p><b>Background:</b> The sustainable use of agro-industrial by-products is essential to reduce environmental impact and enhance resource efficiency. In this study, white grape skins (WGSs), a distillation by-product of grappa production, are valorized through the development of an eco-friendly extraction process. <b>Methods:</b> At the laboratory scale, water-based and hydroalcoholic extractions are evaluated, prioritizing the water-based method due to its better scalability and eco-sustainability. Furthermore, this green extraction method enables industrial scale-up by Distillerie Bonollo Umberto S.p.A. (Mestrino, Italy), resulting in Vituva^®, an industrial extract with a composition comparable to its water-based laboratory counterpart. LC-HRMS-based targeted metabolomics identified 50 metabolites in the hydroalcoholic extract, 36 in the water-based extract, and 37 in the industrial extract, which included mainly polyphenols such as flavonoids and phenolic acids. <b>Results:</b> In vitro assays show that the water-based and industrial extracts exhibit significant anti-inflammatory activity, especially in gastric epithelial cells, while the hydroalcoholic extract displays stronger antioxidant activity via Nrf2 pathway activation but was more cytotoxic, possibly due to polyphenol-induced hormesis. Notably, the industrial extract also activates Nrf2 to a lesser extent, supporting its dual bioactivity profile. Chemoinformatic and statistical analyses support the identification of the likely mechanisms of action. <b>Conclusions:</b> Overall, this work demonstrates how green chemistry and circular economy principles transform a waste product into a high-value bioactive ingredient.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177689","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":"Advances in Modeling the Inner Blood-Retinal Barrier: From Static Tissue Cell Cultures to Microphysiological Systems.","authors":"Aikaterini Apostolidi, Georgios Stergiopoulos, Sofia Bellou, Maria Markou, Theodore Fotsis, Carol Murphy, Eleni Bagli","doi":"10.3390/ph18091374","DOIUrl":"10.3390/ph18091374","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The inner blood-retinal barrier (iBRB) is a specialized neurovascular interface essential for retinal homeostasis and visual function and is compromised in several vision-threating conditions. Therefore, the ability to model iBRB function and dysfunction in a controlled, reproducible and scalable manner is crucial for pharmaceutical research. However, the complex anatomy and physiology of the iBRB raise challenges for cell-based in vitro modeling. <b>Methods/Results</b>: This review follows the evolution of iBRB models-from simple monolayers of retinal endothelial cells (ECs) to sophisticated multicellular microphysiological systems (MPs). Advanced diverse microfluidic platforms aim to replicate key structural, biochemical and functional aspects of the iBRB, each incorporating distinct strategies regarding cell sourcing, device design, flow dynamics and functional readouts. <b>Conclusions</b>: Despite their limitations, these models are highly valuable for drug screening and mechanistic studies aimed at preserving or restoring barrier integrity while also helping to bridge the translational gap in ophthalmic drug discovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177593","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":"Drugs Versus Microbiota: How Pharmacotherapy Affects Gut and Probiotic Bacteria.","authors":"Anna Zawistowska-Rojek, Stefan Tyski","doi":"10.3390/ph18091372","DOIUrl":"10.3390/ph18091372","url":null,"abstract":"<p><p>The gut microbiota plays a key role in digestion, nutrient absorption, immune system regulation and metabolite production, significantly impacting human health. The balance of the gut microbiota can be easily disturbed by external factors such as lifestyle, diet and drugs. Some medications-such as metformin used to treat type 2 diabetes, levothyroxine for hypothyroidism, statins for cardiovascular diseases, proton pump inhibitors for reducing stomach acid secretion, and pharmaceuticals for lowering blood pressure-can affect the balance of the gut microbiota, causing dysbiosis, which in turn may lead to other diseases. Dietary supplements, probiotics, prebiotics and certain medications alter the composition of the gut microbiota, which plays an essential role in alleviating metabolic disorders. This study discusses the effects of the long-term use of selected pharmaceuticals on the gut and probiotic microbiota in patients. It also examines whether there is a rationale for providing probiotic supplements.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177768","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":"Preparation and Application of Shen Ling Cao Composite Particles with Different Structures Based on Co-Spray Drying.","authors":"Zhe Li, Caiyun Sun, Ping Sun, Lingyu Yang, Qi Yang, Weifeng Zhu, Yongmei Guan, Wenjun Liu, Liangshan Ming","doi":"10.3390/ph18091369","DOIUrl":"10.3390/ph18091369","url":null,"abstract":"<p><p><b>Objectives:</b> Sen Ling Cao (SLC) is an excellent health food that has health-promoting functions, such as alleviating physical fatigue and boosting immune function. Currently, SLC is predominantly marketed and administered as an oral liquid, which suffers from the disadvantages of inconvenient transport and limited versatility. In this study, we investigated the preparation of direct compression (DC) tablets of SLC. <b>Methods:</b> Hydroxypropyl methylcellulose E3 (HPMC E3), polyvinylpyrrolidone K30 (PVP K30), hydroxypropyl cellulose EF (HPC EF), and maltodextrin (MD) were selected as modifying agents; and ammonium bicarbonate (NH₄HCO₃) and sodium bicarbonate (NaHCO₃) were employed as pore-forming agents. Co-spray drying was utilized to prepare 13 kinds of composite particles with different structures. Subsequently, their physical properties and compacting parameters were characterized comprehensively. Finally, the various composite particles were directly compacted into tablets to study the respective effects on the properties of DC tablets. <b>Results:</b> The results demonstrated that (i) the SLC composite particles have been successfully produced by co-spray drying, and processing involves physical changes; (ii) the tensile strength (TS) values of PCP-SLC-HPMC-NH₄HCO₃, PCP-SLC-PVP-NaHCO₃, PCP-SLC-HPC-NaHCO₃, and PCP-SLC-HPMC-NaHCO₃ were 9.8, 7.2, 8.3, and 7.7 times higher than that of SLC; (iii) all the modifiers studied could improve the DC properties of problematic SLC to some degree, and the combination of HPMC and NH₄HCO₃ showed to be the best to markedly improve both the compactibility and flowability of SLC. <b>Conclusions:</b> Overall, the design of porous composite particles, composite particles, and porous composite particles in this study successfully produced qualified tablets with high SLC loadings via DC. These findings are favorable for promoting the development and application of natural botanical tablets through DC.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177359","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":"Association of <i>ABCG2</i> Polymorphisms with Methotrexate Efficacy and Toxicity in Saudi Rheumatoid Arthritis Patients.","authors":"Zeina W Sharawi, Lina A Alqurashi, Ahlam M Alharthi, Ibtisam M Jali, Maha H Jamal, Yasser Bawazir, Mohammad Mustafa, Sami M Bahlas, Hassan Daghasi, Talal S Alharthi, Dalal Sameer Al Shaer, Rania Magadmi","doi":"10.3390/ph18091365","DOIUrl":"10.3390/ph18091365","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Methotrexate (MTX) is currently the most widely used treatment for Rheumatoid Arthritis (RA) due to its demonstrated efficacy and well-known safety profile. However, the effectiveness and toxicity of MTX can vary among patients, partly due to genetic factors. Therefore, this study aimed to investigate the associations between the polymorphisms in the ABC subfamily G member 2 (<i>ABCG2</i>) gene and MTX effectiveness/toxicity in Saudi Arabia RA patients. <b>Methods</b>: The study is a retrospective, multicenter, case-control study that uses Sanger sequencing techniques for genotyping. <b>Results</b>: More than half of the patients (55.56%) were poor responders, with a slightly higher mean age. However, there was no significant difference between the two groups, not only in terms of age but also in other demographics and clinical factors. Regarding the rs2231137 polymorphism, the CC, CT, and TT genotype frequency were 91%, 7%, and 2%, respectively. The mutated variant (TT) was only observed in the positive rheumatoid factor group. Notably, none of these genotypes displayed any significant correlation with demographic characteristics, clinical features, or MTX efficacy/toxicity. <b>Conclusions</b>: This study is the first pharmacogenetic study of rs2231137 polymorphism in RA patients utilizing linear regression, revealing that rs2231137 polymorphism is not a predictor of either MTX efficacy or toxicity in RA patients. Therefore, more research is needed.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177288","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":"Nicotine Misuse and Treatment of Schizophrenia Exacerbations in Men: An Observational Study in Poland.","authors":"Jakub Grabowski, Leszek Bidzan, Aleksandra Brzozowska","doi":"10.3390/ph18091366","DOIUrl":"10.3390/ph18091366","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Prevalence of nicotine misuse among schizophrenia patients is significantly higher than in the general population and is estimated at 70-90%. Past studies have shown that nicotine misuse affects the course of the schizophrenic process in terms of frequency of hospitalizations, age of the first onset, social functioning, and pharmacotherapy, among others. This study aimed to examine associations between smoking and psychopathology, course of hospitalization, doses of administered antipsychotics, and severity of adverse events in men hospitalized for exacerbations of schizophrenia. <b>Methods</b>: Protocol procedures were performed in 81 men (40 smokers and 41 non-smokers) and included assessments with a structured interview, laboratory tests, the Positive and Negative Syndrome Scale (PANSS), Montgomery and Asberg Depression Rating Scale (MADRS), Fagerstrom Test for Nicotine Dependence (FTND), and extrapyramidal symptom scales. <b>Results</b>: In both groups, a comparable number of patients met the criteria for remission. However, in the pre-discharge period, non-smokers had more severe depressive symptoms measured by MADRS and PANSS than smokers, as well as more severe and more frequent extrapyramidal symptoms. In contrast to previous research, significantly higher doses of antipsychotics measured in chlorpromazine equivalent (CPZE) doses were administered in non-smokers than in smokers (881.1 versus 689.3, <i>p</i> = 0.0305). Non-smokers were also more likely to need high doses of medication (>1000 milligrams CPZE) than smokers (43.9% versus 20%, <i>p</i> = 0.0212). However, these associations lost statistical significance after adjustment for initial severity and treatment-related factors. Comparison of CPZEs in the context of metabolic pathways suggests that variations in doses are independent of metabolism by cytochrome P450 1A2 (CYP1A2). The results also indicate that nicotine may help to differentiate between negative and depressive symptoms. <b>Conclusions</b>: In this male inpatient sample, smokers showed lower depressive symptom scores. Although smoking may affect some symptoms of schizophrenia according to the self-medication hypothesis, therapeutic measures aimed at smoking cessation should not be delayed in this group of patients.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177753","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":"Oligomeric Proanthocyanidins Reverse Lenvatinib Resistance in Hepatocellular Carcinoma Through ITGA3-Mediated Pathway.","authors":"Takayuki Noma, Yuan Li, Yuma Wada, Yuji Morine, Tetsuya Ikemoto, Yu Saito, Shinichiro Yamada, Hiroki Teraoku, Mitsuo Shimada, Ajay Goel","doi":"10.3390/ph18091361","DOIUrl":"10.3390/ph18091361","url":null,"abstract":"<p><p><b>Background</b>: Oligomeric proanthocyanidins (OPCs) are natural polyphenolic compounds with strong antitumor properties and have gained attention as potential agents to overcome drug resistance. Hepatocellular carcinoma (HCC) remains a major cause of cancer deaths worldwide, and although Lenvatinib is widely used, its effectiveness is limited by acquired resistance. This study explores the potential of OPCs to overcome Lenvatinib resistance in HCC. <b>Methods</b>: To evaluate the potential of OPCs to overcome Lenvatinib resistance in HCC, we established Lenvatinib-resistant Huh-7 and PLC-PRF-5 cell lines and conducted systematic cell culture experiments to assess their antitumor effects. Furthermore, genome-wide transcriptomic profiling, network pharmacology approaches, and pathway enrichment analysis were performed to identify resistance-associated signaling pathways that could serve as therapeutic targets. <b>Results</b>: The combination of OPCs and Lenvatinib demonstrated a significant synergistic anti-proliferative effect in resistant hepatocellular carcinoma cells, with the most synergistic dose combinations showing Bliss synergy scores exceeding 10. Transcriptomic profiling revealed that the adhesion molecule ITGA3 is a key factor in Lenvatinib resistance and contributes to the acquisition of anoikis resistance. The combination treatment suppressed ITGA3-EGFR-AKT signaling, restored anoikis sensitivity, significantly reduced spheroid formation (fold change = 0.10-0.12; <i>p</i> < 0.001), and markedly increased apoptosis (fold change = 2.7-5.0; <i>p</i> < 0.001). <b>Conclusions</b>: This study is the first to demonstrate that OPCs can overcome chemotherapy resistance by targeting the integrin pathway, providing scientific evidence for their potential use as an adjunctive therapy for chemotherapy-resistant HCC.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177688","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":"Progress of ERK Pathway-Modulated Natural Products for Anti-Non-Small-Cell Lung Cancer Activity.","authors":"Lin Xing, Chi Zhang, Jieying Yuan, Kai Zhu, Helena Tomás, Ruilong Sheng, Xiuwei H Yang, Qidong Tu, Ruihua Guo","doi":"10.3390/ph18091371","DOIUrl":"10.3390/ph18091371","url":null,"abstract":"<p><p>In recent decades, there has been a significant increase in new lung cancer cases and deaths globally, especially in China, which hindered the extension of human life expectancy and severely threatened public health. Natural products are important and sustainable sources of new anticancer drug molecules, offering new bioactive molecules with various structures and biofunctions for new anticancer drug development, which accounted for 40% of all anticancer drugs. Natural-based compounds could inhibit cancer cell proliferation and migration through a variety of anticancer mechanisms by the modulation/regulation of multiple biotargets and cell signaling pathways. In this review, we summarized the anticancer activities of flavonoids, terpenoids, glycosides, alcohols, coumarins, saccharides, and other natural compounds that could modulate the ERK-related signaling pathway in non-small-cell lung cancer (NSCLC) cells. We further elucidated the mechanistic pathways of natural compound combinations and computationally predicted their molecular docking affinities with ERK1/ERK2 protein targets, as well as providing an outlook on current studies, with the expectation that natural compounds will play more significant roles in future antitumor chemotherapy regimens.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177295","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":"Therapeutic Potential of Bioactive Compounds in Edible Mushroom-Derived Extracellular Vesicles: Isolation and Characterization of EVs from <i>Pleurotus eryngii</i>.","authors":"Gaia Cusumano, Agnese Bertoldi, Eleonora Calzoni, Husam B R Alabed, Roberto Maria Pellegrino, Lorena Urbanelli, Gokhan Zengin, Giancarlo Angeles Flores, Roberto Venanzoni, Paola Angelini, Carla Emiliani","doi":"10.3390/ph18091362","DOIUrl":"10.3390/ph18091362","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Over the past twenty years, there has been a rapid increase in studies aimed at comprehending how cells communicate with each other via Extracellular Vesicles (EVs), accompanied by a heightened interest in plant-derived extracellular vesicles due to their potential relevance in dietary supplementation and therapeutic applications. However, there is a limited amount of research on extracellular vesicles derived from mushrooms (MDEVs). Among edible mushrooms, <i>Pleurotus eryngii</i> is peculiar due to its flavor and interesting nutritional profiling. It also produces a wide array of secondary metabolites including biologically active compounds with many health-promoting benefits such as anticancer, antioxidant, antitumor, antiviral, antibacterial, antidiabetic, and anti-hypercholesteremic activities. The aim of this work has been to isolate EVs from the fruiting body and mycelium of <i>P. eryngii</i> in order to investigate their potential applications as nutraceuticals. <b>Methods</b>: MDEVs were isolated by differential and density gradient centrifugation, characterized by Nanoparticle Tracking Analysis (NTA), Scanning Electron Microscopy (SEM) and immunoblotting, and subjected to metabolomic and phenolic profiling. Their antioxidant potential was assessed through in vitro radical scavenging (DPPH, ABTS) and metal-reducing (CUPRAC, FRAP) assays. <b>Results</b>: The findings suggest that mycelium-derived EVs may represent a valuable source of high-quality MDEVs, which exhibited promising antioxidant properties in all assays conducted, particularly in radical scavenging assays. <b>Conclusions</b>: These results highlight the potential of <i>P. eryngii</i> mycelium-derived EVs as a novel natural source of bioactive compounds, paving the way for future applications in nutraceutical and therapeutic fields.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177309","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 Submaximal Doses of Semaglutide in Patients with Obesity on Metabolic Profile and Serum Levels of Adipocytokines.","authors":"Martin Jozef Péč, Jakub Jurica, Monika Péčová, Norbert Nagy, Boris Focko, Zuzana Miertová, Nikola Ferencová, Ivana Ságová, Ingrid Tonhajzerová, Tomáš Bolek, Peter Galajda, Marián Mokáň, Matej Samoš","doi":"10.3390/ph18091364","DOIUrl":"10.3390/ph18091364","url":null,"abstract":"<p><p><b>Background:</b> Obesity is closely linked to metabolic dysfunction and systemic low-grade inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized for obesity treatment due to their significant metabolic benefits, including weight loss and improved glycemic control. The aim of the study was to evaluate the effect of submaximal doses of long-lasting GLP-1RA semaglutide on selected biomarkers of obesity-related inflammation, adipocytokines levels and metabolism in a real-world population of obese patients. <b>Methods:</b> We performed a prospective, observational study involving 32 adult patients (11 men, 21 women; mean age 49 ± 12 years; BMI 40.5 ± 7.3 kg/m²) treated with submaximal doses of semaglutide over 12 weeks, together with hypocaloric diet and increased physical activity based. We analyzed selected biomarkers including insulin, leptin, ferritin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) before and after three months of treatment. <b>Results:</b> We observed significant reductions in weight, BMI, waist circumference, insulin and leptin levels (all <i>p</i> < 0.001). On the other hand, no significant changes were recorded in ferritin (<i>p</i> = 0.806), IL-6 (<i>p</i> = 0.607), TNF-α (<i>p</i> = 0.633), resistin (<i>p</i> = 0.250) or PAI-1 (<i>p</i> = 0.134) levels. Correlation analyses revealed the correlation between IL-6 and adiposity indices (BMI, waist circumference) both before and after treatment. Ferritin and PAI-1 levels positively correlated with waist circumference, while resistin showed a negative correlation with central obesity. <b>Conclusions:</b> Submaximal-dose GLP-1 RA therapy was associated with significant improvements in metabolic parameters and adipokine regulation, but did not affect systemic inflammatory markers within 12 weeks. Future studies with larger cohorts and longer follow-ups are needed to clarify the associations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177371","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}