Pharmacological Reports最新文献

{"title":"Recent advances in indole-thiazole hybrid scaffolds: synthesis, molecular hybridization, and pharmacological potential.","authors":"Doaa A Abdelrheem, Sally Mostafa Khadrawy, Mohamed A M Ali, Saleh Alkhedhairi, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi, Emadeldin M Kamel","doi":"10.1007/s43440-026-00856-4","DOIUrl":"https://doi.org/10.1007/s43440-026-00856-4","url":null,"abstract":"<p><p>Indole-thiazole hybrids have attracted increasing interest in medicinal chemistry in recent years, combining the privileged indole nucleus with the thiazole ring within a single framework. The indole unit offers opportunities for π-π interactions and hydrogen bonding, while the thiazole ring enables tuning of lipophilicity and electronic properties and can support additional heteroatom-mediated interactions. This review summarizes synthetic approaches, structure-activity relationships (SAR), computational studies, and reported biological activities of indole-thiazole hybrids. The discussed applications include anticancer and antimicrobial studies, antidiabetic activity, and selected enzyme inhibition. Emerging directions such as greener multicomponent routes, structure-based design and docking, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation are highlighted. Finally, key challenges and perspectives for optimizing indole-thiazole hybrids as therapeutic leads are outlined.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841398","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":"Unraveling the therapeutic potential of luteolin in renal pathology: a comprehensive pathway oriented approach.","authors":"Lovedeep Singh, Anish Singh, Ayush Kattna, Diksha Dalal","doi":"10.1007/s43440-026-00858-2","DOIUrl":"https://doi.org/10.1007/s43440-026-00858-2","url":null,"abstract":"<p><p>Kidney diseases, particularly chronic kidney disease (CKD), represent a significant global health challenge, affecting over 9.5% of the world's population. Both systemic inflammation and oxidative stress are strongly associated with the development of CKD and contribute to the emergence of numerous complications. Renal injury is driven by interconnected molecular pathways that collectively exacerbate inflammation, oxidative stress, and fibrotic responses. The activation of mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling cascades, along with NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly, synergistically amplifies the inflammatory response. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) promotes excessive generation of reactive oxygen species (ROS), whereas impairment of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling weakens antioxidant defenses; together, these mechanisms exacerbate oxidative stress. In addition to oxidative stress, hyperglycemia also exacerbates renal damage by activating the transforming growth factor-beta (TGF-β)/hypoxia-inducible factor-1 alpha (HIF-1α) signaling axis, thereby promoting renal fibrosis. Collectively, these events culminate in progressive renal dysfunction. In addition to conventional therapies involving anti-inflammatory and antioxidant agents, emerging studies highlight the therapeutic potential of plant-derived agents in mitigating these pathological disturbances. Luteolin is a naturally occurring flavonoid abundantly distributed in a variety of dietary and medicinal plants, such as parsley, celery, green pepper, and carrots. It is predominantly found in members of the Lamiaceae, Asteraceae, Apiaceae, Fabaceae, and Poaceae families. Several studies highlight luteolin's potential in alleviating renal diseases by targeting key mediators, including NF-κB, NLRP3, MAPK, NOX4, ROS, SIRT1, TGF-β, cytokines, and antioxidants, among others. Thus, considering the broad therapeutic potential of luteolin and the complex pathophysiology of renal diseases, the present study aims to elucidate the mechanisms through which luteolin mitigates renal injury.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841424","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":"The novel third-generation antipsychotic drug brexpiprazole affects hepatic transcription factors, serum hormone levels, and cytochrome P450 enzymes after prolonged treatment: pharmacological significance.","authors":"Przemysław J Danek, Renata Pukło, Władysława A Daniel","doi":"10.1007/s43440-026-00859-1","DOIUrl":"https://doi.org/10.1007/s43440-026-00859-1","url":null,"abstract":"<p><strong>Background: </strong>Brexpiprazole is a third-generation antipsychotic used for the treatment of schizophrenia or as an adjunctive drug for the treatment of affective and neurological disorders. The combined treatments with brexpiprazole and other drugs that are also cytochrome P450 (CYP) substrates may lead to pharmacokinetic drug-drug interactions. Our present work aimed to investigate the effects of prolonged administration of brexpiprazole on the expression of hepatic transcription factors and CYP drug-metabolizing enzymes.</p><p><strong>Methods: </strong>Male Wistar rats received brexpiprazole (1 mg/kg ip.) for two weeks. Their livers were excised 24 h after the last dose, and the activities (HPLC), protein levels (Western blotting), and mRNAs (qRT-PCR) of CYP enzymes were measured. In parallel, the expression of hepatic transcription factors (Western blotting, qRT-PCR) and the concentration of serum hormones (ELISA) were assessed.</p><p><strong>Results: </strong>Brexpiprazole produced a broad-spectrum effect on CYP expression and activity. It enhanced the expression and activity of CYP1A, CYP2A, CYP3A1/2, and the activity of CYP2B, but decreased the expression/activity of CYP2Ds and CYP2E1. The observed changes in CYP enzymes corresponded to alterations in transcription factors: the increased expression of PXR and AhR, and decreased expression of PPARγ, LXR, and FXR. The above modifications in CYP enzymes' expression were accompanied by enhanced corticosterone and reduced T₄ serum levels.</p><p><strong>Conclusions: </strong>Brexpiprazole affects the expression of hepatic transcription factors and CYP, which may impact its own biotransformation and the metabolism of endogenous substances and concomitantly administered drugs, and lead to drug-drug interactions of pharmacological/clinical importance.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841394","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":"Prospects and challenges in intracellular delivery of therapeutic proteins.","authors":"Zakia Sultana, Ashif Ahamed, Muddasarul Hoda, Safdar Ali, Mehboob Hoque","doi":"10.1007/s43440-026-00855-5","DOIUrl":"https://doi.org/10.1007/s43440-026-00855-5","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841345","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":"Redox rewiring in glioblastoma: the thioredoxin system as a precision therapeutic target.","authors":"Hilda Espinoza, Agustín Gómez-Barrientos, Francisco López-Godoy, Pablo J Tapia, Mariela Puebla","doi":"10.1007/s43440-026-00857-3","DOIUrl":"https://doi.org/10.1007/s43440-026-00857-3","url":null,"abstract":"<p><p>The thioredoxin system, comprising thioredoxin (Trx) and thioredoxin reductase (TrxR), is a central regulator of cellular redox homeostasis and plays essential roles in normal brain physiology and redox signaling. In glioblastoma (GBM), this system undergoes profound pathological rewiring, creating a redox dependency that represents a potential therapeutic vulnerability. The overexpression of Trx and TrxR in GBM promotes tumor proliferation, invasion, angiogenesis, and resistance to chemotherapy and radiotherapy, while the endogenous Trx inhibitor, thioredoxin-interacting protein (TXNIP), is frequently downregulated. This imbalance drives redox adaptation and sustains tumor survival under metabolic and therapeutic stress. Pharmacological modulation of the Trx system using synthetic inhibitors, such as auranofin, platinum-based compounds, and PX-12, as well as selected natural compounds including curcumin analogs and flavonoids, has shown efficacy in preclinical GBM models by inducing oxidative stress and enhancing sensitivity to standard therapies. Emerging evidence also suggests that Trx system targeting may modulate the tumor immune microenvironment, providing a rationale for combination strategies with immunomodulatory approaches. Overall, targeting the Trx system represents a promising precision oncology strategy for GBM. Future efforts should focus on the development of brain-penetrant inhibitors, rational combination therapies, and predictive biomarkers to facilitate clinical translation. Given the essential role of the Trx system in normal brain homeostasis, therapeutic targeting requires careful consideration of safety, therapeutic index, and tumor-selective vulnerabilities. This narrative review discusses current evidence on the physiological functions of the Trx system in the brain, its dysregulation in GBM, and its relevance as a precision therapeutic target.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A validated FACS-based protocol for the isolation of neuronal and non-neuronal cells from frozen adult brain, suitable for integrated gene and protein analysis.","authors":"Magdalena Kolasa, Adam Roman, Przemysław Mielczarek, Joanna Solich, Agata Faron-Górecka","doi":"10.1007/s43440-026-00854-6","DOIUrl":"https://doi.org/10.1007/s43440-026-00854-6","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778125","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":"Sigma receptor ligands in selected affective disorders, psychoses, and addictions - a narrative review.","authors":"Agnieszka Piechal, Alicja Jakimiuk, Justyna Pyrzanowska","doi":"10.1007/s43440-026-00852-8","DOIUrl":"https://doi.org/10.1007/s43440-026-00852-8","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628428","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":"Glutathione deficiency in the early postnatal developmental period as a neurodevelopmental animal model of schizophrenia.","authors":"Zofia Rogóż, Agnieszka Wąsik","doi":"10.1007/s43440-026-00853-7","DOIUrl":"https://doi.org/10.1007/s43440-026-00853-7","url":null,"abstract":"<p><p>The etiopathology of schizophrenia is still poorly understood. Still, it is widely accepted that oxidative stress, particularly during early stages of brain development, is associated with increased risk of developing schizophrenia. Several studies indicate that glutathione (GSH) is a key factor in maintaining redox balance in cells and is involved in numerous metabolic processes. Its deficiency in the neonatal period leads to permanent brain damage, manifested by schizophrenia-like symptoms in adults. Hence, administration of the GSH synthesis inhibitor L-buthionine-(S, R)-sulfoximine (BSO) alone and in co-treatment with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4-3-(3-phenylpropyl) (GBR 12909) to rodents in neonatal period produces good neurodevelopmental models offering an opportunity to examine various neuroanatomical changes and different symptoms in schizophrenia spectrum. Schizophrenia is modeled by inducing lesions or changes in activity in specific brain regions of rodents (primarily the prefrontal cortex and hippocampus). Such artificially induced dysfunctions, discussed in this article, suggest the usefulness of these neurodevelopmental models in research on the pathomechanisms of schizophrenia. The aim of this review is to analyze the literature on the impact of GSH deficiency on the etiopathology of schizophrenia, with particular emphasis on neurodevelopmental animal models in which oxidative stress during early postnatal development causes schizophrenia-like symptoms in adulthood.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628482","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":"Potential antidepressant properties of aminophylline in male mice exposed to chronic restraint stress.","authors":"Florence Ingred Samante, Christine Gale Galangue, Debbie Chenn Avelino, Antoneitte Joy Beltran, Michaela Rapada, Eldan Greg Pabia, Niel Andrew Bustamante, Chrislean Jun Botanas, Fred Lawrence Samante, Katrina Joy Bormate, Raly James Perez Custodio","doi":"10.1007/s43440-026-00851-9","DOIUrl":"https://doi.org/10.1007/s43440-026-00851-9","url":null,"abstract":"<p><strong>Background: </strong>Aminophylline, a bronchodilator used for treating airway obstruction, has been predicted through in silico models to exert antidepressant effects. However, there are still no studies that have validated these claims in a biological system. In this paper, we evaluated the antidepressant effects of aminophylline in mice subjected to chronic restraint stress (CRS).</p><p><strong>Methods: </strong>CRS was conducted for a duration of 15 days, with 4-hour daily stress exposure. Aminophylline (5 mg/kg, 10 mg/kg, and 20 mg/kg) and fluoxetine (10 mg/kg, positive control) were administered daily via intraperitoneal injection. Behavioral assessments, including the tail suspension test (TST), forced swimming test (FST), and sucrose splash test (SST), were conducted on days 0, 5, 10, and 15. Molecular docking and pathway analyses were performed to provide insight into its possible mechanism of action.</p><p><strong>Results: </strong>CRS exposure successfully induced depressive-like behavior, characterized by prolonged immobility in the TST and FST and diminished grooming activity in the SST. Administration of aminophylline attenuated these behavioral deficits, reducing immobility time and increasing grooming time in a dose-dependent manner. Molecular docking analysis demonstrated favorable binding of aminophylline to phosphodiesterase 3, phosphodiesterase 4, and the serotonin transporter, targets associated with antidepressant activity. Pathway analysis revealed upregulation of PPAR signaling, calcium signaling, and the synaptic vesicle cycle, while downregulating the glutamatergic synapse pathway.</p><p><strong>Conclusion: </strong>The study provides the first evidence of the antidepressant activity of aminophylline in a validated model of depression, prompting further clinical investigation into its therapeutic potential. Moreover, molecular and biochemical analyses are warranted to validate its precise mechanism of action.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary proof-of-concept trial on the effects of ketamine on fatigue: a randomized crossover trial.","authors":"Taichi Goto, Joy D Kreskow, Alexander L R Ross, Catherine L Blumhorst, Justin J Zhao, Andrew J Mannes, Miroslav Bačkonja, Carlos A Zarate, Leorey N Saligan","doi":"10.1007/s43440-025-00808-4","DOIUrl":"10.1007/s43440-025-00808-4","url":null,"abstract":"<p><strong>Background: </strong>Fatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed the anti-fatigue effects of ketamine (0.5 mg/kg) versus midazolam (0.045 mg/kg), the active comparator.</p><p><strong>Methods: </strong>Ten participants, who were cancer survivors, with fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, or systemic lupus erythematosus, were randomized into Arm 1 (n = 4, Period 1: ketamine to Period 2: midazolam) or Arm 2 (n = 6, Period 1: midazolam to Period 2: ketamine).</p><p><strong>Results: </strong>The two periods were separately analyzed because of carryover effects with baseline fatigue scores, assessed by the fatigue visual analog scale (VAS), between the study periods (p = 0.03). Looking at changes in fatigue VAS scores from baseline (pre-infusion) to 3 days post-infusion, the ketamine group had a 21.0% decrease in Period 1 and 10.9% in Period 2, while the midazolam group showed a 17.7% decrease in Period 1 and 12.6% in Period 2. We did not observe a statistically significant difference in both periods. The largest fatigue score reduction for the ketamine group was at 1 day post-infusion, at - 38.7% in Period 1.</p><p><strong>Conclusion: </strong>Despite no statistical significance, a reduction in real-time fatigue scores was observed, which exceeded the 20% efficacy threshold, the primary outcome, in the ketamine arm from pre-infusion to 3 days post-infusion. The carryover effects and the peak reduction in fatigue at 24 hours after ketamine administration suggest that future trials may need to consider a study design without cross-over and an optimal active placebo alternative.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"558-567"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019271","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}