Acta Pharmaceutica最新文献

Scutellarin mitigates LPS-ATP-induced cardiomyocyte pyroptosis through the inhibition of the NLRP3/caspase-1/GSDMD signalling pathway. 黄芩苷通过抑制NLRP3/caspase-1/GSDMD信号通路减轻lps - atp诱导的心肌细胞焦亡。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-16 DOI: 10.2478/acph-2025-0025

Xiao-Wei Li, Yun-Fei Chen, Lan Zhou, Peng Zhou, Peng Huang, Qian Niu, Jin-Cai Li

{"title":"Scutellarin mitigates LPS-ATP-induced cardiomyocyte pyroptosis through the inhibition of the NLRP3/caspase-1/GSDMD signalling pathway.","authors":"Xiao-Wei Li, Yun-Fei Chen, Lan Zhou, Peng Zhou, Peng Huang, Qian Niu, Jin-Cai Li","doi":"10.2478/acph-2025-0025","DOIUrl":"https://doi.org/10.2478/acph-2025-0025","url":null,"abstract":"Scutellarin has a good myocardial protective effect. However, the underlying mechanism of scutellarin on cardiomyocyte pyroptosis remains unclear. In this study, we elucidated the mechanism of scutellarin to protect the injured myocardium. The molecular docking technique was used to predict the targets of scutellarin in protecting against myocardial injury. H9c2 cell pyroptosis was induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Then, the activities of CK and LDH were measured through a colourimetric assay. The level of cTnI was quantified by ELISA. mRNA expressions of NLRP3, cysteine-dependent aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were analyzed using RT-qPCR. Protein expressions of NLRP3, caspase-1, and GSDMD were detected by the immunofluorescence technique. Protein expression of NLRP3 was analysed by using Western blotting. Scutellarin had a good binding affinity with NLRP3, caspase-1, and GSDMD. Compared with LSP and ATP-treated cells, concentrations of 25, 50, and 100 µmol L-1 scutellarin reduced CK and LDH activities and the level of cTnI, decreased the mRNA expression of NLRP3, caspase-1, and GSDMD. In the mechanism study, scutellarin decreased mRNA expressions of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18, and reduced the fluorescence expressions of NLRP3, caspase-1, and GSDMD. Scutellarin reduced the protein expression of NLRP3. Scutellarin inhibits myocardial cell pyroptosis induced by LPS and ATP, and the mechanism is related to the NLRP3/caspase-1/GSDMD signalling pathway.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances in the treatment of non-alcoholic fatty liver disease with astragaloside IV. 黄芪甲苷治疗非酒精性脂肪肝的最新进展。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-16 DOI: 10.2478/acph-2025-0022

Hui Wang, Yunqin Jiang, Shiyun Wang, Chanchan Lu, Lumin Tang, Tingting Gu, Shu Shu

{"title":"Recent advances in the treatment of non-alcoholic fatty liver disease with astragaloside IV.","authors":"Hui Wang, Yunqin Jiang, Shiyun Wang, Chanchan Lu, Lumin Tang, Tingting Gu, Shu Shu","doi":"10.2478/acph-2025-0022","DOIUrl":"https://doi.org/10.2478/acph-2025-0022","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has become a global health challenge. With the lack of effective FDA-approved treatments, alternative therapies are being explored. Astragaloside IV (AS-IV), a bio-active compound derived from the plant Astragalus membranaceus (Fisch. ex Bunge) (Fabaceae/Leguminosae), native to Inner Mongolia and Siberia, has shown significant therapeutic potential in NAFLD. This review discusses the pharmacological effects and molecular mechanisms of AS-IV, highlighting its role in improving insulin resistance, regulating lipid metabolism, reducing oxidative stress and modulating inflammation. AS-IV acts through key molecular pathways, such as AMPK, Nrf2 and SREBP-1c, to mitigate liver steatosis and inflammation. Additionally, AS-IV influences gut microbiota and bile acid metabolism, contributing to its therapeutic effects. Despite promising results from preclinical studies, clinical data supporting AS-IV's efficacy in NAFLD treatment are limited. Future research should focus on clinical trials, pharmacokinetics, and the combination of AS-IV with other therapeutic agents to optimise its therapeutic potential and reduce side effects.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of magnetic N-doped carbon dots as pH-responsive targeted molecule cargo and its antioxidant and antibacterial behaviour. 磁性n掺杂碳点作为ph响应靶向分子货物的合成及其抗氧化和抗菌性能。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-16 DOI: 10.2478/acph-2025-0017

Hayat Alzahrani, Mohammed S Alkaltham, Tawfiq Alsulami, Abdulhakeem Alzahrani, Suleiman A Althawab

{"title":"Synthesis of magnetic N-doped carbon dots as pH-responsive targeted molecule cargo and its antioxidant and antibacterial behaviour.","authors":"Hayat Alzahrani, Mohammed S Alkaltham, Tawfiq Alsulami, Abdulhakeem Alzahrani, Suleiman A Althawab","doi":"10.2478/acph-2025-0017","DOIUrl":"https://doi.org/10.2478/acph-2025-0017","url":null,"abstract":"This study successfully generated magnetic N-doped carbon dots (CDs-MNPs) that exhibit two distinct functions: pH-responsive targeted drug delivery and powerful antioxidant action. The structural integrity, magnetic characteristics, and thermal stability of the samples were confirmed using comprehensive characterisation techniques, such as scanning electron microscopy, superconducting quantum interference device, Fourier Transform Infrared Spectroscopy, X-ray diffraction, continuous-wave electron para-magnetic resonance, X-ray photoelectron spectroscopy, surface porosity and thermogravimetric analysis. The CDs-MNPs displayed pH-dependent drug release profiles that conformed to zero-order, Higuchi, and Peppas models, demonstrating their ability to provide regulated release. The antioxidant activity of the carbon dots was assessed using the DPPH assay, where the radical scavenging capacity exceeded 80 %. This high level of activity was attributed to the synergistic effects of nitrogen doping and the functional groups present on the carbon dots. The biocompatibility of the specimen (up to 100 mg mL-1), which is essential for biomedical applications, was confirmed by MTT assays. This study highlights the potential of CDs-MNPs as an effective option for therapeutic interventions, providing customised drug delivery and antioxidant advantages. The antibacterial activity of CDs-MNPs was evaluated against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacterial strains, demonstrating significant efficacy. These results highlight the potential of CD-based nanobactericides for applications in biomedical and food monitoring.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

α-Heteroarylthiomethyl ketones: Small molecule inhibitors of 3CL^pro. α-杂芳基硫甲基酮：3CLpro的小分子抑制剂。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0023

Damijan Knez, Matic Proj, Krištof Bozovičar, Stanislav Gobec

引用次数: 0

SARS-CoV-2 structural proteins affect the expression of IL-8 and TNF-α cytokines and APOBEC genes in human lung A549 and liver Huh-7 cells. SARS-CoV-2结构蛋白影响人肺A549和肝Huh-7细胞中IL-8、TNF-α细胞因子和APOBEC基因的表达

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0024

Martina Bergant Marušič, Margarida Costa, Špela Turk, Nika Lovšin

{"title":"SARS-CoV-2 structural proteins affect the expression of IL-8 and TNF-α cytokines and APOBEC genes in human lung A549 and liver Huh-7 cells.","authors":"Martina Bergant Marušič, Margarida Costa, Špela Turk, Nika Lovšin","doi":"10.2478/acph-2025-0024","DOIUrl":"10.2478/acph-2025-0024","url":null,"abstract":"The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of cytidine deami nases responsible for DNA and RNA sequence editing, playing pivotal roles in a wide range of biological processes, including immune responses, antiviral properties, and genetic mutations. In this work, we investigated the effect of SARS-CoV-2 structural proteins - Envelope (E), Spike (S), Nucleocapsid (N), Membrane (M) and protein ORF6 - on the expression of cytokines Interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α), and APOBEC3s proteins (APOBEC3B and APOBEC3F) genes in Huh-7 and A549 human cell lines. While there is plenty of scientific evidence about the effects of SARS-CoV-2 on the inflammatory cascade, the current literature regarding the impact of SARS-CoV-2 on APOBEC expression is scarce. Our findings reveal a complex relationship between SARS-CoV-2 structural proteins and the host immune response, as certain viral structural proteins (S, M, E) modulate cytokine expression, potentially contributing to the dysregulated immune responses seen in COVID-19 patients. Additionally, our research uncovered interactions between viral proteins and APOBEC genes. This study contributes to a better understanding of the host-virus interactions in the context of SARS-CoV-2 infection and provides some insights into potential therapeutic targets for mitigating the immunopathological consequences of the disease.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"299-307"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical characteristics of the 6-nitro regioisomer of nitroxoline and its 1,2,3,4-tetrahydroquinoline analogues. 硝基喹啉及其1,2,3,4-四氢喹啉类似物6-硝基区域异构体的生化特性

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0018

Ana Mitrović, Damijan Knez, Martina Hrast Rambaher, Jakob Kljun, Janko Kos, Stanislav Gobec, Izidor Sosič

{"title":"Biochemical characteristics of the 6-nitro regioisomer of nitroxoline and its 1,2,3,4-tetrahydroquinoline analogues.","authors":"Ana Mitrović, Damijan Knez, Martina Hrast Rambaher, Jakob Kljun, Janko Kos, Stanislav Gobec, Izidor Sosič","doi":"10.2478/acph-2025-0018","DOIUrl":"10.2478/acph-2025-0018","url":null,"abstract":"A significant amount of data about the different pharmacological activities of the established antimicrobial compound nitroxoline (8-hydroxy-5-nitroquinoline) is available in the scientific literature. On the other hand, its regioisomer 8-hydroxy-6-nitroquinoline was never characterised biochemically and the same also applies to their 1,2,3,4-tetrahydroquinoline analogues. Herein, we determined the influence of pyridine ring saturation and the position of the nitro group on various biochemical characteristics of compounds, such as metal-chelating properties, inhibition of methionine aminopeptidases (MetAPs) from Mycobacterium tuberculosis and human MetAP2, as well as antibacterial activities on Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis. In addition, inhibition of endopeptidase and exopeptidase activities of cathepsin B was determined, together with the ability of new nitroxo-line analogues to reduce intracellular collagen IV degradation. Substantially different biological activities were observed for the 6-nitro regioisomer of nitroxoline, as well as for both of their partially saturated counterparts.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"235-257"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploration of the chemical space of benzamide-based voltage-gated potassium channel K_v1.3 inhibitors. 苯酰胺基电压门控钾通道Kv1.3抑制剂的化学空间探索。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0019

Marzia Fois, Špela Pelcar, Joshua A Nasburg, Heike Wulff, Lucija Peterlin Mašič, Tihomir Tomašič

{"title":"Exploration of the chemical space of benzamide-based voltage-gated potassium channel Kv1.3 inhibitors.","authors":"Marzia Fois, Špela Pelcar, Joshua A Nasburg, Heike Wulff, Lucija Peterlin Mašič, Tihomir Tomašič","doi":"10.2478/acph-2025-0019","DOIUrl":"10.2478/acph-2025-0019","url":null,"abstract":"The voltage-gated potassium channel Kv1.3 is a key regulator of T-cell activation and a validated therapeutic target for autoimmune and inflammatory diseases. In this study, a ligand-based design strategy was employed to expand a library of benzamide-derived Kv1.3 inhibitors. Starting from a previously optimised thiophene-based inhibitor, structu ral modifications were introduced to the 2-methoxybenzamide moiety and the central tetrahydropyran or cyclohexane scaffold. A series of ketone, hydroxy, and carbamate derivatives was synthesised and evaluated for Kv1.3 inhibition using whole-cell patch-clamp electrophysiology. Structure-activity relationship analysis revealed that cis-isomers in the hydroxy series exhibited stronger activity than their trans counterparts, with some analogues displaying submicro-molar IC 50 values. In the carbamate series, trans-isomers were generally more potent, with trans-18 and trans-16 achieving IC 50 values of 122 and 166 nmol L-1, respectively. These results provide valuable insights into the design of Kv1.3 inhibitors and support further development of these compounds for immunomodulatory applications.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"219-233"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis, and evaluation of a novel fluorescent probe for competitive fluorescence polarization assay to screen galectin-8 inhibitors. 一种新型荧光探针的设计、合成和评价，用于竞争性荧光偏振法筛选半乳糖凝集素-8抑制剂。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0010

Edvin Purić, Marina Marinović, Zala Kojek, Barbro Kahl-Knutson, Hakon Leffler, Ulf J Nilsson, Marko Anderluh, Janez Mravljak

引用次数: 0

Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists. 6-（三氟甲基）嘧啶衍生物TLR8拮抗剂的优化。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0011

Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova

{"title":"Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists.","authors":"Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova","doi":"10.2478/acph-2025-0011","DOIUrl":"10.2478/acph-2025-0011","url":null,"abstract":"Toll-like receptors (TLRs) are essential for the innate immune system as they recognize pathogen-associated molecular patterns and trigger immune responses. Overactivation of TLR8 by endogenous nucleic acids is associated with the development of autoimmune diseases and promotes inflammatory responses. This study presents the design, synthesis, and evaluation of a series of TLR8 antagonists based on the optimization of previously reported 6-(trifluoromethyl)pyrimidin-2-amines, with targeted modifications to further explore structure-activity relationships (SAR) and increase potency. A two-step synthesis involving nucleophilic aromatic substitution and Suzuki coupling was used to prepare two series of new compounds. The biological evaluation revealed that compounds 14 and 26 exhibited promising TLR8 antagonistic activity with IC 50 values of 6.5 and 8.7 μmol L- 1, respectively. Compound 14 showed reduced cell viability at higher concentrations, while compound 26 showed no cytotoxic effects, making it a promising candidate for further investigation.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"159-183"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and evaluation of novel InhA inhibitors inspired by thiadiazole and tetrahydropyran series of inhibitors. 以噻二唑和四氢吡喃系列抑制剂为灵感的新型InhA抑制剂的开发和评价。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0016

Martina Hrast Rambaher, Nina Gradišek, Rok Frlan, Izidor Sosič, Aljoša Bolje, Jakob Kljun, Martin Juhás, Stanislav Gobec, Stane Pajk

{"title":"Development and evaluation of novel InhA inhibitors inspired by thiadiazole and tetrahydropyran series of inhibitors.","authors":"Martina Hrast Rambaher, Nina Gradišek, Rok Frlan, Izidor Sosič, Aljoša Bolje, Jakob Kljun, Martin Juhás, Stanislav Gobec, Stane Pajk","doi":"10.2478/acph-2025-0016","DOIUrl":"10.2478/acph-2025-0016","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading global health challenge, exacerbated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. One promising therapeutic target is the enzyme enoyl-acyl carrier protein reductase (InhA), which plays a vital role in the biosynthesis of mycolic acids, essential components of the bacterial cell wall. Direct inhibition of InhA offers a potential strategy for overcoming resistance mechanisms, particularly in cases where the activation of conventional drugs like isoniazid is compromised. This study investigates two novel series of InhA inhibitors based on thiadiazole and tetrahydropyran lead compounds, originally identified through high-throughput screening by GSK. Analogues were synthesised using the copper-catalysed azide-alkyne cycloaddition (CuAAC) click reaction, and their inhibitory activity was tested against InhA. Among the tested compounds, only one exhibited modest inhibitory activity, with an IC 50 of 11 µmol L-1, while others were inactive. Interestingly, during the synthetic efforts, a novel reaction was discovered between aryl methyl ketones and ethynylmagnesium bromide, yielding 1,3-diols, as confirmed by X-ray diffraction analysis. These findings underscore the challenges of optimising InhA inhibitors and highlight the potential of synthetic innovations in exploring new synthetic pathways.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"185-218"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0