Kyung-Sun Heo, Lan Phuong Phan, Nhi Thi Thao Le, Yujin Jin
{"title":"Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases","authors":"Kyung-Sun Heo, Lan Phuong Phan, Nhi Thi Thao Le, Yujin Jin","doi":"10.1007/s12272-025-01542-4","DOIUrl":"10.1007/s12272-025-01542-4","url":null,"abstract":"<div><p>Endothelial dysfunction plays a pivotal role in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, hypertension, heart failure, stroke, and peripheral artery disease. It disrupts vascular homeostasis, leading to reduced nitric oxide (NO) bioavailability, increased oxidative stress, and chronic inflammation, all of which collectively drive vascular damage, atherosclerotic plaque formation, and thrombosis. Additionally, shear stress-induced alterations in blood flow patterns, particularly disturbed flow (d-flow), aggravate endothelial dysfunction. Furthermore, the endothelial-to-mesenchymal transition (EndMT), a process in which endothelial cells acquire mesenchymal-like properties, contributes to vascular remodeling and accelerates CVD progression.</p><p>This review explores the significant role of epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs (ncRNAs), which serve as critical regulators of endothelial function in response to shear stress in endothelial dysfunction and the development of atherosclerosis. Furthermore, we discuss the pivotal role of endothelial dysfunction in cardiovascular and metabolic diseases, emphasizing the need for innovative therapeutic strategies beyond conventional treatments. In particular, we highlight the endothelial-protective mechanisms of emerging pharmacological agents, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, along with supporting clinical evidence demonstrating their efficacy in improving endothelial function and reducing cardiovascular risk.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"305 - 332"},"PeriodicalIF":6.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913942","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}
Mohammad Maqusood Alam, Sun Hak Lee, Sobia Wasim, Sang-Yoon Lee
{"title":"PET tracer development for imaging α-synucleinopathies","authors":"Mohammad Maqusood Alam, Sun Hak Lee, Sobia Wasim, Sang-Yoon Lee","doi":"10.1007/s12272-025-01538-0","DOIUrl":"10.1007/s12272-025-01538-0","url":null,"abstract":"<div><p>Abnormal α-synuclein aggregation is a key neuropathological hallmark of α-synucleinopathies, such as Parkinson’s disease (PD), multiple system atrophy (MSA), and several other neurological disorders, and closely contributes to pathogenesis. The primary characteristics of α-synucleinopathies are selective targeted neurodegeneration and the accumulation of Lewy pathologies. Specifically, α-synuclein positron emission tomography (PET) radiotracers target the fibrillar forms of the protein, thus enhancing early diagnosis and the evaluation of treatment effectiveness for various α-synucleinopathies. Therefore, in vivo detection of α-synuclein aggregates using targeted radiolabeled probes would aid in drug development, early diagnosis, and ongoing disease monitoring. As such, no promising α-synuclein biomarkers suitable for clinical applications have been reported. PET is a valuable non-invasive technique for imaging drug distribution in tissues and receptor occupancy at target sites in living animals and humans. Advances in PET biomarkers have significantly enhanced our understanding of the mechanisms underlying PD. This review summarizes recent ongoing efforts in the development of selective PET tracers for α-synuclein and discusses future perspectives.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"333 - 350"},"PeriodicalIF":6.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913926","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 review on bacteria-derived antioxidant metabolites: their production, purification, characterization, potential applications, and limitations","authors":"Nazli Pinar Arslan, Fakhrul Azad, Tugba Orak, Aysenur Budak-Savas, Serkan Ortucu, Pranav Dawar, Mustafa Ozkan Baltaci, Hakan Ozkan, Nevzat Esim, Mesut Taskin","doi":"10.1007/s12272-025-01541-5","DOIUrl":"10.1007/s12272-025-01541-5","url":null,"abstract":"<div><p>Antioxidants are organic molecules that scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby maintaining cellular redox balance in living organisms. The human body synthesizes endogenous antioxidants, whereas humans obtain exogenous antioxidants from other organisms such as plants, animals, fungi, and bacteria. This review primarily focuses on the antioxidant potential of natural metabolites and extracts from five major bacterial phyla, including the well-studied <i>Actinobacteria</i> and <i>Cyanobacteria</i>, as well as less-studied <i>Bacteroides</i>, <i>Firmicutes</i>, and <i>Proteobacteria</i><i>.</i> The literature survey revealed that the metabolites and the extracts with antioxidant activity can be obtained from bacterial cells and their culture supernatants. The metabolites with antioxidant activity include pigments, phycobiliproteins, polysaccharides, mycosporins-like amino acids, peptides, phenolic compounds, and alkaloids. Both metabolites and extracts demonstrate in vitro antioxidant capacity through radical-scavenging, metal-reducing, and metal-chelating activity assays. In in vivo models, they can scavenge ROS and RNS directly and/or indirectly eliminate them by enhancing the activities of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Due to their antioxidant activities, they may find applications in the cosmetic industry as anti-aging agents for the skin and in medicine as drugs or supplements for combating oxidative stress-related disorders, such as neurodegenerative diseases and diabetes. The literature survey also elucidated that some metabolites and extracts with antioxidant activity also exhibited strong antimicrobial properties. Therefore, we consider that they may have future applications in the treatment of infectious diseases, the preparation of pathogen-free healthy foods, and the extension of food shelf life.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"253 - 292"},"PeriodicalIF":6.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-025-01541-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913892","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 dynamic roles of macrophages extracellular traps (METs) in immune regulation","authors":"Yunjin Shin, Hanyoung Bae, Chaelin Lee, Inmoo Rhee","doi":"10.1007/s12272-025-01540-6","DOIUrl":"10.1007/s12272-025-01540-6","url":null,"abstract":"<div><p>Macrophages are crucial to innate immunity, eliminating pathogens and damaged tissues through phagocytosis and modulating immune responses. Recently, macrophage extracellular traps (METs) have been identified as chromatin-based structures composed of DNA and various immune-related proteins. While METs play a defensive role in trapping and neutralizing pathogens, they are also implicated in disease pathology, contributing to chronic inflammation, tissue damage, and immune dysregulation. The precise mechanisms regulating MET formation are still under investigation, but emerging evidence indicates the involvement of various regulatory factors. Dysregulated MET activity has been associated with various diseases, including autoimmune disorders, cancer, and neurological conditions. A deeper understanding of MET mechanisms and their pathological impact may offer novel therapeutic strategies. Given the limited number of reviews and articles on METs, this review provides valuable insights into MET formation, regulatory pathways, and their role in disease progression.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"293 - 304"},"PeriodicalIF":6.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787527","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}
Jihye You, Seunghwan Ha, Doyoung Kim, Hyoung-Geun Kim, Se Ha Kim, Ji-Hak Jeong, Changmin Oh, Nam-In Baek, Jong Hwa Jung, Jeong Ah Kim, You Mie Lee
{"title":"The inhibition of endothelial DLL4-NOTCH1 signaling by 2'-hydroxyflavanone enhances anti-PD-1 therapy in melanoma","authors":"Jihye You, Seunghwan Ha, Doyoung Kim, Hyoung-Geun Kim, Se Ha Kim, Ji-Hak Jeong, Changmin Oh, Nam-In Baek, Jong Hwa Jung, Jeong Ah Kim, You Mie Lee","doi":"10.1007/s12272-025-01539-z","DOIUrl":"10.1007/s12272-025-01539-z","url":null,"abstract":"<div><p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics; however limited patient responses necessitate combination strategies to improve therapeutic efficacy. Among potential combination partners, drugs targeting DLL4-NOTCH1 signaling pathway—a critical regulator of vascular function—show promise as angiogenesis modulators, but their clinical development have been hindered by safety concerns. To address this challenge, we adopted a novel approach by screening natural compounds with a long history of human consumption. Building upon our earlier findings, we identified three inhibitors of DLL4-NOTCH1 signaling: steppogenin, sanggenon F, and dehydrovomifoliol. Steppogenin inhibited both DLL4 and NOTCH1 activities, while sanggenon F and dehydrovomifoliol selectively suppressed DLL4 and NOTCH1 activity, respectively. We assessed their impact on key angiogenic processes, including endothelial cell migration, sprouting, and proliferation, and elucidated the relative contributions of selective DLL4 or NOTCH1 inhibition to the anti-angiogenic effect. By comparing structurally similar compounds, we identified the 2'-hydroxyflavanone moiety as a key element for DLL4 inhibition. Notably, combining steppogenin with an ICI demonstrated that a nature-derived angiogenesis inhibitor can boost the anti-cancer effect of ICI in a mouse melanoma allograft model. This comprehensive analysis of structure–activity relationships and in vivo therapeutic evaluation provides valuable insights into the development of novel anti-angiogenic compounds for combination therapy with ICIs in cancer treatment.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"351 - 364"},"PeriodicalIF":6.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762934","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}
Sonia Iranpour, Amir Abrishami, Amir Sh. Saljooghi
{"title":"Covalent organic frameworks in cancer theranostics: advancing biomarker detection and tumor-targeted therapy","authors":"Sonia Iranpour, Amir Abrishami, Amir Sh. Saljooghi","doi":"10.1007/s12272-025-01536-2","DOIUrl":"10.1007/s12272-025-01536-2","url":null,"abstract":"<div><p>In recent years, covalent organic frameworks (COFs) have garnered considerable attention in the field of onco-nanotechnology as a new type of nanoporous construct due to their promising physicochemical properties, ease of modification, and ability to be coupled with several moieties and therapeutic molecules. They can not only be used as biocompatible nanocarriers to deliver therapeutic payloads to the tumor zone selectively but can also be combined with a variety of therapeutic modalities to achieve the desired treatments. This review comprehensively presented recent achievements and progress in COF-based cancer diagnosis, detection, and cancer therapy to provide a better prospect for further research. Herein our primary emphasis lies on exploring the application of COFs as potential sensors for cancer-derived biomarkers that have received comparatively less attention in previous discussions. While the utilization of COFs in solid tumor therapy has faced significant challenges in scientific research and clinical applications, we reviewed the most promising features that underscore their potential in cancer theranostics.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 3","pages":"183 - 211"},"PeriodicalIF":6.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676710","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}
Jisoo Kang, Seol Hee Park, Mushira Khanam, Seo Bhin Park, Sumin Shin, Wonhyo Seo
{"title":"Impact of binge drinking on alcoholic liver disease","authors":"Jisoo Kang, Seol Hee Park, Mushira Khanam, Seo Bhin Park, Sumin Shin, Wonhyo Seo","doi":"10.1007/s12272-025-01537-1","DOIUrl":"10.1007/s12272-025-01537-1","url":null,"abstract":"<div><p>Numerous studies have examined the pathophysiological changes induced by chronic alcohol (ethanol) consumption and the underlying mechanisms, while much less attention has been devoted to understanding the health impacts of binge drinking. Binge drinking is defined as the excessive consumption of alcohol within a single drinking episode, and is the typical consumption pattern among young people in Western countries. While most young binge drinkers are not clinically alcohol dependent, binge drinking has emerged as a significant social and public health concern. The circulating alcohol consumed during binge episodes permeates cellular membranes throughout the body, exerting profound effects on multiple organs, and signaling pathways. Regular binge drinking eventually induces hepatic steatosis (fatty liver), initiates acute inflammation, and accelerates neutrophil infiltration, de novo lipogenesis, adipocyte death/lipolysis, and the production of nonoxidative alcohol metabolites, processes that synergize to damage liver tissue and impair liver function. Metabolic abnormalities such as diabetes and obesity can also exacerbate the progression of alcohol-related liver disease among binge drinkers. Several animal models have been developed to evaluate the pathophysiological changes resulting from binge drinking; however, the pathogenesis of binge drinking is not fully understood due to differences in alcohol metabolism between animal models and humans. Thus, given the high prevalence and severe health implications of binge drinking, there is an urgent need for comprehensive experimental and clinical investigations to unravel the associated pathophysiological changes. This review summarizes recent research findings on the impact of binge drinking, specifically focusing on its contributions to alcoholic liver injury.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 3","pages":"212 - 223"},"PeriodicalIF":6.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539840","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}
Ji Eun Kim, Yun Kim, Jiwon Bae, Eileen Laurel Yoon, Hyun Sung Kim, Sung Ryol Lee, Tae Hyun Yoon, Dae Won Jun
{"title":"A novel 11β-HSD1 inhibitor ameliorates liver fibrosis by inhibiting the notch signaling pathway and increasing NK cell population","authors":"Ji Eun Kim, Yun Kim, Jiwon Bae, Eileen Laurel Yoon, Hyun Sung Kim, Sung Ryol Lee, Tae Hyun Yoon, Dae Won Jun","doi":"10.1007/s12272-025-01534-4","DOIUrl":"10.1007/s12272-025-01534-4","url":null,"abstract":"<div><p>11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates hepatic glucose output and is implicated in liver fibrosis. We aimed to investigate the anti-fibrotic effect of a novel 11β-HSD1 inhibitor in a thioacetamide (TAA)-induced liver fibrosis mouse model. Mice were administered TAA for 19 weeks and treated with 11β-HSD1 inhibitor for the last 9 weeks. Treatment with 11β-HSD1 inhibitor significantly reduced fibrosis area, alanine aminotransferase, and aspartate aminotransferase levels compared to the TAA-only group. Inhibition of 11β-HSD1 led to a decrease in intracellular cortisol levels, which suppressed the activation of hepatic stellate cells. RNA sequencing revealed significant downregulation of the Notch signaling pathway, including reduced expression of Notch ligands and receptors, as well as downstream genes. Furthermore, 11β-HSD1 inhibition enhanced NK cell-mediated immune responses, as indicated by the upregulation of NK cell-related genes and increased NK cell populations confirmed by mass cytometry. This increase in NK cell activity contributed to the clearance of activated HSCs and the attenuation of fibrosis. These findings suggest that 11β-HSD1 inhibition alleviates liver fibrosis through Notch pathway suppression and enhancement of NK cell-mediated immune responses. Our results support the therapeutic potential of a novel 11β-HSD1 inhibitor for treating liver fibrosis.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 2","pages":"166 - 180"},"PeriodicalIF":6.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424898","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}
Mona F. Mahmoud, Mohamed El-Nagar, Hany M. El-Bassossy
{"title":"Retraction Note: Anti-inflammatory effect of atorvastatin on vascular reactivity and insulin resistance in fructose fed rats","authors":"Mona F. Mahmoud, Mohamed El-Nagar, Hany M. El-Bassossy","doi":"10.1007/s12272-025-01535-3","DOIUrl":"10.1007/s12272-025-01535-3","url":null,"abstract":"","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 3","pages":"251 - 251"},"PeriodicalIF":6.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397902","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}
Ahmed Elkamhawy, Usama M. Ammar, Minkyoung Kim, Anam Rana Gul, Tae Jung Park, Kyeong Lee
{"title":"Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening","authors":"Ahmed Elkamhawy, Usama M. Ammar, Minkyoung Kim, Anam Rana Gul, Tae Jung Park, Kyeong Lee","doi":"10.1007/s12272-025-01533-5","DOIUrl":"10.1007/s12272-025-01533-5","url":null,"abstract":"<div><p>Raf kinase enzymes are often dysregulated in melanoma. While sorafenib demonstrates strong activity against wild-type B-Raf, it fails to effectively inhibit the mutated form of B-Raf. In this study, sorafenib served as a lead compound for the development of new derivatives designed to enhance inhibitory activity across multiple Raf isoforms (pan-Raf inhibitors). Novel naphthalene-based diarylamide derivatives were subsequently designed, synthesized, and evaluated for their biological activity against various Raf kinase isoforms and the melanoma A375 cell line. Among these, compound <b>9a</b>, containing a difluoromethoxy group, demonstrated strong inhibitory activity across B-Raf<sup>WT</sup>, B-Raf<sup>V600E</sup>, and c-Raf. Additionally, it induced G2/M phase arrest and triggered dose-dependent apoptosis, effectively suppressing both cell proliferation and survival. Compound <b>9a</b> also exhibited high selectivity for Raf isoforms with minimal off-target effects, underscoring its specificity and therapeutic potential for Raf-driven malignancies.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 2","pages":"150 - 165"},"PeriodicalIF":6.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-025-01533-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370348","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}