Biomedicine & Pharmacotherapy最新文献

{"title":"Chronic administration of tetrahydrofuran extracts of Cochlospermum vitifolium (Wild) Sprengel in a mouse diabetes model: Hypoglycemic, antioxidant, and genoprotective effects","authors":"Santiago José Guevara-Martínez ,&nbsp;Francisco Villanueva-Mejía ,&nbsp;Tomás Alejandro Fregoso-Aguilar ,&nbsp;Adalberto Zamudio-Ojeda ,&nbsp;Rafael Herrera-Bucio ,&nbsp;Fredy Geovannini Morales-Palacios","doi":"10.1016/j.biopha.2025.118132","DOIUrl":"10.1016/j.biopha.2025.118132","url":null,"abstract":"<div><div>Diabetes and its complications represent a major global health burden, contributing to rising mortality rates, escalating healthcare costs, and an increasing prevalence worldwide. This has driven renewed interest in traditional medicine as a complementary approach to disease management. <em>Cochlospermum vitifolium</em> (Wild) Sprengel, a medicinal plant traditionally used to treat kidney pain, liver disorders (including hepatitis C and jaundice), and metabolic syndrome, has demonstrated promising antidiabetic potential. Previous studies report hypoglycemic effects in both <em>in vitro</em> and short-term <em>in vivo</em> models. In this study, we evaluated the hypoglycemic activity of tetrahydrofuran (THF) extracts from <em>C. vitifolium</em> heartwood and bark in mice over a six-week period (500 mg/kg dose). The heartwood extract exhibited notable antioxidant activity, scavenging over 50 % of DPPH radicals at 3.2 mg/mL, while the bark extract showed higher potency at 1.5 mg/mL. Both extracts demonstrated genoprotective effects at doses of 250 and 500 mg/kg, mitigating damage from mutagenic agents. Notably, the heartwood extracts significantly reduced blood glucose levels from &gt; 300 mg/dL to &lt; 100 mg/dL, whereas the bark extract had no significant hypoglycemic effect. These findings suggest that <em>C. vitifolium</em> extracts, particularly from the heartwood, may modulate oxidative stress-related pathways implicated in chronic degenerative diseases such as diabetes. Further research is warranted to elucidate the underlying mechanisms and long-term safety profile of these extracts.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118132"},"PeriodicalIF":6.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Comparative analysis of novel modified drug delivery systems for improving the oral bioavailability of water-insoluble tadalafil using copovidone, TPGS and hydroxypropyl-β-cyclodextrin” [Biomed. Pharmacother. 186 (2025) 118039]","authors":"Fakhar ud Din ,&nbsp;Dong Shik Kim ,&nbsp;Jung Suk Kim ,&nbsp;Seunghyun Cheon ,&nbsp;Seonghyeon Park ,&nbsp;Sanghyun Woo ,&nbsp;Mi Ran Woo ,&nbsp;Zakir Ali ,&nbsp;Jong Oh Kim ,&nbsp;Sung Giu Jin ,&nbsp;Han-Gon Choi","doi":"10.1016/j.biopha.2025.118127","DOIUrl":"10.1016/j.biopha.2025.118127","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118127"},"PeriodicalIF":6.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Mechanisms of bone regeneration repair and potential and efficacy of small molecule drugs” [Biomed. Pharmacother. 187 (2025) 118070]","authors":"Ke Zhang ,&nbsp;Hao Li ,&nbsp;Tao Wang ,&nbsp;Fanchao Li ,&nbsp;Zhihong Xie ,&nbsp;Hong Luo ,&nbsp;Xuesong Zhu ,&nbsp;Pengde Kang ,&nbsp;Qinglin Kang ,&nbsp;Fei Zhang ,&nbsp;Wuxun Peng","doi":"10.1016/j.biopha.2025.118116","DOIUrl":"10.1016/j.biopha.2025.118116","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118116"},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional interactions between St. John´s wort and gut microbiome: Potential implications on gut-brain-axis","authors":"Maria-Eleni Grafakou ,&nbsp;Eva-Maria Pferschy-Wenzig ,&nbsp;Heba Aziz-Kalbhenn ,&nbsp;Olaf Kelber ,&nbsp;Christine Moissl-Eichinger ,&nbsp;Rudolf Bauer","doi":"10.1016/j.biopha.2025.118111","DOIUrl":"10.1016/j.biopha.2025.118111","url":null,"abstract":"<div><div>Emerging evidence highlights the role of gut microbiome in mental health disorders, including depression, raising the question whether the action of antidepressants could be mediated, at least in part, via the microbiome-gut-brain axis. To explore this, we subjected a St. John's wort extract (STW 3-VI), clinically proven to be effective in mild to moderate depression, to a model of the upper and lower intestinal tract, including static <em>in vitro</em> predigestion followed by <em>ex vivo</em> incubation with human microbiota samples. To cover the interindividual diversity of gut microbiome composition, fecal samples from ten healthy volunteers were used. Although unchanged levels of most annotated compounds were observed during simulated upper intestinal tract digestion, incubation with fecal microbiota led to a significant change of the chemical profile of the extract. While hyperforins remained stable, flavonoids and hypericins were rapidly biotransformed, suggesting that they may act as prodrugs. Several metabolites were formed, many of which are known to be involved in gut-brain communication. Differential abundance analysis revealed significant changes in microbiome composition, particularly for taxa known to be potentially associated with depression. Among others, the <em>Firmicutes</em>/<em>Bacteroidetes</em> ratio, known to be lowered in depressive patients, was increased. Functional profiling revealed modulation of pathways involved in gut-brain communication, such as tyrosine and tryptophan metabolism. These bidirectional interactions suggest for the first time the gut microbiome as a potential mediator of the pharmacological effects of St. John's wort extracts via the microbiome-gut-brain axis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118111"},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha lipoic acid modulates metabolic reprogramming in breast cancer stem cells enriched 3D spheroids by targeting phosphoinositide 3-kinase: In silico and in vitro insights","authors":"Bandana Chakravarti ,&nbsp;Manendra Singh Tomar ,&nbsp;Faizan Abul Qais ,&nbsp;Sana Raza ,&nbsp;K.M. Abdullah ,&nbsp;Gunjan Sharma ,&nbsp;Archana Tewari ,&nbsp;Abhishek Yadav ,&nbsp;Pratima Gupta ,&nbsp;Naibedya Chattopadhyay ,&nbsp;Ashutosh Shrivastava ,&nbsp;Rohit Anthony Sinha ,&nbsp;Jawed Akhtar Siddiqui","doi":"10.1016/j.biopha.2025.118121","DOIUrl":"10.1016/j.biopha.2025.118121","url":null,"abstract":"<div><div>Breast cancer stem cells (BCSCs) are a unique subpopulation of tumor cells driving tumor resistance, progression, metastasis, and recurrence. Reprogrammed cellular metabolism and key signaling pathways, including Wnt/β-catenin, TGF-β, STAT3, and PI3K/AKT/mTOR pathway play a vital role in maintaining BCSCs. Importantly, PI3K/Akt/mTOR pathway regulates metabolism, survival, growth, and invasion, with PIK3CA, encoding the PI3K catalytic subunit p110α, the most frequently mutated gene in breast cancer. This study investigates the effects of alpha-lipoic acid (LA) on the metabolic profile of BCSCs, focusing on its interaction with PI3K signaling. LA was found to bind PI3K, disrupting cancer-associated metabolic pathways and significantly inhibiting BCSC metabolism. Metabolomic analysis of MCF-7 and MDA-MB-231-derived breast cancer spheroids showed LA-induced metabolic shifts. In MCF-7 spheroids, LA induced upaccumulation of 15 metabolites and downaccumulation of 5, while in MDA-MB-231 spheroids, it induced upaccumulation of 3 and downaccumulation of 16. LA also enhanced the sensitivity of breast cancer spheroids to doxorubicin (Dox), demonstrating a synergistic effect. Mechanistically, LA modulates the PI3K/Akt/mTOR pathway, impairing cell survival and proliferation. These findings highlight the potential of LA as a therapeutic agent for reprogramming cancer metabolism and enhancing chemotherapy efficacy. These results provide a strong rationale for incorporating LA into combination therapy strategies for breast cancer treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118121"},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel dihydrochalcone from Fissistigma latifolium targets STAT3 and survivin to overcome multidrug resistance cancers in vitro and in vivo","authors":"I-Ting Wu ,&nbsp;Ying-Tzu Chang ,&nbsp;Ching-Hui Su ,&nbsp;Yu-Hsuan Lan ,&nbsp;Chin-Chuan Hung","doi":"10.1016/j.biopha.2025.118125","DOIUrl":"10.1016/j.biopha.2025.118125","url":null,"abstract":"<div><h3>Background</h3><div>Multidrug resistance (MDR) remains a significant challenge in cancer chemotherapy, with no FDA-approved drugs currently available for its treatment. Natural chalcones, known for their diverse bioactivities, have emerged as potential therapeutic candidates.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the potential of 4,6-dimethoxy-2,5-quinodihydrochalcone (DODHC), a compound derived from <em>Fissistigma latifolium</em>, in overcoming MDR in cancer and to elucidate its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>The reversal effects of DODHC on MDR were evaluated using cytotoxicity assays. The molecular mechanisms were explored through apoptosis- and cell cycle-related assays, STAT3 ELISA, western blotting, docking simulations, and a zebrafish model. The impact of DODHC on P-glycoprotein (P-gp) activity was assessed using the Calcein-AM uptake assay.</div></div><div><h3>Results</h3><div>DODHC promoted apoptosis in MDR cancer cells by suppressing survivin expression and activating the extrinsic apoptotic pathway. It also induced G2/M phase cell cycle arrest by downregulating cell division control protein 2 (<em>CDC2</em>) and cyclin B1 (<em>CCNB1</em>), thereby inhibiting cell proliferation. Additionally, DODHC reduced both total and phosphorylated STAT3 levels in MDR cancer cells without affecting P-gp activity. In vivo, DODHC significantly inhibited tumor growth in MDR cancer models, both as a monotherapy and in combination with paclitaxel.</div></div><div><h3>Conclusion</h3><div>This study highlights DODHC as a dual inhibitor of STAT3 and survivin, demonstrating its potential as a promising candidate for the treatment of MDR cancers.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118125"},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin restores mitochondrial bioenergetics and redox homeostasis through modulation of mitochondrial biogenesis and dynamics in patient derived cultured fibroblasts and an animal model of molybdenum cofactor deficiency","authors":"Morgana Brondani ,&nbsp;Rafael T. Ribeiro ,&nbsp;Camila V. Pinheiro ,&nbsp;Christofer I.H. Hoffmann ,&nbsp;Manuela B. Marcuzzo ,&nbsp;Al-Walid Mohsen ,&nbsp;Moacir Wajner ,&nbsp;Bianca Seminotti ,&nbsp;Jerry Vockley ,&nbsp;Guilhian Leipnitz","doi":"10.1016/j.biopha.2025.118123","DOIUrl":"10.1016/j.biopha.2025.118123","url":null,"abstract":"<div><div>Molybdenum cofactor deficiency (MoCD) is an inborn error of sulfur metabolism caused by inactivating variants in the genes encoding enzymes of the molybdenum cofactor biosynthetic pathway. Patients present with accumulation of sulfite in the brain with secondary mitochondrial bioenergetics and severe neurological manifestations. To investigate the pathophysiology of this disorder, we evaluated mitochondrial and redox homeostasis in fibroblasts derived from a patient with MoCD type A (MOCS1 deficiency) and in an animal model based on the intracerebroventricular administration of sulfite in Wistar rats. Since treatment for MoCD is largely ineffective, we also investigated the effects of metformin, an antidiabetic drug with neuroprotective potential. Reduced basal, maximal, and ATP-linked respiration and reserve respiratory capacity were verified in MOCS1 deficient fibroblasts. The protein content of MFN1/2, OPA1, DRP1, and NRF1 was also reduced, whereas p-DRP1 (Ser 637) was increased. Superoxide levels were elevated in these cells. Metformin treatment reversed these changes. Further, the p-AMPK/T-AMPK protein ratio and the expression of <em>PRKAA1</em>, <em>PPARGC1A</em>, <em>SIRT1, DNM1L,</em> and <em>mitofusin 1</em> were increased by metformin in the deficient cells. Sulfite administration into rat brain disturbed the antioxidant defenses, and tricarboxylic acid cycle and electron transfer chain function in the striatum, cerebral cortex and cerebellum. Metformin prevented this bioenergetic dysfunction. Our findings show that metformin elicits positive effects in the brain of sulfite-treated rats and in the MOCS1 deficient cell line by modulating mitochondrial biogenesis and fission, identifying potential therapeutic intervention opportunities in MoCD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118123"},"PeriodicalIF":6.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levosimendan mitigates renal fibrosis via TGF-β1/Smad axis modulation in UUO rats","authors":"Rohan Bhadange,&nbsp;Neha Dagar,&nbsp;Anil Bhanudas Gaikwad","doi":"10.1016/j.biopha.2025.118124","DOIUrl":"10.1016/j.biopha.2025.118124","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is characterized by kidney fibrosis involving epithelial-mesenchymal transition (EMT), and extracellular matrix (ECM) accumulation, and often leads to end-stage kidney disease (ESKD). Currently, available therapies are not uniformly effective and lead to serious adverse effects. Levosimendan (LVS), a calcium sensitizer and an inodilator, manages cardiac failure. We aimed to evaluate the renoprotective effect of LVS on unilateral ureteral obstruction (UUO)-induced CKD in male Sprague-Dawley (SD) rats and exogenous transforming growth factor-β1 (TGF-β1)-induced fibrosis in NRK-52E cells. Rats were randomly grouped as normal control (NC), sham, UUO and UUO + LVS (3 mg/kg, <em>p.o., o.d.</em>) for 21 days. All animals were sacrificed post-treatment, and plasma, urine and kidney specimens were utilized for biochemistry, histology, immunohistochemistry and immunoblotting. Moreover, exogenous TGF-β1 was used to stimulate kidney fibrosis in NRK-52E cells and treated with LVS (10 µM) for 48 h. The <em>in-vitro</em> samples were collected for cell morphology, viability, immunofluorescence and immunoblotting. LVS treatment significantly improved the kidney mass, plasma and urine creatinine, BUN, urine urea nitrogen and plasma proteins levels of TGF-β1 and fibronectin. Histology revealed a significant decrease in tubular necrosis, glomerulosclerosis and tubulointerstitial fibrosis in LVS-treated rats. Moreover, LVS treatment remarkably downregulated the levels of α-SMA, vimentin, p-Smad 2/3 and upregulated E-cadherin in UUO rats, decreased Smad 4, collagen I, β-catenin, and MMP-7-mediated ECM and increased Smurf 2 and Smad 7 in NRK-52E cells. LVS inhibits EMT and ECM turnover via TGF-β1/Smad axis modulation, highlighting the potential clinical use of LVS for CKD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118124"},"PeriodicalIF":6.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene microplastic induced airway hyper-responsiveness, and pulmonary inflammation are mitigated by bronchom treatment in murine model of lung disease","authors":"Acharya Balkrishna ,&nbsp;Aakanksha Tiwari ,&nbsp;Sandeep Sinha ,&nbsp;Ankita Kumari ,&nbsp;Vivek Gohel ,&nbsp;Rishabh Dev ,&nbsp;Kunal Bhattacharya ,&nbsp;Anurag Varshney","doi":"10.1016/j.biopha.2025.118122","DOIUrl":"10.1016/j.biopha.2025.118122","url":null,"abstract":"<div><div>Microplastics are global menace-associated with respiratory damages. The objective of this study was to investigate the airway hyper-responsiveness (AHR) and inflammation induced by polystyrene microplastic (PSMPs) in male C57BL/6 mice and its modulation by ‘Bronchom’, an herbal medicine. For the study, animals were pre-treated with varying doses of Bronchom before 21-day exposure to PSMPs, followed by assessment of pulmonary damages. PSMPs exposure in mice significantly induced AHR to methacholine, represented by elevated respiratory resistance, and reduced lung compliance. PSMPs also induced influx of pro-inflammatory cells and release of pro-inflammatory mediators TNF-α, IL-1β, IL-5, IL-6 and MIP-2α in the bronchoalveolar lavage of PSMPs-exposed animals. Histopathological analysis confirmed leukocyte infiltration and mild fibrosis in the lung tissues of PSMPs-exposed animals. PSMPs-exposure also enhanced mRNA expression of pro-inflammatory biomarkers in lung tissues. Bronchom-treated mice showed significant protection against the PSMPs-induced AHR, inflammatory cell influx and cytokine expression, along with histopathological changes in dose-dependent manner. Pirfenidone used as a positive control showed beneficiary effects against PSMPs-induced respiratory distress. Interestingly, FTIR spectroscopy of the Bronchom-treated mice lung tissues indicated dose-dependent reduction in PSMPs-specific transmittance signatures, suggesting their reduced bioaccumulation. In human THP-1 macrophages, Bronchom also attenuated PSMPs-induced TNF-α and IL-6 cytokines release. Ultra-high-performance-liquid-chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS) identified 80 phytochemicals, associated with robust anti-inflammatory and anti-oxidant profile. These results indicated that Bronchom effectively mitigates PSMPs-induced respiratory distress-associated inflammation and PSMPs bioaccumulation in lung tissue, likely due to its rich phytochemical composition. This study highlights Bronchom as a promising herbal intervention against microplastic-associated pulmonary ailments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118122"},"PeriodicalIF":6.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptide Y receptors 1 and 2 as molecular targets in prostate and breast cancer therapy","authors":"Katarina Tomić ,&nbsp;Nina Kostevšek ,&nbsp;Sergio Romeo ,&nbsp;Ivan Bassanini","doi":"10.1016/j.biopha.2025.118117","DOIUrl":"10.1016/j.biopha.2025.118117","url":null,"abstract":"<div><div>Recent advances have revealed the overexpression of Neuropeptide Y (NPY) receptors in multiple cancers, positioning them as attractive molecular targets for cancer diagnostics and therapeutics. Despite this, a comprehensive roadmap for the rational development of anticancer agents targeting NPY receptors remains lacking. Therefore, we present the characteristics of NPY receptor subtypes, their abundance, and the correlation of their expression in different cancer types. It was found that NPY receptor subtypes 1 and 2 were extensively studied, especially in connection with breast and prostate cancer. Many tumors express NPYR, but only breast cancer tissue shows a significant difference in NPYR subtype expression levels between tumor and normal tissues, and, therefore, can represent a promising target. In the context of anticancer therapy, this review provides key findings from the use of wild-type and synthetic NPY analogs. We highlight the critical residues in the NPY sequence that play a critical role in interactions with receptors and provide the recent literature findings on NPY analogues as efficient and specific cancer-targeting agents. Potential solutions to improve NPY analogs' stability are provided, such as sequence modifications of linear peptides, peptide stapling, and conjugation for drug delivery systems. In general, NPY treatment can not be used efficiently as a single therapy but as a combinatorial therapy with anticancer drugs to improve the specificity of the treatment via high-affinity binding to the cancer cells and sensitizing them to chemotherapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118117"},"PeriodicalIF":6.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}