Biomedicine & Pharmacotherapy最新文献

{"title":"Therapeutic potential of heat-killed Enterococcus faecalis (EC-12) para-probiotic in reversing maternal separation-triggered social deficit in mice","authors":"Eman A. Mady ,&nbsp;Hussein M. El-Husseiny ,&nbsp;Yuko Makioka-Itaya ,&nbsp;Shodai Ishikawa ,&nbsp;Ryo Inoue ,&nbsp;Chunmei Li ,&nbsp;Yuki Yamamoto ,&nbsp;Kentaro Nagaoka","doi":"10.1016/j.biopha.2025.118513","DOIUrl":"10.1016/j.biopha.2025.118513","url":null,"abstract":"<div><div>Early life stress due to maternal separation (MS) disrupts the gut–brain axis (GBA), leading to long-term neurobiological and behavioral deficits, particularly social behavior impairments. Although various probiotics have shown therapeutic potential, the efficacy of heat-killed <em>Enterococcus faecalis</em> EC-12 (EC-12) as a para-probiotic remains largely unknown. This study aimed to evaluate the therapeutic potential of EC-12 in reversing MS-induced behavioral and molecular abnormalities in mice. Male C57BL/6 J mice were subjected to MS from postnatal days (PD) 3–20 and then divided into four groups with or without EC-12 supplementation. After five weeks of EC-12 administration, behavioral assessments were conducted, followed by prefrontal cortex transcriptomic analysis, cecal content microbiomic analysis, and serum and cecal content metabolomic analyses. EC-12 supplementation significantly restored social interaction behavior in mice with MS without affecting anxiety- or depression-like phenotypes. Transcriptome analysis revealed significant upregulation of vasopressin-related genes (<em>Trpv4</em> and <em>Ecrg4</em>), with vasopressin secretion being the most enriched biological pathway. EC-12 also increased the levels of L-tryptophan and L-tyrosine and upregulated <em>Tph2</em> gene expression. The gut microbiota composition was substantially reshaped in MS-EC-12 mice, with enrichment of beneficial genera (<em>Blautia</em>, <em>Dubosiella</em>, <em>Romboutsia</em>), and fecal metabolomics revealed increased levels of phenylacetic acid, glycerol 3-phosphate, and pectin, with significant activation of glycerolipid metabolism. These findings suggest that heat-killed EC-12 can mitigate early life stress-induced social deficits through microbiota- and metabolite-mediated modulation of GBA and may serve as a promising para-probiotic intervention for neurodevelopmental disorders.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118513"},"PeriodicalIF":7.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932546","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":"In vitro screening of synbiotics based on a four-strain probiotic blend and their therapeutic potential for ulcerative colitis","authors":"Jiahao Liao ,&nbsp;Ying Guo ,&nbsp;Zhuoya Guo ,&nbsp;Xianqian Zhang ,&nbsp;Xiaoqiong Li ,&nbsp;Jian Kuang ,&nbsp;Jianqiang Li ,&nbsp;Xiangyu Bian ,&nbsp;Weiwei Wang ,&nbsp;Jinjun Li","doi":"10.1016/j.biopha.2025.118521","DOIUrl":"10.1016/j.biopha.2025.118521","url":null,"abstract":"<div><div>This study explores the therapeutic effects of synbiotics on ulcerative colitis (UC) using an in vitro fermentation model and a Dextran Sulfate Sodium (DSS)-induced UC mouse model. We assessed the impact of synbiotics on probiotic proliferation, short-chain fatty acid (SCFA) production, metabolic regulation, and intestinal barrier function. Fructooligosaccharide (FOS) and Inulin (INU) significantly promoted probiotic growth and increased SCFA production, especially acetate, propionate, butyrate, and isobutyrate (<em>p</em> &lt; 0.01). Metabolomics analysis revealed compound probiotics (CP)+FOS and CP+INU significantly modulated probiotic metabolic activity (<em>p</em> &lt; 0.05), affecting metabolites and related pathways. In the DSS-induced UC mouse model, the combination of CP+FOS and CP+INU alleviated UC symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while increasing spleen index. Histological analysis showed synbiotics preserved colonic crypts, reduced inflammatory cell infiltration, and enhanced intestinal barrier function, with the CP+FOS group showing the most pronounced effects. Immunohistochemistry revealed restored expression of tight junction proteins (Claudin-1, Occludin, ZO-1), further supporting intestinal barrier protection. The synbiotic combination modulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory IL-10 (<em>p</em> &lt; 0.01). SCFA analysis showed significant increases in all measured SCFAs (<em>p</em> &lt; 0.01). Correlation analysis indicated strong positive associations between SCFAs, body weight, colon length, and IL-10. In conclusion, the synbiotic combination of FOS and INU shows significant potential in alleviating UC symptoms, repairing the intestinal barrier, and modulating inflammation, supporting its potential as an adjunct or alternative UC therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118521"},"PeriodicalIF":7.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933024","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":"Bacterial exopolysaccharides and live biotherapeutics: Orchestrating immune modulation and therapeutic potential in the gut microbiome era","authors":"Arpit Shukla ,&nbsp;Mark Tangney","doi":"10.1016/j.biopha.2025.118510","DOIUrl":"10.1016/j.biopha.2025.118510","url":null,"abstract":"<div><div>Microbial exopolysaccharides (EPS) are emerging as critical effector molecules orchestrating host immunity. Their remarkable structural diversity, driven by variations in monosaccharide composition, charge, and glycosidic linkages, dictates potent immunomodulatory functions through specific interactions with host pattern recognition receptors (CLRs, TLRs), triggering defined cellular responses and cytokine profiles, often with minimal toxicity. Beyond direct immune effects, EPS shape the gut environment by fortifying barrier integrity and acting as prebiotics. This therapeutic potential can be harnessed via Live Biotherapeutics (LBs) as natural producers, or through purified or rationally engineered EPS for targeted intervention. Cutting-edge synthetic biology and production strategies aim to unlock this potential, though significant structure-function knowledge gaps and scalability challenges in linking specific structural motifs to predictable immune outcomes and in developing scalable, reproducible production methods remain. This review synthesizes and critically evaluates current understanding, focusing specifically on the immunomodulatory EPS produced by gut-commensal and probiotic bacteria. We highlight the promise of these molecules as therapeutics and provide a roadmap for the rational design of next-generation immunotherapies, including engineered LBs that produce tailored EPS <em>in situ</em> to target the gut ecosystem.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118510"},"PeriodicalIF":7.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932548","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":"Subclinical tubular kidney injury associated with immune checkpoint inhibitors and cisplatin treatment: Diagnosis through urinary biomarkers","authors":"Javier Tascón ,&nbsp;Alfredo G. Casanova ,&nbsp;Laura Vicente-Vicente ,&nbsp;Marta Prieto ,&nbsp;Ana I. Morales","doi":"10.1016/j.biopha.2025.118430","DOIUrl":"10.1016/j.biopha.2025.118430","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) represent a major advance in cancer treatment due to their efficacy and safety profile. However, they are not free of side effects, including nephrotoxicity, which worsens prognosis. Diagnosis of renal injury based on clinical findings has limitations in predicting and identifying the type of damage. Biopsy remains the only definitive technique, though it is invasive and carries risks. Thus, new diagnostic approaches using urinary biomarkers are needed. Our hypothesis is that the renal damage associated with ICIs could be subclinical and not detectable by the tests used in clinical practice. Therefore, the aim was to associate the excretion of urinary biomarkers with subclinical renal damage in an experimental mouse model of treatment with ICIs and chemotherapy. A pathophysiological study was also performed to interpret the relationship between the biomarkers and the type of damage. Our results showed that the combined therapy of ICIs and cisplatin causes subclinical tubular damage, as evidenced by the excretion of albumin, NGAL and KIM-1, and suggest that cisplatin-induced renal damage is potentiated by the administration of ICIs. Diagnosis using these urinary biomarkers could be an optimal tool to detect damage at an earlier stage and improve patient management. In turn, ICIs promote an inflammatory process, as demonstrated by the biomarkers TNF-α, IL-9, CD8 and CD3, which would be involved in the development of kidney damage. Our findings open the possibility of studying their usefulness as differential diagnostic tools to identify characteristic inflammatory lesions of acute tubulo-interstitial nephritis, avoiding renal biopsy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118430"},"PeriodicalIF":7.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932551","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":"A consensus HA DNA vaccine targeting clade 2.3.4.4 H5Nx influenza viruses provides broad cross-clade protection in mice and ferrets","authors":"Chang-Ung Kim ,&nbsp;Won-Suk Choi ,&nbsp;Pureum Lee ,&nbsp;Ju Hwan Jeong ,&nbsp;Yong Bok Seo ,&nbsp;Young Woo Choi ,&nbsp;Myung Ho Sohn ,&nbsp;So-Young Choi ,&nbsp;Ahn Young Jeong ,&nbsp;Min-Suk Song ,&nbsp;Doo-Jin Kim","doi":"10.1016/j.biopha.2025.118485","DOIUrl":"10.1016/j.biopha.2025.118485","url":null,"abstract":"<div><div>Recurrent outbreaks of highly pathogenic avian influenza (HPAI) H5Nx viruses in birds pose a threat to human health due to their zoonotic potential. This underscores the urgent need for effective vaccines to mitigate the pandemic risk from evolving H5Nx viruses. We developed a DNA vaccine encoding a consensus hemagglutinin (HA) from clade 2.3.4.4 H5Nx viruses [pGX-27/HA (2.3.4.4)] and evaluated its immunogenicity and protective efficacy in mice and ferrets. Vaccination elicited strong neutralizing antibody and T cell responses, protecting mice against lethal challenge with homologous viruses. Unlike formalin-inactivated vaccines, the DNA vaccine conferred CD8⁺ T cell–mediated cross-protection against divergent clades 2.2.1.2 and 2.3.2.1. In ferrets, the vaccine induced neutralizing antibodies and conferred protective immunity, indicating translational potential. These results suggest that the HA (2.3.4.4) DNA vaccine provides broad immunity against multiple H5Nx clades and offers insights for developing next-generation vaccines against potential zoonotic influenza threats.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118485"},"PeriodicalIF":7.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932550","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":"Human sclerostin-inspired short peptides reverse osteoporosis and suppress joint degeneration in osteoarthritis via opposing Wnt pathways","authors":"Shivani Sharma ,&nbsp;Chirag Kulkarni ,&nbsp;Neeraj K. Verma ,&nbsp;Swati Srivastava ,&nbsp;Rosebin Babu ,&nbsp;Anupam Ghosh ,&nbsp;Nandita Dasgupta ,&nbsp;Arvind Gupta ,&nbsp;Simran Preet Kaur ,&nbsp;Leena Sapra ,&nbsp;Swati Rajput ,&nbsp;Sreyanko Sadhukhan ,&nbsp;Konica Porwal ,&nbsp;Devesh P. Verma ,&nbsp;Mohd. Sayeed ,&nbsp;Asit R. Mridha ,&nbsp;Madan M. Godbole ,&nbsp;Kumaravelu Jagavelu ,&nbsp;Rupesh K. Srivastava ,&nbsp;Aravind S. Kshatri ,&nbsp;Naibedya Chattopadhyay","doi":"10.1016/j.biopha.2025.118501","DOIUrl":"10.1016/j.biopha.2025.118501","url":null,"abstract":"<div><div>Sclerostin, a key regulator of Wnt/β-catenin signaling, exhibits dual therapeutic potential in bone disorders: its inhibition promotes bone formation in osteoporosis, while its mimicry suppresses aberrant bone growth in osteoarthritis (OA). Using structural insights from NMR studies, we identified two sclerostin-derived peptides: SC-1 (an 18-mer) from loop 2, and SC-3 (a 14-mer) from loop 3. Molecular modeling showed that SC-1 binds to the first ectodomain of LRP6, potentially displacing sclerostin through competitive inhibition to activate Wnt signaling. In contrast, SC-3 occupies the sclerostin/Wnt-binding site on the second ectodomain, thereby mimicking sclerostin's inhibitory function. In ovariectomized (OVX) rats, SC-1 (100 µg/kg) restored bone mineral density (BMD), trabecular architecture, and mechanical strength to sham levels, outperforming teriparatide by coupling bone formation with resorption suppression. In chronic kidney disease-induced osteoporosis, SC-1 reversed osteomalacia and improved renal parameters. Safety assessments showed that SC-1 lacked immunogenicity (no increase in CD11b+ cells) and cardiovascular risks (no hERG inhibition or aortic aneurysms in ApoE⁻/⁻ mice), distinguishing it from romosozumab, a clinically used anti-sclerostin antibody. For OA, SC-3 suppressed subchondral bone formation (via Runx2 and BMP-2 downregulation) and enhanced cartilage matrix synthesis (via Sox-9 and Col-II upregulation). In a rat OA model, weekly SC-3 intra-articular injections (50 µg/kg) for 8 weeks prevented OA progression and normalized bone volume. A single dose of SC-3 (50 µg/kg) delivered in a shear-thinning hydrogel matched multi-dose efficacy, addressing adherence challenges. This study identifies two distinct sclerostin-derived peptides: SC-1, a safe dual-action (anabolic and anti-catabolic) peptide for osteoporosis, and SC-3 for OA, with hydrogel-enabled sustained release enhancing its therapeutic potential.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118501"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922088","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":"Sclareol mitigates steatosis, inflammation, and fibrosis through the regulation of AMPK/SREBP1/NF-κB/TGF-β pathways in metabolic dysfunction-associated steatohepatitis","authors":"Poonam Yadav ,&nbsp;Sumeet Kumar Singh ,&nbsp;Ralf Weiskirchen ,&nbsp;Umashanker Navik","doi":"10.1016/j.biopha.2025.118512","DOIUrl":"10.1016/j.biopha.2025.118512","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). The increasing burden of MASH and its associated complications is challenging to cure. Our study aims to investigate the therapeutic potential of sclareol in MASH pathogenesis. Huh-7 cells were treated with various concentrations of free fatty acids (FFAs; 200–1200 µM), followed by treatment with sclareol (FFAs; 1200 µM + sclareol; 5 µM to 100 µM). An <em>in vivo</em> MASH model was developed using a high-fat diet and carbon tetrachloride (0.16 µg/kg every 15^th days) for 12 weeks, while control animals received a normal pellet diet. After model induction, animals were divided into four groups: Control, MASH, MASH + SLD (5 mg/kg/day, SLD: Sclareol low dose), and MASH + SHD (10 mg/kg/day, SHD: Sclareol high dose). Sclareol treatment was administered intraperitoneally for six weeks. In Huh-7 cells, co-treatment with sclareol, particularly at doses of 20, 40, and 80 µM, reduced reactive oxygen species and nitric oxide production while regulating lipogenic gene expression, thereby mitigating lipotoxicity. <em>In vivo</em>, sclareol alleviated dyslipidemia, hyperglycemia, liver injury, and oxidative stress in MASH animals. Histopathology confirmed that sclareol improved liver morphology by reducing nuclear infiltration, macro- and microsteatosis, hepatocyte ballooning, and fibrosis. GC-MS analysis revealed that sclareol intervention was associated with reduced fecal short-chain fatty acid (SCFA) levels. Interestingly, this reduction was accompanied by improvements in colon health. Furthermore, sclareol upregulated AMP-activated protein kinase and modulated the molecular expression of genes related to lipogenic, gluconeogenic, inflammation, fibrotic, and apoptotic pathways. This study is the first to report that sclareol prevents MASH progression by regulating oxidative stress, dyslipidemia, inflammation, fibrosis, and apoptosis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118512"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922087","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":"Carotenoids as neuroprotective agents in multiple sclerosis: Pathways, mechanisms, and clinical prospects","authors":"Elham Nadimi ,&nbsp;Shirin Jamal Omidi ,&nbsp;Mahshad Ghasemi ,&nbsp;Mohammad Hashem Hashempur ,&nbsp;Aida Iraji","doi":"10.1016/j.biopha.2025.118496","DOIUrl":"10.1016/j.biopha.2025.118496","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune and<!--> <!-->neurodegenerative disorder affecting the central nervous system (CNS), characterized by demyelination and neuroinflammatory responses, oxidative stress, and immune dysregulation. The global incidence of MS is rising, demonstrating the necessity for new therapeutic agents against its complex pathophysiology. Carotenoids, naturally pigments with strong antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective activities, have been recognized as promising candidates to target MS.The antioxidant effect of astaxanthin, lycopene, β-carotene, crocin, and lutein resulted from the deactivation of reactive oxygen species (ROS), preservation of mitochondrial integrity, and prevention of lipid peroxidation. Additionally, carotenoids regulate inflammatory pathways by suppressing NF-κB activation, reducing the expression of pro-inflammatory cytokines and activating the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf2) system. Carotenoids promote an immune balance that drives Th1/Th17 responses toward regulatory T cell (Treg)<!--> <!-->activity and reduces neuroinflammation and protecting oligodendrocytes necessary for the process of remyelination. Moreover, the role of phytochemicals in maintaining blood-brain barrier integrity and modulating gene expression provides evidence for their therapeutic potential.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118496"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932547","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":"From basics to clinics: New opportunities for metformin in tumor metabolic intervention and treatment","authors":"Huiying Lv ,&nbsp;Haofei Gong ,&nbsp;Ran Zhao ,&nbsp;Xuan Gao ,&nbsp;Wenyue Liu ,&nbsp;Lijun Zhao ,&nbsp;Ruili Sun","doi":"10.1016/j.biopha.2025.118507","DOIUrl":"10.1016/j.biopha.2025.118507","url":null,"abstract":"<div><div>Metformin, a cornerstone therapy for type 2 diabetes, has recently garnered attention for its multifaceted antitumor potential in cancer prevention and treatment. Emerging preclinical studies reveal that metformin suppresses tumor growth and metastasis through integrated mechanisms beyond singular metabolic pathways, while enhancing sensitivity to immunotherapy. Clinical evidence preliminarily supports its survival benefits and risk reduction in breast, colorectal, and hepatocellular carcinomas, particularly when combined with conventional or novel anticancer agents, demonstrating synergistic efficacy. Epidemiological and real-world data further highlight its preventive value in high-risk populations. Despite heterogeneity in therapeutic responses across cancer types and individuals, as well as unresolved challenges in long-term safety and acquired resistance, innovative drug delivery systems and precision oncology approaches are expanding its therapeutic boundaries. Bridging mechanistic insights with clinical translation, metformin is poised to emerge as a pivotal agent in metabolic-immunological synergy, offering novel paradigms for personalized cancer interception and therapy. This review systematically deciphers metformin’s pleiotropic mechanisms in cancer metabolism and anti-tumor immunity while critically evaluating its translational prospects, thereby illuminating new avenues for combinatorial metabolic-immunotherapeutic strategies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118507"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922079","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":"Molecular regulation and subtype-specific effects of naringenin and naringin on nicotinic acetylcholine receptors expressed in Xenopus oocytes","authors":"Jeongyeon Yun ,&nbsp;Myungmi Moon ,&nbsp;Jaehui Yang ,&nbsp;Hye Duck Yeom ,&nbsp;Mee-Hyun Lee ,&nbsp;Gihyun Lee ,&nbsp;Junho H. Lee","doi":"10.1016/j.biopha.2025.118494","DOIUrl":"10.1016/j.biopha.2025.118494","url":null,"abstract":"<div><div>Naringenin and naringin, bioactive flavonoids from citrus fruits, exhibit neuroprotective effects, showing promise for neurodegenerative diseases like Alzheimer's and Parkinson's. Additionally, they demonstrate significant anticancer potential, modulating key signaling pathways involved in tumor growth, apoptosis, and metastasis, thus expanding their therapeutic applications in cancer treatment. These compounds interact with nicotinic acetylcholine receptors (nAChRs), a class of ligand-gated ion channels critical for modulating neurotransmission within the central nervous system. In this study, naringenin and naringin were found to selectively inhibit specific subtypes of nAChRs in a concentration-dependent, reversible, and noncompetitive manner. These effects were examined using two-electrode voltage-clamp recordings in Xenopus laevis oocytes heterologously expressing various human nAChR subtypes, and further analyzed by site-directed mutagenesis and molecular docking simulations to identify key binding residues. Mutational analyses, supported by molecular docking, revealed that certain mutations in nAChRs eliminate naringin’s inhibitory effect, highlighting a selective binding affinity. This inhibition was observed selectively in α3β2 and α3β4 nAChR subtypes, which are significant within the autonomic nervous system, while α7 and α4β2 nAChRs, often implicated in neurodegenerative processes, remained unaffected. These findings suggest that naringenin and naringin could be developed as targeted modulators of nAChRs, offering therapeutic potential.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"191 ","pages":"Article 118494"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922172","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}