Biomedicine & Pharmacotherapy最新文献

{"title":"Corrigendum to “Bone marrow mesenchymal stem cell exosome-derived lncRNA TUC339 influences the progression of osteoarthritis by regulating synovial macrophage polarization and chondrocyte apoptosis“ [Biomed. Pharmacother. 167 (2023) 115488]","authors":"Xun Shen , Jian Qin , Zijian Wei , Feng Liu","doi":"10.1016/j.biopha.2025.118152","DOIUrl":"10.1016/j.biopha.2025.118152","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118152"},"PeriodicalIF":6.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070705","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":"Doxycycline: An essential tool for Alzheimer’s disease","authors":"Gianluigi Forloni","doi":"10.1016/j.biopha.2025.118159","DOIUrl":"10.1016/j.biopha.2025.118159","url":null,"abstract":"<div><div>The identification of active interventions in neurodegenerative disorders is a major challenge in neurology; the use of repurposed drugs may represent a valuable strategy. Tetracyclines, a second generation of antibiotic molecules, offer various potential applications. Following an anecdotal observation of the potential anti-amyloidogenic activity of iododoxorubicin, the search for chemical analogs with a better safety profile led to tetracyclines. Their heterocyclic structures with a planar conformation interfere with b-sheet amyloid formation. Thus, doxycycline, a derivative with favorable blood-brain barrier penetration, emerged as a strong candidate to combat peripheral and central amyloidosis. In particular, we tested the anti-prion activity of doxycycline <em>in vitro</em> and <em>in vivo</em> experiments, confirming its capacity to disrupt or inhibit the formation of prion protein aggregates associated with pathological events. Treatment with doxycycline in human subjects with prion - related encephalopathies yielded contradictory results, suggesting that a preventive approach is a more favorable condition to verify efficacy; a clinical trial involving subjects at genetic risk of developing fatal familial insomnia, exposed to doxycycline for ten years, is currently ongoing. The anti-amyloidogenic capacity of doxycycline, combined with its safety profile in long-term treatment, has suggested its use in peripheral amyloidosis, which was tested with positive results. A specific interaction with β-amyloid or α-synuclein oligomers, as well as tau aggregation has also been demonstrated. More recently, the action of doxycycline has been extended to its anti-inflammatory and antioxidant capacities. In particular, the anti-inflammatory activity of doxycycline may explain the drug 's efficacy in numerous experimental models where protein misfolding has been associated with neuroinflammation, including Huntington's and Parkinson' s diseases. Thus, the pleiotropic action of doxycycline appears to be an interesting tool for addressing progressive neuronal dysfunction in multifactorial neurodegenerative diseases. The application of precision medicine principles to doxycycline treatment represents the best strategy to determine its efficacy. These aspects are illustrated here concerning another pleiotropic tetracycline, minocycline.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118159"},"PeriodicalIF":6.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941630","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":"Design, development and evaluation of a tritium-labeled radiotracer for ecto-5’-nucleotidase (CD73) – A versatile research tool and diagnostic agent for personalized medicine","authors":"Riham M. Idris ,&nbsp;Haneen Al-Hroub ,&nbsp;Constanze C. Schmies ,&nbsp;Patrick Riziki ,&nbsp;Christian Renn ,&nbsp;Tobias Claff ,&nbsp;Katharina Sylvester ,&nbsp;Susanne Moschütz ,&nbsp;Julia Reinhardt ,&nbsp;Winnie Deuter-Conrad ,&nbsp;Jennifer M. Dietrich ,&nbsp;Marieta Toma ,&nbsp;Bernd K. Fleischmann ,&nbsp;Daniela Wenzel ,&nbsp;Herbert Zimmermann ,&nbsp;Michael Hölzel ,&nbsp;Norbert Sträter ,&nbsp;Christa E. Müller","doi":"10.1016/j.biopha.2025.118115","DOIUrl":"10.1016/j.biopha.2025.118115","url":null,"abstract":"<div><div>Ecto-5’-nucleotidase (CD73) is the main enzyme that catalyzes the hydrolysis of extracellular AMP to produce anti-inflammatory, immunosuppressive adenosine. Many tumor cells over-express ectonucleotidases accumulating adenosine in the tumor microenvironment, which promotes tumor growth, metastasis, angiogenesis, and immune escape. CD73 is upregulated in inflammation, and possesses potential as a biomarker and as a novel drug target for inflammatory diseases and cancer immunotherapy. New, metabolically stable <em>N</em>⁶-disubstituted adenosine-5’-diphosphate analogs were synthesized providing a basis for the design and preparation of the CD73-selective radioligand [³H]PSB-17230 by catalytic hydrogenation of a propargyl-substituted precursor. It showed high, pico- to low nanomolar affinity for human, rat and mouse CD73, slow dissociation kinetics, negligible non-specific binding, and high selectivity, as confirmed by studies on an inactive CD73 mutant and CD73 knockout cells. A high-resolution co-crystal structure (2.35 Å) of PSB-17230 with human CD73 elucidated its binding interactions. Radioligand binding was employed to characterize competitive CD73 inhibitors and to study expression levels of the enzyme in tissues and tumor cell lines of different species. Moreover, [³H]PSB-17230 was employed in autoradiography studies to determine CD73 expression in healthy and diseased mouse and human tissues. Significant upregulation of CD73 was observed in a mouse asthma model and in kidney cancer biopsies as compared to healthy controls. [³H]PSB-17230 represents a high-affinity tracer which is anticipated to find broad application in drug screening, preclinical studies, and for diagnostic purposes in inflammation and cancer, enabling drug monitoring and targeted therapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118115"},"PeriodicalIF":6.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937147","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":"Polyphyllin I induces ferritinophagy dependent ferroptosis through EZH2 and promotes anti-tumor immunity","authors":"Mengfei Xu ,&nbsp;Xiaoyan Yu ,&nbsp;Luyu Jia ,&nbsp;Mingnan Ye ,&nbsp;Yueyang Zhao ,&nbsp;Rui Wang ,&nbsp;Qing Tang ,&nbsp;Gangxing Zhu ,&nbsp;Jicai Chen ,&nbsp;Qichun Zhou ,&nbsp;Shigui Deng ,&nbsp;Sumei Wang","doi":"10.1016/j.biopha.2025.118165","DOIUrl":"10.1016/j.biopha.2025.118165","url":null,"abstract":"<div><h3>Background</h3><div>Polyphyllin I (PPI), the primary active component extracted from the commonly utilized drug <em>Paris polyphylla</em>, in clinical applications, exhibits exceptional anti-tumor activity. Therefore, the objective of this study is to delve into its antitumor properties by promoting ferroptosis and enhancing anti-tumor immunity.</div></div><div><h3>Results</h3><div>Our result demonstrate that PPI effectively suppresses the proliferation of NSCLC cells and triggers their demise through the induction of ferroptosis. Furthermore, the degradation of iron via autophagy is pivotal in mediating PPI-induced ferroptosis in NSCLC. Notably, EZH2 emerges as a potential key target of PPI, and its overexpression can significantly attenuate the therapeutic efficacy of PPI. Lastly, these mechanistic insights and pathways were corroborated in animal model, and we preliminarily revealing a stimulatory role of PPI in bolstering anti-tumor immunity.</div></div><div><h3>Conclusion</h3><div>PPI triggers ferroptosis in NSCLC by downregulating EZH2, promoting NCOA4/Ferritin mediated ferritinophagy, and enhances anti-tumor immunity by promoting CD8 +T infiltration into tumor tissue.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118165"},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942119","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":"Daidzein effectively mitigates amyloid-β-induced damage in SH-SY5Y neuroblastoma cells and C6 glioma cells","authors":"Alp Yiğit Özdemir ,&nbsp;Esin Akbay Çetin ,&nbsp;Jiří Novotný ,&nbsp;Vladimír Rudajev","doi":"10.1016/j.biopha.2025.118157","DOIUrl":"10.1016/j.biopha.2025.118157","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most debilitating form of dementia, characterized by amyloid-β (Aβ)-related toxic mechanisms such as oxidative stress, neuroinflammation, and mitochondrial dysfunction. The development of AD is influenced by environmental factors linked to lifestyle, including physical and mental inactivity, diet, and smoking, all of which have been associated with the severity of the disease and Aβ-related pathology. In this study, we used differentiated SH-SY5Y neuroblastoma and C6 glioma cells to investigate the neuroprotective and anti-inflammatory effects of daidzein, a naturally occurring isoflavone, in the context of Aβ oligomer-related toxicity. We observed that pre-treatment with daidzein prevented Aβ-induced cell viability loss, increased oxidative stress, and mitochondrial membrane potential decline in both SH-SY5Y and C6 cells. Furthermore, daidzein application reduced elevated levels of MAPK pathway proteins, pro-inflammatory molecules (cyclooxygenase-2 and IL-1β), and pyroptosis markers, including caspase-1 and gasdermin D, all of which were increased by Aβ exposure. These findings strongly suggest that daidzein alleviates inflammation and toxicity caused by Aβ oligomers. Our results indicate that daidzein could be a potential therapeutic agent for AD and other Aβ-related neurodegenerative diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118157"},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942118","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":"Obesity-related drug-metabolizing enzyme expression alterations in the human liver","authors":"Katarzyna Kosicka-Noworzyń ,&nbsp;Aleksandra Romaniuk-Drapała ,&nbsp;Yi-Hua Sheng ,&nbsp;Christine Yohn ,&nbsp;Luigi Brunetti ,&nbsp;Leonid Kagan","doi":"10.1016/j.biopha.2025.118155","DOIUrl":"10.1016/j.biopha.2025.118155","url":null,"abstract":"<div><h3>Objective</h3><div>Implications of obesity extend beyond the association with various health conditions, impacting physiological changes that affect the liver and the activity of metabolizing enzymes. Given the prevalence of obesity and the risk for drug-drug interactions owing to the comorbidity burden, the current drug dosage recommendations may need reevaluation for patients with obesity. This study evaluated the implications of obesity on the gene expression of hepatic drug-metabolizing enzymes. As drug clearance is an essential pharmacokinetic parameter for maintaining drug dosing regimens, investigating alterations in metabolizing enzymes expression is a critical step.</div></div><div><h3>Methods</h3><div>Human liver samples were collected post-mortem from 32 individuals and classified into the control (18.5 ≤ BMI &lt;25 kg/m²; range 18.9–24.4 kg/m²; median 2².3 kg/m²) and the study group (BMI ≥25 kg/m²; range 25.1–55.5 kg/m²; median 31.2 kg/m²). Real-time quantitative PCR was performed for the analysis of 168 drug-metabolizing enzymes.</div></div><div><h3>Results</h3><div>Our studies revealed several potential physiologically relevant differences, but the statistical significance was reached only for <em>ALDH3B1</em>, <em>PTGS1</em>, and <em>CEL</em> (all being up-regulated in the study group).</div></div><div><h3>Conclusions</h3><div>The study adds to our understanding of the mechanisms of pharmacokinetic changes in overweight and obesity. The findings require further exploration on the protein level, through proteomic and functional studies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118155"},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942016","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":"Fucoxanthin supplemented combinatorial treatment accelerates diabetic wound healing in rats by targeting hypermethylation of Ang-1 promoter via DNMT-1 inhibition","authors":"Kaarthik Saravanan,&nbsp;Reena Rajkumari Baskaran","doi":"10.1016/j.biopha.2025.118148","DOIUrl":"10.1016/j.biopha.2025.118148","url":null,"abstract":"<div><div>It has been widely established that DNA methyl transferase 1 has a role in the epigenetic regulation of numerous complications including diabetes and inhibition of the same is widely being seen as a potential therapeutic mechanism to treat these complications. Fucoxanthin is a carotenoid that has widely been reported to have a wealth of biological functions. Fucoxanthin is believed to be involved in a broad spectrum of pathways to produce anti-cancer, anti-obesity and antioxidant effects. In this study, fucoxanthin was encapsulated within myristic acid and BSA particles. These particles were tested for their physicochemical properties and fucoxanthin encapsulated within these particles exhibited superior thermal and storage stability. In-vitro digestion tests were carried out further confirming the ability of the encapsulation process to enhance the biological activity of fucoxanthin. The efficacy of fucoxanthin encapsulated particles were evaluated at in-vivo level using diabetic wound models in wistar rats. Fucoxanthin when delivered as an oral supplement in combination with linseed polysaccharide gel as wound dressing managed to significantly accelerate wound healing progression when compared with control and treatment groups. Fucoxanthin when delivered orally also managed to significantly inhibit DNA methyl transferase 1 leading to Angiopoietin 1 upregulation eventually resulting in accelerated wound healing.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118148"},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942116","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":"Effects of maternal drinking patterns and epigallocatechin-3-gallate treatment on behavioural and molecular outcomes in a mouse model of fetal alcohol spectrum disorders","authors":"Melina Vieiros ,&nbsp;Laura Almeida-Toledano ,&nbsp;Mariona Serra-Delgado ,&nbsp;Elisabet Navarro-Tapia ,&nbsp;Anna Ramos-Triguero ,&nbsp;Concha Muñoz-Lozano ,&nbsp;Leopoldo Martínez ,&nbsp;Emilia Marchei ,&nbsp;María D. Gómez-Roig ,&nbsp;Óscar García Algar ,&nbsp;Vicente Andreu-Fernández","doi":"10.1016/j.biopha.2025.118138","DOIUrl":"10.1016/j.biopha.2025.118138","url":null,"abstract":"<div><div>Prenatal alcohol exposure (PAE) impairs fetal development leading to fetal alcohol spectrum disorders (FASD). Antioxidants like epigallocatechin-3-gallate (EGCG) may mitigate alcohol-induced oxidative stress, a major contributor to FASD. This study assessed the effects of PAE on cognition and behaviour under two drinking patterns and the role of postnatal EGCG therapy in a FASD-like mouse model. C57BL/6J mice were divided into five groups: control, moderate drinking (Mod), binge drinking (Bin), Mod+EGCG, and Bin+EGCG. Cognitive and behavioural performance were assessed using Rotarod test, T-Maze, and Morris Water Maze (MWM). Western blot analyses evaluated brain and cerebellum biomarkers related to neuronal plasticity, maturation, differentiation, transport, and proliferation. PAE impaired motor coordination, significantly reducing rotarod walking time in both drinking patterns. Spatial learning and memory were also disrupted, decreasing T-maze success rate. It also decreased time in the platform area and distance travelled in MWM. Both drinking patterns affected neuronal plasticity (BDNF, DYRK1A) and maturation (NeuN), astrocyte differentiation (GFAP, s100β), neuronal transport (MBP) and proliferation (GDNF, Wnt-3) via oxidative stress (Nrf2). Our results show how EGCG treatment significantly improved behavioural tests results and restored most brain and cerebellum biomarkers, reaching levels similar to control. These findings highlight the impact of PAE on cognition and behaviour and how EGCG may counteract its effects by reducing oxidative stress and enhancing brain plasticity. Our findings open the door to future studies on the mechanism of action of this antioxidant in order to use it as a therapeutic tool in this vulnerable population.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118138"},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929243","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":"Pharmacological modulation of neutrophils, in contrast to that of macrophages/microglia, is sex independent and delays the development of morphine tolerance in a mouse model of neuropathic pain","authors":"Katarzyna Pawlik ,&nbsp;Katarzyna Ciapała ,&nbsp;Agata Ciechanowska ,&nbsp;Wioletta Makuch ,&nbsp;Joanna Mika","doi":"10.1016/j.biopha.2025.118149","DOIUrl":"10.1016/j.biopha.2025.118149","url":null,"abstract":"<div><div>Identifying sex-specific mechanisms underlying neuropathic pain, as well as its therapy, remains a challenge. Recent studies suggest important roles for neutrophils, macrophages and microglia in the development of hypersensitivity and the morphine effectiveness. Therefore, the aim of this study was to test whether substances that inhibit the activation/influx of neutrophils (4-aminobenzoic hydrazide) and microglia/macrophages (minocycline) can help achieve pain relief in male/female mice and improve the analgesic effectiveness of morphine in neuropathy in both sexes. Our behavioral studies performed using chronic constriction injury of the sciatic nerve indicate that repeated twice-daily administrations of 4-aminobenzoic hydrazide (in both sexes) and minocycline (only in males) cause analgesia and delay morphine tolerance development. Observations in female include the absence of alleviation of tactile hypersensitivity (von Frey test) following minocycline, and even an increase in thermal hypersensitivity (cold plate test), which may be of clinical importance. This may be explained by a lack of impact on IBA-1 protein level after repeated administration of minocycline in females, along with increased levels of pronociceptive factors such as CCL2, CXCL2, and TNFα. Notably, the repeated twice-daily administration of 4-aminobenzoic hydrazide has beneficial analgesic effects and delays morphine tolerance development in both sexes. Its influence on male mice is likely caused by its impact on spinal neutrophil activation/influx and on the level of anti-(IL-4)/pro-(CCL2) nociceptive cytokines. Our studies provide the first evidence that the inhibition of neutrophil activation/influx during long-term morphine treatment can improve its efficacy and delay the development of opioid tolerance in neuropathy in both sexes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118149"},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929242","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":"Methylene blue as a potential intervention in sepsis: Effects on survival and microcirculation in rat models of sepsis","authors":"Fabiola Mestriner ,&nbsp;Pedro Brüch Dantas ,&nbsp;Jessyca Michelon-Barbosa ,&nbsp;Vinicius Flora Dugaich ,&nbsp;Fabio Luis-Silva ,&nbsp;Mauricio S. Ribeiro ,&nbsp;Paulo R. Evora ,&nbsp;Christiane Becari","doi":"10.1016/j.biopha.2025.118131","DOIUrl":"10.1016/j.biopha.2025.118131","url":null,"abstract":"<div><div>Sepsis is a life-threatening condition characterized by systemic inflammation and microcirculatory dysfunction. Methylene blue (MB), a compound with known antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study aimed to investigate the effects of MB on survival rates and the preservation of mesenteric microcirculation in a rat model of endotoxemia. A total of 36 rats underwent cecal ligation and puncture (CLP) surgery to induce varying degrees of sepsis: mild (4 perforations), moderate (10 perforations), and severe (20 perforations). Animals received intravenous treatment with either MB (4 mg/kg) or saline. Survival was monitored for ten days. Additionally, intravital microscopy was used to assess leukocyte rolling and adhesion in mesenteric vessels following lipopolysaccharide (LPS)-induced sepsis. The experimental groups included saline, LPS + saline, MB + saline, LPS + MB, and MB + LPS. MB treatment significantly improved survival in the severe sepsis group, with a 30 % survival rate at ten days (p = 0.02, 95 % CI: 0.12–0.48), whereas all animals in the severe sepsis + saline group died within nine days. No significant survival benefit was observed in the mild and moderate sepsis groups (mild sepsis: p = 0.45, 95 % CI: 0.08–0.34; moderate sepsis: p = 0.32, 95 % CI: 0.15–0.51). In the LPS-induced model, treatment with both LPS and MB significantly reduced leukocyte rolling and adhesion (p &lt; 0.001, 95 % CI: 0.45–0.75 for rolling; p &lt; 0.03, 95 % CI: 0.30–0.60 for adhesion), with values comparable to those of the control group. In contrast, MB alone had no effect on leukocyte rolling or adhesion.In summary, MB significantly improved survival in severe sepsis and inhibited leukocyte migration in mesenteric vessels. These findings suggest that MB may protect the microcirculation and enhance survival under severe septic conditions, representing a promising therapeutic approach for sepsis management.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118131"},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929337","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}