Biomedicine & Pharmacotherapy最新文献

{"title":"Chronic citalopram effects on the brain neurochemical profile and perfusion in a rat model of depression detected by the NMR techniques – spectroscopy and perfusion","authors":"Iveta Harastova-Pavlova ,&nbsp;Eva Drazanova ,&nbsp;Lucie Kratka ,&nbsp;Petra Amchova ,&nbsp;Maria Hrickova ,&nbsp;Ondrej Macicek ,&nbsp;Jiri Vitous ,&nbsp;Radovan Jirik ,&nbsp;Jana Ruda-Kucerova","doi":"10.1016/j.biopha.2024.117656","DOIUrl":"10.1016/j.biopha.2024.117656","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (¹H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable <em>in vivo</em> markers of the pathological processes underlying MDD.</div></div><div><h3>Methods</h3><div>This study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. ¹H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions.</div></div><div><h3>Results</h3><div>The ¹H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model–citalopram treatment interaction was observed using ¹H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group.</div></div><div><h3>Conclusion</h3><div>Collectively, ¹H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117656"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study on physicochemical characterization and immunomodulatory activities of neutral and acidic Lycium barbarum polysaccharides","authors":"Jia-Lun Duan ,&nbsp;Meng-Qiu Liu ,&nbsp;Ya-Nan Liu ,&nbsp;Xiao-Fei Liang ,&nbsp;Cheng Cao ,&nbsp;An-Ni Yao ,&nbsp;Li-Qiang Zhao ,&nbsp;Sheng Guo ,&nbsp;Da-Wei Qian ,&nbsp;Chun-Jie Bao ,&nbsp;Ming Zhao ,&nbsp;Jin-Ao Duan","doi":"10.1016/j.biopha.2024.117659","DOIUrl":"10.1016/j.biopha.2024.117659","url":null,"abstract":"<div><div><em>Lycium barbarum</em> polysaccharides (LBPs) are recognized as key bioactive constituents of <em>Lycium barbarum</em> with diverse biological activities. However, current research on LBPs is largely confined to crude extracts, offering limited insight into the structural properties underlying their biological effects. In this study, we separated crude LBP into acidic LBP (ALBP) and neutral LBP (NLBP), which exhibited distinct physicochemical properties. ALBP, consisting of 76.18 % galacturonic acid (GalA), demonstrated crystallinity, thermal stability and gelatinous characteristics. In contrast, NLBP, with only 3.16 % GalA, displayed a more porous structure and superior fluidity. Furthermore, functional analysis revealed that NLBP exhibited enhanced immunoregulatory effects by activating dendritic cells and repolarizing macrophages. In a B16F10 melanoma-bearing C57BL/6 J mice model, NLBP significantly inhibited tumor growth with an inhibition rate of 66.7 % through macrophage repolarization. The findings highlight the distinct biological effects of NLBP and ALBP, providing a theoretical foundation for the refined utilization of LBP.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117659"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic evidence of black soybean ethanolic extract and 2-aminobutyric acid in suppressing neuroinflammation and enhancing synaptic transmission","authors":"Sharmin Aktar ,&nbsp;Ayumi Kato ,&nbsp;Kyoko Toda ,&nbsp;Shinya Takahashi ,&nbsp;Mari Maeda-Yamamoto ,&nbsp;Farhana Ferdousi ,&nbsp;Hiroko Isoda","doi":"10.1016/j.biopha.2024.117633","DOIUrl":"10.1016/j.biopha.2024.117633","url":null,"abstract":"<div><h3>Introduction</h3><div>Recently, the awareness of the beneficial utilization of natural bioactive compounds in treating neuroinflammation has gained particular attention. We aimed to understand the anti-neuroinflammatory effect of black soybeans (<em>Glycine max</em> (L.) Merr) ethanolic extract (BBEE) and its bioactive compound, 2-aminobutyric acid (2-AB), against LPS-induced SH-SY5Y cells.</div></div><div><h3>Method</h3><div>Cell viability and the optimum therapeutic dose were confirmed by MTT assay. We conducted a whole-transcriptomic analysis of BBEE and 2-AB in LPS-induced SH-SY5Y cells using microarray normalized with SST-RMA. DEGs were selected based on p-value &lt; 0.05 and fold change &gt; 2, and validated by RT-qPCR and immunocytochemical analyses.</div></div><div><h3>Results</h3><div>We found that both BBEE and 2-AB down-regulated the expression of inflammatory cytokines <em>IL6 and TNFA</em> under LPS-induced conditions. This was also observed in the microarray data, showing downregulation of several inflammatory pathways, such as NF-kB, and IL6-JAK/STAT3-signaling pathways. In contrast, it upregulated the expression of <em>CALML3, GRIN2,</em> and <em>GRIA2</em> gene expressions, which influence the AMPK and CAMK2 signaling pathways, indicating the potential of BBEE in neurotransmission and synaptic function. Also, immunofluorescence analysis revealed that 2-AB treatment significantly increased PSD-95 and Ca²⁺ levels, suggesting its effect on synaptic transmission essential for brain function.</div></div><div><h3>Conclusion</h3><div>Our findings suggest the potential anti-neuroinflammatory effects of BBEE and 2-AB, which may offer therapeutic and preventive benefits in mitigating neurological disorders. Given that BB is widely consumed in many Asian countries, our study may encourage its incorporation into the daily diet to slow inflammation-induced neurodegenerative disorders, reduce age-related cognitive decline, and enhance overall brain function.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117633"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gas immnuo-nanomedicines fight cancers","authors":"Mengchi Sun ,&nbsp;Tianye Wang ,&nbsp;Yinmei Zhu ,&nbsp;Feng Ling ,&nbsp;Jingwen Bai ,&nbsp;Chengwu Tang","doi":"10.1016/j.biopha.2024.117595","DOIUrl":"10.1016/j.biopha.2024.117595","url":null,"abstract":"<div><div>Certain gas molecules, including hydrogen (H₂), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), oxygen (O₂) and sulfur dioxide (SO₂) exhibit significant biological functionalities that can modulate the immune response. Strategies pertaining to gas-based immune therapy have garnered considerable attention in recent years. Nevertheless, delivering various gas molecules precisely into tumors, which leads to enhanced anti-tumor immunotherapeutic effect, is still a main challenge. The advent of gas treatment modality with desirable immunotherapeutic efficiency has been made possible by the rapid development of nanotechnology, which even derives the concept of the gas immnuo-nanomedicines (GINMs). In light of the fact, we herein aim to furnish a cutting-edge review on the latest progress of GINMs. The underlying mechanisms of action for several gases utilized in cancer immunotherapy are initially outlined. Additionally, it provides a succinct overview of the current clinical landscape of gas therapy, and introduces GINMs specifically designed for cancer treatment based on immunotherapeutic principles across multiple strategies. Last but not least, we address the challenges and opportunities associated with GINMs, exploring the potential future developments and clinical applications of this innovative approach.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117595"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of Coix lachrymal L. seed extract on the expression of inflammation and fibrogenesis genes in human retinal pigment epithelial cells","authors":"Zahra Gharegezloo ,&nbsp;Zahra Rezvani ,&nbsp;Fatemeh Sanie-Jahromi ,&nbsp;Foroogh Namjoyan","doi":"10.1016/j.biopha.2024.117646","DOIUrl":"10.1016/j.biopha.2024.117646","url":null,"abstract":"<div><div>Proliferative vitreoretinopathy (PVR) is a vision-threatening condition associated with retinal-detachment (RD), primarily caused by fibrocellular scar membrane formation. This study investigates the therapeutic potential of adlay seed extract fractions in mitigating PVR-associated pathways, focusing on oxidative stress, proliferation, inflammation, and fibrogenesis in retinal pigment epithelial (RPE) cells. Adlay seed extract fractions (methanolic: MeOH and residual: Res) were obtained through solvent extraction and characterized for carbohydrate, protein, flavonoid content, and antioxidant activity. RPE cells were cultured, and their viability in response to adlay fractions was assessed using the MTT assay. Gene expression analysis of IL-1β, IL-6, LIF, TGF-β, Snail and α-SMA genes was conducted via real-time PCR after treatment with adlay fractions. The Res fraction exhibited higher levels of protein, carbohydrate, flavonoids, and phenols compared to the MeOH fraction, along with significantly enhanced antioxidant activity. Both fractions showed inhibitory effects on RPE cell viability, with the Res fraction demonstrating a more pronounced impact. Gene expression analysis revealed a significant decrease in IL-6 and TGF-β expression with the MeOH fraction treatment, while the Res fraction led to decreased expression of IL-6, LIF, TGF-β, Snail and α-SMA, indicating a more comprehensive modulation of PVR-associated pathways. This study highlights the potential therapeutic benefits of adlay seed extract fractions in mitigating PVR-associated pathways in RPE cells. The Res fraction, particularly rich in bioactive compounds and exhibiting potent antioxidant activity, shows promise in attenuating oxidative stress, proliferation, inflammation, and fibrogenesis, critical processes in PVR development. These findings underscore the potential of adlay seed extracts as a novel therapeutic strategy for PVR warranting further investigation and clinical validation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117646"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title: Systematic insights into cell density-dependent transcriptional responses upon medium replacements","authors":"Pol Pérez-Rubio ,&nbsp;Elianet Lorenzo Romero ,&nbsp;Laura Cervera ,&nbsp;Francesc Gòdia ,&nbsp;Lars Keld Nielsen ,&nbsp;Jesús Lavado-García","doi":"10.1016/j.biopha.2024.117640","DOIUrl":"10.1016/j.biopha.2024.117640","url":null,"abstract":"<div><div>Understanding the molecular mechanisms governing transfection efficiency and particle secretion in high cell density cultures is critical to overcome the cell density effect upon transient gene expression. The effect of different conditioned media in HEK293 transcriptome at low and high cell density is explored. A systematic pair-wise comparative study was performed to shed light on the effect on previous phenotypical characteristics of different media conditions: fresh, exhausted and media depleted from extracellular vesicles (EVs) as well as associated proteins and RNAs. The obtained results suggest that restorative effects observed in transfection efficiency when employing EV-depleted media may arise predominantly from physicochemical alterations rather than cellular processes. A significant downregulation of genes associated with nucleocytoplasmic transport for the conditions involving the use of exhausted or EV-depleted media was observed. Moreover, upregulation of histone-related genes in EV-depleted media suggest a role for histone signaling in response to cellular stress or growth limitations, thereby highlighting the potential of manipulating histone levels as a promising strategy to enhance transient transfection. It was also corroborated that the accumulation of extracellular matrix proteins upon cell growth may inhibit transfection by an already-known competitive effect between cell membrane-bound and free proteoglycans. Proteomic characterization of EV-depleted media further unveiled enrichment of pathways associated with infection response and double-strand DNA breaks, suggesting that HEK293 cells undergo an induced infection-like state that disrupts cellular processes. Importantly, the study reveals that EV-depleted media stimulates virion release pathways underscoring the complex interplay between extracellular vesicles and viral budding.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117640"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquo-ethanolic extract of Lilii Bulbus attenuates dexamethasone-induced muscle loss and enhances muscle strength in experimental mice","authors":"Aeyung Kim ,&nbsp;Jinhee Kim ,&nbsp;Bu-Yeo Kim ,&nbsp;Chang-Seob Seo ,&nbsp;Yu Ri Kim ,&nbsp;Kwang Hoon Song ,&nbsp;No Soo Kim","doi":"10.1016/j.biopha.2024.117658","DOIUrl":"10.1016/j.biopha.2024.117658","url":null,"abstract":"<div><div>Traditionally, <em>Lilium lancifolium</em> bulb is known for its ability to nourish yin, nourish the lungs, clear the heart, soothe coughs, reduce irritability, and calm the mind. In Oriental Medicine, it is categorized as a tonic remedy for alleviating symptoms of fatigue and enhancing the strength of bones and muscles.</div><div>In this study, we aimed to validate the effectiveness of the aquo-ethanolic extract of Lilli Bulbus (LBE) in a dexamethasone (DEX)-induced muscle atrophy model, both <em>in vitro</em> and <em>in vivo</em>, and elucidate its mechanism of action through muscle transcriptome analysis. The effects of LBE on the viability and myotube density of C2C12 myoblasts and differentiated C2C12 myotubes with and without DEX treatment were investigated. LBE pretreatment protected C2C12 myoblast cells and increased the muscle density of C2C12 myotubes in response to DEX. LBE showed potent free radical scavenging activities in cell-free biochemical assays as well as antioxidant activity in C2C12 myoblasts. LBE also exhibited protective effects in an experimental animal model of DEX-induced muscle atrophy, showing muscular function and motor coordination recovery. Transcriptomic analysis of three different muscle tissues from mice with DEX-induced muscle atrophy showed that the regulation of the extracellular matrix was perturbed by glucocorticoid treatment, and this perturbation was reversed by LBE treatment.</div><div>Collectively, LBE alleviated skeletal muscle loss and maintained muscle function from the chronic toxicity of DEX by protecting muscle cells from various stressful conditions, as well as DEX itself, inhibiting muscle protein degradation, and preserving the muscle tissue microenvironment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117658"},"PeriodicalIF":6.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and mechanism of extracellular traps in chronic rhinosinusitis","authors":"Jiani Li ,&nbsp;He Zhao ,&nbsp;Jing Yang ,&nbsp;Meng Wang ,&nbsp;Zhiwei Cao ,&nbsp;Yunxiu Wang ,&nbsp;Zhaowei Gu","doi":"10.1016/j.biopha.2024.117655","DOIUrl":"10.1016/j.biopha.2024.117655","url":null,"abstract":"<div><div>Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nose that affects millions of individuals worldwide. Recent research has introduced the concept of an immunologic endotype based on the pathological characteristics of CRS and the types of inflammatory cell infiltration. This endotype concept is conducive to understanding CRS pathology and guiding further targeted therapy. Eosinophils and neutrophils infiltrate different proportions in different CRS endotypes and release extracellular traps (ETs) as a response to the extracellular immune response. The mechanisms of formation and biological roles of ETs are complex. ETs can trap extracellular microorganisms and limit the range of inflammation to some extent; however, excessive and long-term ETs may be related to disease severity. This review summarises and explores the mechanism of ETs and the advances in CRS research and proposes new insights into the interaction between ETs and programmed cell death (including autophagy, pyroptosis, and necroptosis) in CRS, providing new ideas for the targeted therapy of CRS.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117655"},"PeriodicalIF":6.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bioactive extracts from Eucalyptus globulus leaves in experimental models of Alzheimer’s disease","authors":"Patrícia Moreira ,&nbsp;Jéssica Macedo ,&nbsp;Patrícia Matos ,&nbsp;Joana Bicker ,&nbsp;Ana Fortuna ,&nbsp;Artur Figueirinha ,&nbsp;Lígia Salgueiro ,&nbsp;Maria Teresa Batista ,&nbsp;Ana Silva ,&nbsp;Sónia Silva ,&nbsp;Rosa Resende ,&nbsp;Pedro Costa Branco ,&nbsp;Maria Teresa Cruz ,&nbsp;Cláudia Fragão Pereira","doi":"10.1016/j.biopha.2024.117652","DOIUrl":"10.1016/j.biopha.2024.117652","url":null,"abstract":"<div><div>Current therapies for Alzheimer’s disease (AD) do not delay its progression, therefore, novel disease-modifying strategies are urgently needed. Recently, an increasing number of compounds from natural origin with protective properties against AD have been identified. Mixtures or extracts obtained from natural products containing several bioactive compounds have multifunctional properties and have drawn the attention because multiple AD pathways can be simultaneously modulated. This study evaluated the <em>in vitro</em> and <em>in vivo</em> effect of the essential oil (EO) obtained from the hydrodistillation of <em>Eucalyptus globulus</em> leaves, and an extract obtained from the hydrodistillation residual water (HRW). It was observed that EO and HRW have anti-inflammatory effect in brain immune cells modeling AD, namely lipopolysaccharide (LPS)- and amyloid-beta (Aβ)-stimulated microglia. In cell models that mimic AD-related neuronal dysfunction, HRW attenuated Aβ secretion and Aβ-induced mitochondrial dysfunction. Since the HRW’s major components did not cross the blood-brain barrier, both EO and HRW were administered to the APP/PS1 transgenic AD mouse model by an intranasal route, which reduced cortical and hippocampal Aβ levels, and to rescue memory deficits and anxiety-like behaviors. Finally, HRW and EO were found to regulate cholesterol levels in aged mice after intranasal administration, suggesting that these extracts can reduce hypercholesterolemia and avoid risk for AD development. Overall, findings support a protective role of <em>E. globulus</em> extracts against AD‑like pathology and cognitive impairment highlighting the underlying mechanisms. These extracts obtained from underused forest biomass could be useful to develop nutraceutical supplements helpful to avoid AD risk and to prevent its progression.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117652"},"PeriodicalIF":6.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Citrus flavonoids diosmin, myricetin and neohesperidin as inhibitors of Pseudomonas aeruginosa: Evidence from antibiofilm, gene expression and in vivo analysis","authors":"Tamara Carević ,&nbsp;Stoimir Kolarević ,&nbsp;Margareta Kračun Kolarević ,&nbsp;Nataša Nestorović ,&nbsp;Katarina Novović ,&nbsp;Biljana Nikolić ,&nbsp;Marija Ivanov","doi":"10.1016/j.biopha.2024.117642","DOIUrl":"10.1016/j.biopha.2024.117642","url":null,"abstract":"<div><div>Citrus flavonoids are group of bioactive polyphenols. Here, we investigated the potential of diosmin, myricetin and neohesperidin as possible inhibitors of <em>Pseudomonas aeruginosa</em>. This bacterium is a major clinical challenge due to its propensity to form resistant biofilm. The aims of this study were to examine flavonoids antibacterial activity using the microdilution method, assays intended to determine several antibiofilm mechanisms (crystal violet, congo red binding, extracellular DNA (eDNA) test and confocal laser scanning microscopy (CLSM) live/dead cell imaging), followed by virulence genes RT-qPCR analysis. Furthermore, we aimed to examine <em>in vivo</em> toxicity of the compounds as well as their efficacy in <em>P. aeruginosa</em> zebrafish embryo infection model. Minimal inhibitory concentrations of tested flavonoids towards <em>P. aeruginosa</em> were in range 0.05 – 0.4 mg/mL. A high potential of the compounds to disturb both the formation of the bacterial biofilm and its eradication was recorded, including significant reduction in biofilm biomass, exopolysaccharide and eDNA production. Biofilm treatment with diosmin resulted in the lowest percentage of live microbial cells as observed in the CLSM live/dead cell imaging. The <em>lasI</em>, <em>pvdS</em>, and <em>rhlC</em> genes were found to be downregulated in the presence of diosmin and myricetin. Only diosmin stood out as non-embryotoxic. Consequently, <em>in vivo</em> analysis using a zebrafish model of <em>P. aeruginosa</em> infection showed an antivirulence effect of diosmin. Our findings suggest that diosmin could be potential candidate for the development of new agent that target <em>P. aeruginosa</em> infections by reducing its virulence mechanisms.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117642"},"PeriodicalIF":6.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}