Phytomedicine最新文献

{"title":"Bacopaside I, acting as an aquaporin 1 inhibitor, ameliorates rheumatoid arthritis via suppressing aquaporin 1-mediated autophagy.","authors":"Yan Huang, Meng-Yuan Zhou, Ling-Ling Li, Min Lv, Ze-Shan Xu, Xin-Jie Wu, Sheng-Long Gu, Man-Yu Zhang, Li Cai, Rong Li","doi":"10.1016/j.phymed.2025.156444","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156444","url":null,"abstract":"<p><strong>Background: </strong>Aquaporin 1 (AQP1) is a promising target for regulating fibroblast-like synoviocyte (FLS) behaviors in rheumatoid arthritis (RA). Bacopaside I (BSI), the main active compound of the herbal medicine Bacopa monnieri with anti-RA effects, inhibits tumor cell growth by blocking AQP1, but its potential use in RA is unclear.</p><p><strong>Purpose: </strong>To address BSI's anti-RA effects and elucidate its underlying mechanisms.</p><p><strong>Methods: </strong>We investigated BSI's therapeutic effects on TNF-α-induced RA FLS and identified AQP1 as its direct target through molecular docking, cellular thermal shift assay (CETSA), and AQP1 knockdown experiments. We studied BSI's impacts on rat adjuvant-induced arthritis (AIA) and synovial proliferation, apoptosis, and autophagy in AIA rat synovium. We explored the role of autophagy inhibition in BSI's effects in vitro and in vivo by co-treating with the autophagy activator rapamycin (Rapa) and/or the inhibitor 3-methyladenine (3-MA).</p><p><strong>Results: </strong>BSI suppressed proliferation, promoted apoptosis, and reduced autophagy in TNF-α-stimulated RA FLS. Notably, BSI's in vitro effects were reduced by Rapa and enhanced by 3-MA. The molecular docking and CETSA confirmed BSI's binding to AQP1, while AQP1 knockdown invalidated BSI's in vitro effects, further indicating AQP1 as the target of BSI. In vivo, BSI attenuated the severity of rat AIA, alongside reduced synovial proliferation, increased apoptosis, and decreased autophagy within AIA rat synovium. Moreover, Rapa co-treatment negated BSI's effects on synovial proliferation and apoptosis and abolished its anti-AIA activity.</p><p><strong>Conclusions: </strong>BSI, as an AQP1 inhibitor, hindered AQP1-mediated autophagy, causing increased apoptosis, reduced proliferation in RA FLS, and relieved rat AIA symptoms.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156444"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis reveals QiShenYiQi Pills ameliorates ischemia-induced heart failure through inhibition of mitochondrial fission.","authors":"Jia Li, Xinyao Zhang, Liuqing Hou, Bo-Yu Liu, Yuan-Ming Fan, Yajun Zhang, Feizuo Wang, Keke Jia, Xiang Li, Zongxiang Tang, Xiaojian Yin","doi":"10.1016/j.phymed.2025.156435","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156435","url":null,"abstract":"<p><strong>Background: </strong>QiShenYiQi Pills (QSYQ) has widely used in clinical treatment of cardiovascular diseases; however, the exact mechanism behind its effectiveness still requires further investigation.</p><p><strong>Purpose: </strong>The purpose of the study was to explore the potential mechanism of QSYQ in the treatment of ischemic heart failure from the perspective of proteomics.</p><p><strong>Methods: </strong>In vivo, to observe QSYQ actions on the progression of ischemia-induced heart failure, cardiac function and remodeling was analyzed. The heart tissues of mice were used for Tandem Mass Tag (TMT)-based proteomic analysis. Cardiomyocytes were prepared and subjected to oxygen-glucose deprivation injury. QSYQ effects on differential proteins expressions, mitochondrial fission and mitochondrial function were assayed.</p><p><strong>Results: </strong>QSYQ treatment preserved cardiac function, limited cardiac fibrosis and alleviated cardiomyocyte hypertrophy in post-myocardial ischemia mice. Proteomic analysis revealed that QSYQ-responsive proteins were mainly involved in mitochondrial fission, including mitochondrial calcium uniporter (MCU), membrane associated ring-CH-type finger 5 (MARCHF5), and mitochondrial fission process 1 (MTFP1). Protein-protein interaction analysis revealed that MCU, MARCHF5 and MTFP1 commonly interacted with dynamin-related protein 1 (DRP1). Knockdown of MCU, MARCHF5, or MTFP1 attenuated excessive mitochondrial fission in cardiomyocytes through regulating DRP1 phosphorylation and its mitochondrial translocation. QSYQ decreased the phosphorylation of DRP1 at Ser616 and enhanced its inhibitory phosphorylation at Ser637, as well as mitigating the mitochondrial recruitment and oligomerization of DRP1, through downregulation of these three differential proteins. As a result, QSYQ alleviated aberrant mitochondrial fission, ameliorated mitochondrial dysfunction, and protected cardiomyocytes from ischemic injury.</p><p><strong>Conclusion: </strong>The novelty lies in the proteomics-based investigation of the mechanism of QSYQ, uncovering that QSYQ mitigated ischemia-induced heart failure by suppressing MCU/MARCHF5/MTFP1-DRP1-driven mitochondrial fission.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156435"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zhuyu pill attenuates metabolic-associated fatty liver disease by regulating macrophage polarization through TLR4 signaling pathway.","authors":"Mei Zhao, Qingman He, Xinyao Shu, Ruitong Xu, Zhongyi Zhang, Yu Mou, Wenhao Liao, Yong Zhang, Zubing Zhou, Tao Shen","doi":"10.1016/j.phymed.2025.156439","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156439","url":null,"abstract":"<p><strong>Background: </strong>Metabolic-associated fatty liver disease (MAFLD) is the leading chronic liver disease globally, impacting a large segment of the population. The Zhuyu Pill (ZYP), a traditional Chinese remedy, has been clinically used for treating MAFLD, with its effectiveness demonstrated in both human patients and animal models. However, the underlying mechanisms of how ZYP addresses MAFLD still require further investigation.</p><p><strong>Objective: </strong>This study investigated the molecular mechanism of ZYP in treating MAFLD through both in vivo and vitro methods.</p><p><strong>Methods: </strong>A murine MAFLD model was induced by a high-fat, high-fructose diet for 12 weeks. ZYP was administered for 4 weeks, with fenofibrate serving as a positive control. Indicators of lipid metabolism in serum and liver tissue were detected by automatic biochemical analyzer and ELISA, respectively. Histopathological evaluation of liver sections was performed using HE and oil red O staining. Transcriptomics was employed to further investigate the therapeutic mechanism of ZYP in MAFLD. Additionally, macrophages and their polarization in the liver were analyzed using ELISA, flow cytometry, immunohistochemistry, and immunofluorescence (IF). Candidate proteins and pathways were validated in vivo and in vitro by western blotting and IF. Validation of the pathway was performed in vitro using inhibitors and co-culture strategies.</p><p><strong>Results: </strong>ZYP significantly improved obesity and hepatic steatosis in MAFLD mice, reducing body/liver weight and regulating lipid metabolism indicators in serum and liver tissue. Bioinformatics analysis of transcriptomic data highlighted lipid metabolism regulation and inflammation control as key effects of ZYP in treating MAFLD. The in vivo experimental results showed that ZYP inhibited M1 polarization of macrophages (pro-inflammatory) and promoted M2 polarization of macrophages (anti-inflammatory) in MAFLD mice. Further in vivo and vitro experiments indicated that ZYP competes with LPS to bind to Toll-like receptor 4 (TLR4), suppressing M1 polarization in liver macrophages, and improving MAFLD. The in vitro co-culture system also confirmed that ZYP reduces liver lipid deposition by modulating M1 macrophage polarization.</p><p><strong>Conclusions: </strong>ZYP alleviates MAFLD by inhibiting M1 polarization of liver macrophages, indicating that ZYP may be a promising treatment for MAFLD. Its mechanism of action is to inhibit the TLR4/MyD88/TRAF6 signaling pathway, modulate macrophage polarization, and improve inflammatory response.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156439"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Jiawei Buzhong Yiqi Decoction attenuates polycystic ovary syndrome through regulating kisspeptin-GPR54-AKT-SHBG system\" [Phytomedicine 133C (2024) 155931 Online ahead of print].","authors":"Runan Hu, Yuli Geng, Yanjing Huang, Zhuo Liu, Fan Li, Kunkun Song, Wenwen Ma, Haoxu Dong, Mingmin Zhang, Ting Lei, Yufan Song, Zhuo Zhang","doi":"10.1016/j.phymed.2025.156415","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156415","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156415"},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zyxin-a novel detrimental target, is inhibited by Saikosaponin A during allergic asthma.","authors":"Haoyun Bai, Yongjing Zhang, Xinping Zhang, Chenjia Li, Mengyang Ma, Jie Gao, Tingting Deng, Chang Gao, Nan Wang","doi":"10.1016/j.phymed.2025.156434","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156434","url":null,"abstract":"<p><strong>Background: </strong>Allergic asthma is a heterogeneous disease involving numerous inflammatory cells. Mast cell (MC) plays a key role during allergic asthma. Saikosaponin A (SSA) inhibits MC activation and ameliorates allergic asthma, however, its underlying mechanism remains unclear. This study aims to identify SSA-binding proteins and reveal their functions.</p><p><strong>Methods: </strong>C57BL/6J mice were used to establish allergic asthma models to evaluate therapeutic effect of SSA. Protein microarray, RNA-seq, surface plasmon resonance (SPR), and pull-down assay were used to explore and validate the binding proteins of SSA. The functions of Zyxin were explored by knockdown and overexpression in LAD2. Zyxin knockout mice were constructed to investigate the role of Zyxin in allergic asthma.</p><p><strong>Results: </strong>SSA alleviates allergic asthma and inhibits MC activation. Zyxin was confirmed as a binding protein of SSA. In vitro experiments proved the crucial role of Zyxin in mast cell exocytosis. Zyxin Ser142/143 is phosphorylated during MC activation, which can be inhibited by SSA. In vivo studies showed that Zyxin expression in MC has detrimental effects, while its deficiency ameliorates allergic asthma.</p><p><strong>Conclusion: </strong>Our results verified the detrimental effect of Zyxin in allergic asthma for the first time. We also innovatively demonstrated that SSA exerts inhibitory effects on MC activation and allergic asthma by directly binding to and inhibiting Zyxin phosphorylation.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156434"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening effective-component compatibility from Jinshui Chenfei formula for silicosis treatment by serum-pharmacochemistry and feedback system control.","authors":"Xinguang Liu, Peng Zhao, Liming Wang, Jinyan Wu, Wenrui He, Yu Wei, Hongrui Chen, Jiansheng Li","doi":"10.1016/j.phymed.2025.156419","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156419","url":null,"abstract":"<p><strong>Background: </strong>The unclear chemical composition and mechanisms of action pose challenges for new drug development and quality control of traditional Chinese medicine (TCM) formulas. To address this, the concept of effective-component compatibility (ECC) was proposed to represent drug combination with equivalent efficacy to TCM formulas, along with clear composition and dosage. However, previous strategies for screening ECC have often overlooked the synergistic effects of its components.</p><p><strong>Purpose: </strong>This study proposed a strategy integrating serum pharmacochemistry and feedback system control (FSC) to identify synergistic combinations as ECC of TCM formulas. The strategy was applied to identify the ECC of Jinshui Chenfei formula (JCF) for silicosis treatment.</p><p><strong>Methods: </strong>A chemical library of JCF was constructed using ultra-high-performance liquid chromatography-quadrupole extractive orbitrap mass spectrometry (UHPLC-Q-Extractive Orbitrap MS). The library was then used to identify absorbed prototype compounds of JCF, and the serum levels of its main components were analyzed. Based on the primary absorbed prototypes, FSC was employed to screen the most effective synergistic combinations from JCF for inhibiting LPS- and IL-4-induced macrophage polarization. The pharmacological effects of ECC-JCF were further validated using a silica-induced silicosis mouse model, and its synergistic mechanisms were investigated through transcriptomics and molecular dynamic simulations.</p><p><strong>Results: </strong>A total of 437 compounds were identified in JCF, with 203 absorbed prototypes detected following oral administration. After three rounds of FSC iterative screening, a synergistic combination of isoliquiritin (180 μg/ml/0.43 mM), glycyrrhizic acid (180 μg/ml/0.22 mM), and gallic acid (3.75 μg/ml/0.02 mM) significantly inhibited the expression of TNF-α, IL-1β, IL-6, CD206, and Arg-1 mRNA in mouse alveolar macrophages. This combination also protected lung tissues from alveolar collapse, inflammatory cell infiltration, fibroblast proliferation, and fibrous nodule formation. In addition, the combination improved alveolitis and fibrosis scores in silicosis mice, outperforming both the original JCF formula and the sum of individual components. The synergistic effects of these compounds may regulate targets in inflammation and fibrosis formation pathways.</p><p><strong>Conclusion: </strong>This study identified an ECC of JCF with a well-defined composition and mechanism of action, facilitating the future development of JCF as a new drug. Compared with traditional ECC screening methods, this strategy reduces experimental workload while accounting for synergistic effects.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156419"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Z-Ligustilide Alleviates Atherosclerosis by Reconstructing Gut Microbiota and Sustaining Gut Barrier Integrity through Activation of Cannabinoid Receptor 2\" [Phytomedicine. 135(2024)156117].","authors":"Si-Jing Liu, Jiao-Jiao Fu, Zhen-Yue Liao, Yi-Xin Liu, Jing He, Li-Ying He, Jing Bai, Jing-Yan Yang, Shu-Qi Niu, Jin-Lin Guo","doi":"10.1016/j.phymed.2025.156414","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156414","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156414"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dahuang chuanxiong decoction against contrast-induced nephropathy: Multi-omics, crosstalk between BNIP3-mediated mitophagy and IL-17 pathway.","authors":"Zhiyong Song, Jun Li, Xuezhong Gong","doi":"10.1016/j.phymed.2025.156416","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156416","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Contrast-induced nephropathy (CIN), also known as contrast-induced acute kidney injury (CI-AKI), represents a prevalent form of hospital-acquired renal injury. However, the mechanisms underlying its pathogenesis remain unclear. Based on our previous research findings, the Dahuang Chuanxiong decoction (DCH), composed of Radix et Rhizoma Rhei (DH) and Rhizoma Chuanxiong (CX), has demonstrated efficacy for inhibiting CI-AKI by attenuating oxidative stress and apoptosis in renal tubular epithelial cells. Despite these findings, the detailed mechanisms underlying the renoprotective actions have not been thoroughly clarified.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;The objective of this study was to screen potential targets and signaling pathways involved in inhibition of CI-AKI by DCH using multi-omics analysis and to verify whether the renoprotective mechanism of DCH is related to these identified targets or pathways through in vivo and in vitro experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Initially, we identified the components of DCH using UPLC-Q-TOF-MS. Transcriptomics and proteomics, combined with experimental validation, were used to further elucidate the molecular mechanisms of the herbal pair in CI-AKI treatment. A CI-AKI rat model was established, and the expression levels of proteins related to mitophagy and the IL-17 signaling pathway were detected in renal tissues using immunofluorescence, immunohistochemistry, and western blotting analysis to elucidate the nephroprotective effects of DCH. Additionally, siRNA was used in the HK-2 cell model to investigate the crosstalk between the mitophagy and IL-17 signaling pathways and the impact on apoptosis when these pathways were inhibited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multi-omics results revealed that the crucial signaling pathways involved were mitophagy, the MAPK signaling pathway, and the IL-17 signaling pathway. In vivo experiments indicated that contrast media (CM) led to an increase in AKI biomarkers, with upregulated expression of Parkin, BNIP3, IL-17, and p-NF-κB. Notably, pretreatment with DCH markedly reversed the expression of these proteins. Furthermore, we confirmed the importance of IL-17-mediated inflammation in the pathogenesis of CIN in vitro. We stimulated HK-2 cells with human IL-17 recombinant protein and observed an increase in the expression of p-NF-κB. Conversely, knockdown of IL-17 receptor A (IL-17RA) on the cell membrane reduced the expression of p-NF-κB and BNIP-3 under IL-17 stimulation. Additionally, the results revealed that BNIP3 knockdown reduced p-NF-κB production and alleviated the inflammation triggered by CM. The crosstalk between the two signaling pathways was initially explored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In conclusion, these findings suggested that DCH may exert ameliorative effects on CI-AKI through a multifaceted approach, including inhibition of BNIP3-mediated mitophagy and IL-17-mediated inflammation. This study elucidat","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156416"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting membrane integrity and imidazoleglycerol-phosphate dehydratase: Sanguinarine multifaceted approach against Staphylococcus aureus biofilms.","authors":"Qianwei Qu, Xingyu Huang, Zhenxin Zhu, Jun Wang, Mengmeng Zhao, Wenqiang Cui, Yadan Zheng, Yanyan Liu, Xueying Chen, Zhiyun Zhang, Na Dong, Chunliu Dong, Yanhua Li","doi":"10.1016/j.phymed.2025.156428","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156428","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti-S. aureus effect. Nevertheless, the specific mechanism of action of sanguinarine against S. aureus biofilms remains unexplored.</p><p><strong>Purpose: </strong>The objective of this study was to elucidate the target site of sanguinarine in S. aureus, as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics.</p><p><strong>Methods: </strong>Initially, we assessed the in vitro anti-S. aureus properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with S. aureus biofilm formation was preliminarily analyzed in vitro. Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated in vivo using mouse models of biofilm and bacteremia.</p><p><strong>Results: </strong>Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering S. aureus biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the S. aureus load in mouse organs and the formation of biofilm on the surface of implants in vivo without any resistance.</p><p><strong>Conclusions: </strong>In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of S. aureus and targeting IGPD. These findings suggest that sanguinarine holds potential for further development as a novel antibiotic to combat biofilm-associated infections.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156428"},"PeriodicalIF":6.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting pyroptosis: A novel strategy of ginseng for the treatment of diabetes and its chronic complications.","authors":"Ke Li, Ya-Jun Wang, Chen Chen, Xiao-Jie Wang, Wei Li","doi":"10.1016/j.phymed.2025.156430","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156430","url":null,"abstract":"<p><strong>Background: </strong>Pyroptosis is a recently identified form of programmed cell death that plays a crucial role in the pathogenesis and progression of diabetes and associated chronic complications, while the occurrence mechanism remains unclear. Ginseng (Panax Ginseng C. A. Mey.) is a valuable traditional medicinal material with proved therapeutic effects on prevention and treatment of diabetes and diabetic complications. Targeting pyroptosis pathway has become a focus of study for ginseng in improvement of diabetes and related chronic complications.</p><p><strong>Purpose: </strong>The review aims to elucidate the happening mechanism of pyroptosis in diabetes and diabetic chronic complications, evaluate the effects of ginseng and its active components on diabetes and its chronic complications via pyroptosis-related pathways, and provide a new perspective for the management of diabetes.</p><p><strong>Methods: </strong>We conducted the literature retrieval with PubMed, Web of Science, and ScienceDirect databases in a systematic manner (up to August 2024). The keywords included pyroptosis, diabetes, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic neuropathy, ginseng, ginseng extract, and ginsenoside. The obtained literatures were comprehensively sorted out.</p><p><strong>Results: </strong>Oxidative stress, endoplasmic reticulum stress (ERS), and inflammatory responses were primary contributors to pyroptosis in diabetes and associated chronic complications. In addition, some RNA molecules (miRNAs, circRNAs, and lncRNAs) also contributed to pyroptosis under hyperglycemia. The signaling pathways mainly included Nrf2/HO-1, IκB/NF-κB/NLRP3, NOX1/NOX4/TXNIP, and P2X7R/TXNIP/NLRP3. Ginseng extracts, some ginsenosides and flavonoid (Quercetin) could exert anti-diabetic effect by regulating pyroptosis-related pathways. We also discussed the toxicity, side effects and clinical applications of ginseng.</p><p><strong>Conclusion: </strong>In summary, this review elucidates the happening mechanisms of pyroptosis in diabetes and associated chronic complications, and summarizes published studies about ginseng and its active ingredients in improving diabetes by regulating pyroptosis-related pathways. However, almost all researches are limited to animal and cell experiments, and more clinical trials are required to prove the therapeutic effect of ginseng on diabetes by targeting pyroptosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"156430"},"PeriodicalIF":6.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}