Phytomedicine最新文献

{"title":"Fufang Gaoziban Pian alleviates anxiety and depression-like behavior in mice via the gut-brain axis: Involvement of the estrogen signaling pathway","authors":"Wanting Ren ,&nbsp;Wenyue Yang ,&nbsp;Mengnan Zhou ,&nbsp;Shengquan Dai ,&nbsp;Yuqi Zhao ,&nbsp;Simeng Xu ,&nbsp;Xiaopeng Li ,&nbsp;Qiang Yin ,&nbsp;Hailong Yin ,&nbsp;Fei Song ,&nbsp;Xuebo Liu ,&nbsp;Danna Wang ,&nbsp;Beita Zhao","doi":"10.1016/j.phymed.2025.157268","DOIUrl":"10.1016/j.phymed.2025.157268","url":null,"abstract":"<div><h3>Background/Objective</h3><div>Fufang Gaoziban Pian (FGZBP) is a Uyghur patent Chinese medicine, and it has been shown to improve depressive symptoms. However, its impact on co-morbidity of anxiety and depression, as well as its exploration of the potential mechanisms, have not been probed in sufficient depth. This research explored the impacts of FGZBP on anxiety and depression-like behaviors, along with its underlying mechanisms in mice exposed to a stress model.</div></div><div><h3>Research design/Methodology</h3><div>In this study, mice with chronic unpredictable mild stress were treated with different doses of FGZBP. The ultrastructure of hippocampal synapses was assessed via transmission electron microscopy, and physiological changes in brain and intestinal tissues were evaluated using staining. Simultaneously, the modulatory effects of the FGZBP on brain and colonic transcriptions were assessed by RNA sequencing of brain and colon tissues, and potential mechanisms were explored. Additionally, inflammatory markers and candidate metabolites in serum and brain tissue were analyzed using RT-qPCR and ELISA, using 16 s rRNA sequence to test changes of intestinal microbiome.</div></div><div><h3>Results</h3><div>The results demonstrated that the high-dose FGZBP effectively alleviated depressive and anxious behaviors. It ameliorated brain histological and intestinal damage, upregulated the expression of genes linked with the estrogen receptor pathway in CUMS mice. Thereby reversing microglial activation, diminishing the secretion of pro-inflammatory mediators, and raising the expressions of BDNF and PSD-95, which was achieved by the high-dose FGZBP. Simultaneously, the high-dose FGZBP dysregulated the intestinal microecological disturbances and alleviated colonic oxidative stress and physiological changes induced by CUMS.</div></div><div><h3>Conclusion</h3><div>In summary, our findings suggested that the FGZBP reversed inflammation and oxidative stress in CUMS mice by regulating estrogen signaling pathways via the gut-brain axis, thereby reducing depressive and anxious behaviors.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157268"},"PeriodicalIF":8.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119739","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":"Mogroside V: Molecular mechanisms and therapeutic applications","authors":"Yun-Long He ,&nbsp;Pan Hu ,&nbsp;Hou-Lin Xia ,&nbsp;Yuan-Xiang Gong ,&nbsp;Wan-Ting Feng ,&nbsp;Li-Rong Deng ,&nbsp;Wen-Rong Li ,&nbsp;Yi-Jia Zeng","doi":"10.1016/j.phymed.2025.157250","DOIUrl":"10.1016/j.phymed.2025.157250","url":null,"abstract":"<div><h3>Background</h3><div>Mogroside V (MV) constitutes the primary bioactive compound within <em>Siraitia grosvenorii</em> and has significant therapeutic effects on oxidative stress, inflammation, osteoporosis, diabetes, obesity, and nervous system damage. Presently, there exists a shortage of comprehensive reviews explaining its therapeutic mechanisms through core signaling pathways.</div></div><div><h3>Aim</h3><div>To systematically organize and summarize recent advances MV's molecular mechanisms and its therapeutic potential.</div></div><div><h3>Methods</h3><div>The potential mechanisms of MV on the above diseases were explored by searching relevant literature published in databases such as PubMed, Web of Science, and Google Scholar, combined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.</div></div><div><h3>Results</h3><div>MV mediates its multifaceted biological functions via key signaling cascades. Anti-inflammatory actions are facilitated through pathways of Janus kinase/signal transducer and activator of transcription (JAK/STAT), Protein kinase B/ phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/Akt/mTOR), Toll-like receptor 4 (TLR4), and Endoplasmic reticulum stress (ERS)-unfolded protein response (ERS-UPR). For anti-oxidant defense, MV predominantly engages the Nuclear (factor erythroid 2-related factor 2/heme oxygenase 1) Nrf2/HO-1, PI3K/Akt, and sirtuin (SIRT) pathways. Furthermore, MV regulates metabolism and offers therapeutic potential by targeting the AMP-activated Protein Kinase (AMPK) pathway in obesity, modulating the PI3K/Akt/ glucose transporter type 2(GLUT2) axis for diabetes management, and activating the Taurine Upregulated Gene 1 (TUG1) pathway to enhance osteogenesis.</div></div><div><h3>Conclusions</h3><div>MV is a promising multi-target therapeutic candidate. Further studies on bioavailability optimization and clinical translation are warranted.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157250"},"PeriodicalIF":8.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107653","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":"Pseudostellaria heterophylla polysaccharides attenuate diabetic lower limb ischemia via CYP2E1-mediated mitochondrial homeostasis and PANoptosis regulation","authors":"Yiqiong Wang ,&nbsp;Yi Tao ,&nbsp;Shujing Zhang ,&nbsp;Qiuru Wang ,&nbsp;Zheting Liu ,&nbsp;Shudong Lin ,&nbsp;Yaoting Wang ,&nbsp;Yunchao Huang ,&nbsp;Ting Zhang ,&nbsp;Henry Anselmo Mayala ,&nbsp;Wenming He ,&nbsp;Hui Shen ,&nbsp;Ling Zhang ,&nbsp;Hui Chai","doi":"10.1016/j.phymed.2025.157252","DOIUrl":"10.1016/j.phymed.2025.157252","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) and its complications pose a significant threat to human health. Diabetes-related lower limb ischemia (DLLI), as a severe complication of diabetic macrovascular disease, presents substantial challenges in clinical management.</div></div><div><h3>Purpose</h3><div>The pharmacodynamic profile and mode of action of <em>Pseudostellaria heterophylla</em> polysaccharides (PHP) in DLLI treatment constitute the core investigative objectives herein.</div></div><div><h3>Study Design</h3><div>Using complementary in vivo (DLLI murine model) and in vitro (high glucose (HG)-exposed human umbilical vein endothelial cells (HUVECs)) systems, PHP's bioactivity was systematically profiled.</div></div><div><h3>Methods</h3><div>In vivo: The effects of PHP on blood perfusion, microvessel density, and PANoptosome assembly in the ischemic limbs of DLLI mice were evaluated.</div><div>In vitro: HUVECs treated with HG were used to assess PHP’s regulatory effects on angiogenesis functions (cell migration, proliferation, tube formation), PANoptosome/inflammasome formation, key components of the PANoptotic pathway, reactive oxygen species (ROS/mtROS), mitochondrial homeostasis, and autophagy. Transcriptomic analysis was conducted to identify potential target genes.</div></div><div><h3>Results</h3><div>In vivo: PHP significantly improved blood perfusion, increased microvessel density, and modulated PANoptosome assembly in ischemic limbs.</div><div>In vitro: PHP reversed HG-induced angiogenesis dysfunction, inhibited PANoptosis and oxidative stress, restored mitochondrial function, and enhanced autophagic activity.</div><div>Mechanism: PHP exerted its effects by targeting cytochrome P450 enzyme CYP2E1 through downregulating its expression, thereby alleviating mitochondrial damage and PANoptosis. Additionally, CYP2E1 downregulation promoted endothelial cell migration.</div></div><div><h3>Conclusion</h3><div>We pioneered a PANoptosome-centric framework for DLLI, proving that PHP target CYP2E1 to restore mitochondrial homeostasis, inhibit PANoptosis, and drive angiogenesis, thereby offering a novel natural product-derived therapeutic strategy. Collectively, this work establishes PHP as a promising candidate for DLLI treatment through CYP2E1-mediated restoration of mitochondrial homeostasis and PANoptosis suppression.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157252"},"PeriodicalIF":8.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159299","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":"Liquiritin in Chaihu-shugan-san alleviates Parkinson's Disease via PPARα-mediated inhibition of SCD1/FADS2-dependent Ferroptosis","authors":"Yawen Cai ,&nbsp;Guiqin Huang ,&nbsp;Chenxiao Shan ,&nbsp;Xiaohang Zhang ,&nbsp;LING YuYan ,&nbsp;Yu Fu ,&nbsp;Menghui Ren ,&nbsp;Tianhua Yan ,&nbsp;Min Xu ,&nbsp;Lingpeng Zhu","doi":"10.1016/j.phymed.2025.157262","DOIUrl":"10.1016/j.phymed.2025.157262","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing global prevalence. Chaihu-shugan-san (CSS) is a Chinese medicine compound with reported neuroprotective properties. However, the precise bioactive constituents and underlying mechanisms of CSS in the context of PD remain poorly defined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to systematically evaluate the therapeutic potential of CSS, characterize its bioactive constituents, and elucidate the potential molecular mechanisms in PD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A network pharmacology-bioinformatics framework was established to predict the potential targets of CSS in PD. MPTP-induced PD mouse models were validated by behavioral tests, histopathology (HE staining), immunohistochemistry (IHC), and Western blot (WB). Machine learning and ROC curve analysis pinpointed key ferroptosis-related genes linked to CSS and PD, with functional enrichment highlighting possible pathways. Further validation was performed using IHC, GPx, MDA, and WB assays. UPLC-MS/MS was employed to characterize bioactive CSS components, followed by druggability screening, molecular docking, and molecular dynamics (MD) simulations. &lt;em&gt;In vitro,&lt;/em&gt; MES23.5 cells exposed to MPP⁺ were used to evaluate the neuroprotective effects of &lt;em&gt;Liquiritin&lt;/em&gt; (LIQ), the principal active compound in CSS, via CCK-8, LDH, oxidative stress markers (GPx, MDA), lipid peroxidation (C11-BODIPY), iron accumulation (FerroOrange), and WB. Additional validation of ferroptosis modulation was performed &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Multidisciplinary investigations employing prediction and experimental validation consistently demonstrated the neuroprotective effects of CSS against MPTP-induced PD mouse. Machine learning, ROC curve analysis and &lt;em&gt;in vivo&lt;/em&gt; validation identified CSS ameliorates PD by inhibiting ferroptosis through PPARα activation. Intriguingly, CSS exhibited therapeutic potential by counteracting ferroptosis-triggered PD-like pathological manifestations in mice. Integrated analysis involving UPLC-MS/MS, druggability screening, molecular docking and MD simulations demonstrated LIQ to be a core bioactive compound in CSS. Mechanistic studies revealed that LIQ protects against MPP&lt;sup&gt;+&lt;/sup&gt;- or erastin-induced ferroptosis in MES23.5 cells via activation of the PPARα/SCD1/FADS2 pathway. Pharmacological inhibition of PPARα abolished LIQ's protective effects against both ferroptosis and PD progression, definitively establishing PPARα activation as essential for LIQ-mediated neuroprotection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;LIQ, a major bioactive component of CSS, ameliorates PD pathology by inhibiting ferroptosis through activation of the PPARα/SCD1/FADS2 signaling pathway. These findings uncover a novel anti-ferroptosis mechanism and provide a promising therapeutic framework for the prevention and tre","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157262"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119752","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":"Shexiang baoxin pill ameliorates cardiac fibrosis by inhibiting fibroblast to myofibroblast transition through STAT3 phosphorylation suppression","authors":"Xuan Xu ,&nbsp;Yanyi Tan ,&nbsp;Shengnan Li ,&nbsp;Min Zhong ,&nbsp;Zhigang Liu ,&nbsp;Jiayi Tong","doi":"10.1016/j.phymed.2025.157263","DOIUrl":"10.1016/j.phymed.2025.157263","url":null,"abstract":"<div><h3>Background</h3><div>Shexiang Baoxin Pill (SBP) is a traditional Chinese medicine used to treat ischemic cardiomyopathy. It can alleviate cardiac fibrosis following myocardial ischemia/reperfusion (MI/R) injury, but its action mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>To elucidate the mechanism by which SBP alleviates cardiac fibrosis.</div></div><div><h3>Methods</h3><div>snRNA-seq was employed to construct a cardiac cell atlas of MI/R mice treated with SBP, identify DEGs in fibroblasts, and analyse transcription factor activity. Molecular docking and molecular dynamics simulations were used to investigate the binding sites and binding stability of the screened SBP chemical components with the STAT3 protein. Immunohistochemistry, immunofluorescence, qRT-PCR and WB techniques were utilized to assess the impact of SBP treatment on cardiac fibrosis and myofibroblast transition, while echocardiography was used to evaluate cardiac function in mice.</div></div><div><h3>Results</h3><div>SBP treatment significantly improved cardiac function in mice subjected to MI/R injury: cardiac fibrosis area was reduced by 4.2 %, EF was increased by 4.5 % and FS was increased by 2.5 %. snRNA-seq revealed that SBP treatment did not alter the overall number of cardiac fibroblasts but modulated the proportional distribution of their subtypes. SCENIC-based transcription factor activity analysis suggested that the STAT3 signalling pathway might play a key role in this process. In vitro cell experiments demonstrated that H/R treatment induced the transition of fibroblasts into α-SMA-positive myofibroblasts, which SBP inhibited.</div></div><div><h3>Conclusions</h3><div>This study has demonstrated for the first time that SBP effectively attenuates cardiac fibrosis post-MI/R, and elucidated the mechanism by which SBP inhibits myofibroblast transdifferentiation via the STAT3 signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157263"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102855","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":"Epimedium brevicornu Maxim.-derived extracellular vesicle-like particles stimulate VEGF-mediated angiogenesis to alleviate postmenopausal osteoporosis","authors":"Xiuping Cai ,&nbsp;Tianxin Qiu ,&nbsp;Jiawen Shen ,&nbsp;Yukun Xu ,&nbsp;Zhengting Wu ,&nbsp;Jiehao Lin ,&nbsp;Hongguang Yang ,&nbsp;Qing Zhao ,&nbsp;Kewei Zhao","doi":"10.1016/j.phymed.2025.157259","DOIUrl":"10.1016/j.phymed.2025.157259","url":null,"abstract":"<div><h3>Background</h3><div>Postmenopausal osteoporosis (PMOP), a bone disease causing fragility fractures, affects millions of postmenopausal women. <em>Epimedium brevicornu Maxim.</em>(EP) shows anti-osteoporotic potential, but its active components and mechanisms remain unclear. <em>Epimedium brevicornu Maxim.</em>-derived extracellular vesicle-like particles (EP-EVLPs) are naturally occurring bioactive constituents. To date, no studies have comprehensively addressed the dual regulatory role of EP-EVLPs in PMOP.</div></div><div><h3>Purpose</h3><div>To investigate the bone-targeting capability and therapeutic efficacy of EP-EVLPs against PMOP.</div></div><div><h3>Methods</h3><div>EP-EVLPs were isolated from fresh EP leaves via differential ultracentrifugation and systematically characterized using transmission electron microscopy, nanoparticle tracking analysis, SDS-PAGE, agarose gel electrophoresis, thin-layer chromatography, and high-performance liquid chromatography. <em>In vivo</em> studies evaluated bone-targeting specificity, anti-osteoporotic activity, and biocompatibility in PMOP models. <em>In vitro</em> analyses included: 1) Osteogenic differentiation assessment of hBMSCs and MC3T3 cells through immunohistochemical staining and RT-qPCR; 2) HUVEC proliferation and apoptosis assays via CCK-8 and flow cytometry; 3) Angiogenic potential evaluation using bioinformatic analysis, wound healing, transwell migration, tube formation assays and ELISA.</div></div><div><h3>Results</h3><div>EP-EVLPs were isolated from <em>Epimedium brevicornu Maxim.</em> in the form of cup-shaped, bilayer nanoparticles, containing nucleic acids, proteins, lipids, epimedin C, and key anti-osteoporotic compounds (icariin). <em>In vivo</em> experiments revealed their preferential accumulation in osteoporotic femora, effectively mitigating bone loss without hepatorenal toxicity. Mechanistically, EP-EVLPs dose-dependently upregulated VEGF expression, enhancing HUVEC proliferation, migration, and tube formation. This angiogenesis-driven remodeling of the osseous vascular niche correlated with restored bone homeostasis.</div></div><div><h3>Conclusion</h3><div>We identify EP-EVLPs rescue postmenopausal osteoporosis through icariin-mediated activation of VEGF-driven angiogenesis. This plant-derived nano-platform restores bone homeostasis by revascularization-coupled osteogenesis, establishing a targeted therapeutic strategy with translational promise.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157259"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119753","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":"Synergistic inhibition of hepatocarcinogenesis by green alga Ulva lactuca polysaccharide and 5-fluorouracil targeted SERPINH1","authors":"Wei Liao ,&nbsp;Shuo Shan ,&nbsp;Jingxiang Xu ,&nbsp;Zhengxin Chen ,&nbsp;Yinfeng Wu ,&nbsp;Yuxi Wen ,&nbsp;Weichao Chen ,&nbsp;Chao Zhao","doi":"10.1016/j.phymed.2025.157266","DOIUrl":"10.1016/j.phymed.2025.157266","url":null,"abstract":"<div><h3>Background</h3><div>The serpin family H member 1 (SERPINH1) as a collagen-specific molecular chaperone, plays a crucial role in the biosynthesis of collagen. However, its function in hepatocellular carcinoma (HCC) is largely unexplored.</div></div><div><h3>Purpose</h3><div>To elucidate the mechanism which the combination of <em>Ulva lactuca</em> polysaccharide (ULP) and 5-fluorouracil (5-FU) synergistically inhibits tumors via targeting SERPINH1.</div></div><div><h3>Methods</h3><div>This study employed <em>in vitro</em> (RAW264.7 and HepG2 cells) and <em>in vivo</em> (H22 tumor-bearing mouse and xenograft zebrafish) models to investigate the mechanisms behind the synergistic antitumor effects and attenuated cytotoxicity of the ULP and 5-FU combination. RNA sequencing (RNA-seq) coupled with bioinformatic analyses was employed to explore the potential carcinogenesis and tumor-suppressive roles of SERPINH1. Furthermore, siRNA-mediated knockdown of SERPINH1 was performed to confirm its functional significance in HCC.</div></div><div><h3>Results</h3><div>A combination of ULP and 5-FU augments tumor cell inhibition and alleviates oxidative stress damage caused by chemotherapy. ULP and 5-FU inhibited collagen secretion by downregulating SERPINH1 expression, thereby impairing extracellular matrix (ECM) deposition. Consequently, this led to the suppression of invasion and migration in HepG2 cells.</div></div><div><h3>Conclusion</h3><div>ULP is identified as a novel natural agent that synergizes with 5-FU to suppress tumor progression, primarily by modulating the ECM. The combination treatment targets SERPINH1, inhibiting collagen-mediated ECM deposition and consequently reducing tumor cell migration and invasion.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157266"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092361","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":"Nordihydroguaiaretic acid (NDGA) exhibits potent anti-biofilm and antimicrobial activity against methicillin-resistant Staphylococcus aureus and Candida albicans","authors":"Xiangcheng Fan ,&nbsp;Chunyan Dai ,&nbsp;Jichun Han ,&nbsp;Shengying Lou ,&nbsp;Ningjun Zhang ,&nbsp;Minyang He ,&nbsp;Zhiqiang Zhu ,&nbsp;Peng Li ,&nbsp;Xingru Chen ,&nbsp;Xiaojun Xu","doi":"10.1016/j.phymed.2025.157265","DOIUrl":"10.1016/j.phymed.2025.157265","url":null,"abstract":"<div><h3>Introduction</h3><div>The global rise of antimicrobial resistance (AMR), particularly among biofilm-forming bacteria and fungi, has created an urgent need for novel therapeutics. Nordihydroguaiaretic acid (NDGA), a plant-derived polyphenolic lignan, has demonstrated promising biological activities, yet its potential as a dual-action antimicrobial agent remains underexplored.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the antimicrobial and anti-biofilm activities of NDGA against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>Candida albicans</em>, elucidate its mechanism of action, and assess its <em>in vivo</em> efficacy and biosafety.</div></div><div><h3>Materials and Methods</h3><div>NDGA’s antimicrobial activities were assessed through MIC, time-kill, and biofilm disruption assays against standard and clinical isolates. Transcriptomic profiling and deep-learning–guided molecular docking were used to identify key microbial targets and regulatory pathways. <em>In vivo</em> efficacy was validated in <em>Galleria mellonella</em> and murine systemic infection models. Cytotoxicity, hemolysis, and acute toxicity assays were conducted to evaluate biosafety.</div></div><div><h3>Results</h3><div>NDGA exhibited potent antimicrobial activity, with MIC values of 32 μg/ml for <em>S. aureus</em> USA300 and 64 μg/ml for <em>C. albicans</em> SC5314. It effectively eradicated persister cells and disrupting mature biofilms of both MRSA and <em>C. albicans</em>. Transcriptomic analysis revealed that NDGA modulated multiple microbial virulence and biofilm-regulating pathways, including arginine biosynthesis in MRSA and ergosterol metabolism in <em>C. albicans</em>. Docking studies confirmed strong binding affinity of NDGA to critical microbial targets. <em>In vivo</em>, NDGA significantly improved survival rates, reduced pathogen burden, and alleviated tissue damage, showing comparable efficacy to vancomycin and fluconazole. NDGA demonstrated favorable biosafety with low cytotoxicity, minimal hemolysis, and no observable acute toxicity in mammalian models.</div></div><div><h3>Conclusion</h3><div>NDGA is a promising antimicrobial candidate capable of disrupting biofilms and overcoming drug resistance in both bacterial and fungal infections. Its multitargeted mode of action, coupled with <em>in vivo</em> efficacy and biosafety, supports further development as a next-generation anti-infective agent.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157265"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102894","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":"Pathogenic mechanisms of cerebral ischemia and potential gut-brain axis-oriented therapeutic strategies","authors":"Chumeng Zhuang ,&nbsp;Qianqian Chen ,&nbsp;Xiaotong Dou ,&nbsp;Yangyang Zhang ,&nbsp;Weifeng Jin ,&nbsp;Xiahui Lu ,&nbsp;Haitong Wan ,&nbsp;Li Yu","doi":"10.1016/j.phymed.2025.157264","DOIUrl":"10.1016/j.phymed.2025.157264","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia is a serious cerebrovascular disease, and its pathogenesis is complex and involves a variety of pathological processes. In recent years, the theory of gut-brain axis has provided a new research perspective to reveal the synergistic pathological changes between brain and gut during cerebral ischemia. According to this theory, there is a bidirectional regulation mechanism between the central nervous system and gut microbiota, and the gut-brain axis plays a pivotal role in the occurrence and progression of cerebral ischemia. Therefore, drug intervention strategies based on gut-brain axis have gradually attracted attention. Existing studies have shown that, Chinese herbal medicines, compound prescriptions and Chinese patent medicines, can play potential therapeutic effects on cerebral ischemia by regulating intestinal flora, reducing neuroinflammation and oxidative stress. Despite the continuous progress of related research in recent years, the understanding of the role of gut-brain axis in cerebral ischemia is still patchy and lack of systematic summary.</div></div><div><h3>Purpose</h3><div>This article reviews the pathogenesis of cerebral ischemia regulated by the gut-brain axis and frontier drug intervention research based on this theory, in order to provide reference for follow-up research and clinical practice.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157264"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092402","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":"Combined transcriptomics and network pharmacology to elucidate the mechanisms of rutin in treating ischemic stroke rat","authors":"Ting Zheng ,&nbsp;Taotao Jiang ,&nbsp;Yufeng Chen ,&nbsp;Jianqing Xie ,&nbsp;Weiyuan Yu ,&nbsp;Manxia Wang","doi":"10.1016/j.phymed.2025.157267","DOIUrl":"10.1016/j.phymed.2025.157267","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) is a neurovascular disorder characterized by a prolonged treatment period and a high risk of recurrence. Rutin, a principal flavonol, has demonstrated potential neuroprotective effects in previous studies; however, its regulatory mechanism on neuroinflammation following IS remains incompletely elucidated.</div></div><div><h3>Purpose</h3><div>This investigation aims to elucidate the neuroprotective mechanisms of rutin in IS, with a particular focus on the NF-κB/NLRP3 signaling pathway.:</div></div><div><h3>Methods</h3><div>A dual investigative strategy was employed, combining a transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia model in vivo with oxygen-glucose deprivation and reoxygenation (OGD/R)-treated astrocyte cultures in vitro. These experimental approaches were integrated with network pharmacology prediction and transcriptomic profiling to systematically elucidate the neuroprotective efficacy and multitarget regulatory mechanisms of rutin.</div></div><div><h3>Results</h3><div>Our research demonstrated that rutin significantly reduces infarct volume and improves neurological outcomes in the tMCAO rat model, with the most pronounced effects occurring at a dosage of 80 mg/kg. Network pharmacological research analysis identified 91 putative rutin targets associated with IS, including key inflammatory mediators such as interleukin – 6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β. After rutin intervention, the levels of nuclear factor kappa-B (NF-κB) p65, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, IL-1β, IL-18, IL-6, and TNF-α were significantly reduced, while Gastermin D (GMDSD) was increased in tMCAO rats. In the OGD/R model, rutin inhibited the activation of NLRP3, and further enhanced the inhibition of NF-κB in combination with JSH-23.</div></div><div><h3>Conclusions</h3><div>This study delineates a multimodal neuroprotective efficacy of rutin in IS, mechanistically characterized by its coordinated suppression of the neuroinflammation-pyroptosis axis via NF-κB/NLRP3 pathway modulation. The dose-dependent attenuation of astrocytic homeostasis disruption further substantiates its therapeutic precision, consistent with the multitarget engagement patterns predicted by network pharmacology. Notably, functional validation with an NLRP3 agonist highlights pathway specificity, positioning rutin as a promising phytochemical scaffold for the development of neurovascular unit-stabilizing agents. These findings not only broaden the pharmacodynamic paradigm of flavonoid-based stroke therapeutics but also advocate for systematic exploration of rutin's translational potential in modulating neuroinflammatory cascades across neurological disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157267"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102889","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}