Phytomedicine最新文献

{"title":"Xin-Ji-Er-Kang modulates NRF2 to inhibit ferroptosis and attenuate doxorubicin-induced myocardial injury.","authors":"Si-Min Yang, Zhang-le Hu, Hui-Yu Jia, Pang-Bo Yang, Zhi-Wei Xu, Cong Ma, Sheng-Yong Luo, Wei Chen, Shan Gao","doi":"10.1016/j.phymed.2025.157302","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157302","url":null,"abstract":"<p><strong>Background: </strong>Xin-Ji-Er-Kang (XJEK), a traditional Chinese medicine formulation, has shown protective effects in various murine models of cardiovascular disease. However, its potential mechanisms in mitigating drug-induced cardiotoxicity, particularly its role in regulating ferroptosis, remain unclear.</p><p><strong>Aim of the study: </strong>This study aimed to evaluate the cardioprotective effects of XJEK against doxorubicin (DOX)-induced myocardial injury and to elucidate its potential mechanisms.</p><p><strong>Materials and methods: </strong>The protective effects of XJEK were assessed using in vivo and in vitro models of DOX-induced cardiotoxicity (DIC). Cardiac function, related biomarkers, mitochondrial function, and indicators of ferroptosis were evaluated. To clarify the mechanism, NRF2 expression was silenced using small interfering RNA (siRNA).</p><p><strong>Results: </strong>XJEK significantly alleviated DIC both in vivo and in vitro by restoring mitochondrial function, reducing lipid peroxidation, lowering reactive oxygen species (ROS) production, and decreasing iron accumulation and ferroptosis-related protein expression. Mechanistically, XJEK exerted these protective effects by inhibiting ferroptosis through activation of the NRF2 pathway.</p><p><strong>Conclusion: </strong>XJEK effectively attenuates DOX-induced cardiotoxicity by suppressing ferroptosis via NRF2 activation. These findings suggest that NRF2-mediated anti-ferroptosis signalling contributes to the cardioprotective effects of XJEK, highlighting its therapeutic potential for managing drug-induced myocardial injury.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157302"},"PeriodicalIF":8.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244684","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":"Liuwei Dihuang formula ameliorates perimenopausal atherosclerosis by modulating the microbiota-dependent TMA-TMAO metabolic axis","authors":"Shurui Zhang ,&nbsp;Han Feng ,&nbsp;Jingting Jiang ,&nbsp;Sunye Feng ,&nbsp;Yujie Jiang ,&nbsp;Guangjian Chen ,&nbsp;Yunjie Wu ,&nbsp;Ronghui Liu ,&nbsp;Yuxin Ma ,&nbsp;Yuting Ma ,&nbsp;Yu Li ,&nbsp;Huimin Bian ,&nbsp;Qinghai Meng ,&nbsp;Ruigong Zhu","doi":"10.1016/j.phymed.2025.157318","DOIUrl":"10.1016/j.phymed.2025.157318","url":null,"abstract":"<div><h3>Background</h3><div>Trimethylamine N-oxide (TMAO), a product of the gut microbiota, is essential to the pathophysiology of atherosclerotic cardiovascular disease (ASCVD). Although Liuwei Dihuang Formula (LWDH) can ameliorate perimenopausal atherosclerosis (AS) and modulate gut microbes, it is unknown how it regulates the trimethylamine (TMA)-TMAO pathway.</div></div><div><h3>Purpose</h3><div>This study aimed to examine whether LWDH could attenuates perimenopausal AS by modulating the gut microbiota-TMA-TMAO axis and to clarify the associated mechanisms, with an emphasis on its possible synergistic interaction with the probiotic <em>Bifidobacterium animalis subsp. Lactis</em> (<em>B.</em> <em>lactis</em>).</div></div><div><h3>Methods</h3><div>In ApoE knockout (ApoE^-/-) mice, a perimenopausal AS model was established <em>via</em> bilateral ovariectomy combined with a high-fat diet (HFD), followed by LWDH intervention. The TMAO and TMA levels in plasma and the liver were measured using targeted metabolomics. Microbial communities were analyzed using 16S rRNA sequencing. <em>In vitro</em> microbial culture experiments were carried out to validate the LWDH effect on the key bacterial populations and metabolic pathways. A combined intervention with LWDH and <em>B.</em> <em>lactis</em> was also performed to evaluate the potential synergistic effects.</div></div><div><h3>Results</h3><div>LWDH significantly reduced aortic plaque burden and decreased plasma and hepatic TMAO levels in perimenopausal AS mice. Mechanistic analyses revealed that LWDH remodeled the gut microbiota, suppressed TMA-producing bacteria, and enhanced TMA degradation, thereby reducing systemic TMAO accumulation. Notably, 16S rRNA sequencing revealed a close link between decreased <em>Bifidobacterium</em> abundance and elevated TMAO levels. <em>In vitro</em> assays confirmed that LWDH enhanced the TMA-degrading activity of <em>B. lactis</em> and downregulated the <em>cutC</em> gene in <em>Escherichia coli</em>, resulting in reduced TMA synthesis. Combined LWDH and <em>B.</em> <em>lactis</em> intervention led to greater reductions in plasma TMAO compared to <em>B. lactis</em> alone, accompanied by improved lipid metabolism and attenuation of systemic inflammation.</div></div><div><h3>Conclusion</h3><div>These findings are the first to show that LWDH mitigated perimenopausal AS progression by modulating the gut microbiota-dependent TMA-TMAO axis. The dual mechanisms of enhancing TMA degradation and inhibiting TMA production, together with the synergistic effects of LWDH and <em>B. lactis</em>, highlight a novel therapeutic strategy that integrates traditional Chinese medicine and probiotics for AS management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157318"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192486","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":"Anticancer effects and mechanisms of genus Dioscorea: A review","authors":"Li Liu ,&nbsp;Yiwen Bao ,&nbsp;Yanfang Chen ,&nbsp;Meiling Ding ,&nbsp;Huan Liang ,&nbsp;Bin Li ,&nbsp;Xinyu Qin ,&nbsp;Nan Zeng","doi":"10.1016/j.phymed.2025.157328","DOIUrl":"10.1016/j.phymed.2025.157328","url":null,"abstract":"<div><h3>Background</h3><div><em>Dioscorea</em>, as a plant genus, possesses dual value for both medicinal and dietary purposes. Recently, numerous studies have demonstrated that the genus <em>Dioscorea</em> extracts (DEs) and their compounds (DCs) exhibit significant anticancer properties.</div></div><div><h3>Purpose</h3><div>This review summarizes pharmacological mechanisms, toxicology, and clinical studies of <em>Dioscorea</em> to evaluate its potential for novel anticancer drug development.</div></div><div><h3>Methods</h3><div>A systematic search was performed across PubMed, Web of Science, and CNKI databases. The search was conducted from the time of database construction to August 2024. A total of 1742 articles were searched, and after screening, 83 articles were finally included in this study.</div></div><div><h3>Results</h3><div>The analysis of 83 articles revealed that DEs and DCs exert their anticancer effects through six primary mechanisms: (1) promotion of apoptosis, (2) prevention of cancer cell proliferation, (3) suppression of tumor metastasis, (4) activation of autophagy, (5) modulation of immune responses, and (6) prevention of cancer development.</div></div><div><h3>Conclusion</h3><div>DCs and DEs exhibit broad-spectrum anticancer properties. In particular, dioscin exhibits low toxicity and exerts strong anticancer effects through multiple pathways and targets. Future studies should focus on investigating these DEs and DCs, especially dioscin, as a novel anticancer agent.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157328"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207214","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":"Angelica sinensis and Scutellaria baicalensis synergistically alleviates metabolic dysfunction-associated steatohepatitis via promoting adipose tissue-to-liver tissue communication","authors":"Meina Zhao ,&nbsp;Xingru Tao ,&nbsp;Kai Gao ,&nbsp;Dong Xu ,&nbsp;Wei Zhang ,&nbsp;Fei Mu ,&nbsp;Rui Lin ,&nbsp;Mengdan Hui ,&nbsp;Jingwen Wang","doi":"10.1016/j.phymed.2025.157329","DOIUrl":"10.1016/j.phymed.2025.157329","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The synergistic use of Danggui (&lt;em&gt;Angelica sinensis&lt;/em&gt;, As) and Huangqin (&lt;em&gt;Scutellaria baicalensis&lt;/em&gt; or &lt;em&gt;Scutellaria baicalensis Georgi&lt;/em&gt;, SbG; As-SbG) exhibits a notable therapeutic effect on metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying pharmacological mechanisms of their synergistic action have not yet been fully elucidated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aims to evaluate the therapeutic efficacy of the synergistic application of As-SbG on MASH induced by various dietary patterns, and to identify the specific potential active compounds, underlying pharmacological mechanisms, and key therapeutic targets responsible for its anti-MASH effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Two MASH animal models induced by methionine- and choline- deficient (MCD) diet and high-fat/high-cholesterol (HFHC) diet were constructed to compare the efficacy of As, SbG and As-SbG synergistic treatment on adipose tissue and liver tissue during MASH progression. Potential mechanistic pathways and key molecular targets were identified through proteomics analysis. The chemical components of As-SbG were characterized using ultrahigh performance liquid chromatography-high resolution mass spectrometry (UPLC-&lt;img&gt;HRMS). The interactions between the identified bioactive components and the key targets from proteomics were further validated using molecular docking methods, focusing on As-SbG’s therapeutic potential. Based on these bioinformatics findings, qRT-PCR, immunofluorescence staining, and Western blotting were employed to elucidate the regulatory mechanisms of As-SbG combination therapy on lipid metabolism, inflammation, and apoptosis-related pathways in both in vitro and in vivo MASH models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Compared with single-flavor administration of As and SbG, As-SbG synergistic administration significantly restored the balance among different phenotypes, functions, and sizes of various adipose tissues in MASH-induced mice under different dietary conditions, ameliorated hepatic steatosis and liver damage. Proteomic analysis revealed that the potential synergistic therapeutic effects of As-SbG on MASH were primarily associated with pathways involved in fat metabolism, anti-inflammatory responses, and anti-apoptotic mechanisms. Mechanism exploration revealed that the As-SbG synergistic therapy enhanced the expression of Nrg4 in adipose tissue, which specifically bound to ErbB receptors in liver tissue. This interaction activated the downstream PI3K/Akt, Ras/MAPK, and P53 signaling pathways, thereby promoting inter-tissue communication between adipose and liver tissues. Consequently, this regulatory effect improved hepatic lipid metabolism, suppressed inflammatory responses, and reduced hepatocellular damage, fibrosis, and apoptosis, ultimately ameliorating MASH. Furthermore, pharmacological inhibition of the key target ErbB4 in vitro abolished the p","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157329"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213328","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":"Alpha-linolenic acid reverses colorectal cancer drug resistance by suppressing secreted phosphoprotein 1 expression and tumor stemness","authors":"Songtao Li ,&nbsp;Tianxing Lv ,&nbsp;Xiaxia Fan ,&nbsp;Mangmang Feng ,&nbsp;Meng Zhou ,&nbsp;Zhuoyu Li","doi":"10.1016/j.phymed.2025.157310","DOIUrl":"10.1016/j.phymed.2025.157310","url":null,"abstract":"<div><h3>Background</h3><div>Chemotherapy remains the main treatment for colon cancer, but the development of resistance has limited its efficacy. There is an urgent need to exploit a more effective therapeutic strategy. Alpha-linolenic acid (ALA), as an essential nutrient for the human body, has been found to increase the therapeutic effect of chemotherapy drugs.</div></div><div><h3>Purpose</h3><div>Exploring the potential mechanism of alpha linolenic acid reversing chemotherapy resistance in colon cancer.</div></div><div><h3>Results</h3><div>ALA reverses chemoresistance in colorectal cancer and suppresses stemness in resistant colorectal cancer cells. SPP1 functions as a key mediator in ALA-induced reversal of chemoresistance; its downregulation disrupts the interaction with the downstream receptor CD44, thereby mitigating chemotherapy resistance. Subsequently, ALA inhibits the expression of SOX2, a transcription factor that promotes SPP1 transcription. Further analysis reveals that decreased SPP1 expression leads to reduced levels of FAP, a marker of cancer-associated fibroblasts (CAFs), and that a functional interaction exists between SPP1 and FAP. Interestingly, ALA disrupts the interaction between SPP1 and FAP, thereby preventing CAFs accumulation. In vivo studies confirm that ALA reverses colorectal cancer chemoresistance via the SOX2/SPP1/FAP signaling axis.</div></div><div><h3>Conclusion</h3><div>The study demonstrates that ALA in quinoa depresses the stemness of colorectal cancer and reduces the number of CAFs via SPP1, thereby reversing chemotherapy resistance. These findings highlight ALA as a promising dietary-based adjuvant for enhancing chemotherapy efficacy in colorectal cancer and provide new mechanistic insights into targeting tumor stemness and stromal remodeling.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157310"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225920","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":"Exploring the immunomodulatory mechanisms of Shiyiwei Shenqi tablets in NSCLC: N-acetylaspartate as a biomarker for modulating M1/M2 macrophage balance.","authors":"Mingming Wang, Xuewen Yang, Qian Zhang, Yue Qiu, Jiameng Qu, Huarong Xu, Qing Li","doi":"10.1016/j.phymed.2025.157325","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157325","url":null,"abstract":"<p><strong>Background: </strong>Macrophages, with their dual role in immune regulation and metabolic characteristics, are emerging as the pivotal target in tumor treatments. Shiyiwei Shenqi tablets (SST) is widely used for its immunomodulatory effects in non-small cell lung cancer (NSCLC). However, its mechanism remains unclear.</p><p><strong>Purpose: </strong>This study sought to investigate whether SST regulates immunity in NSCLC through macrophages and to elucidate its underlying mechanisms.</p><p><strong>Methods: </strong>The immunomodulatory mechanisms were initially predicted using the random walk with restart (RWR) algorithm and subsequently verified using the Lewis lung carcinoma model and macrophage cell depletion experiment. The regulatory effects of SST on macrophage phenotype and function were testified through flow cytometry, Western blot, qRT-PCR, ELISA, wound healing, migration, and tube formation assays. Furthermore, non-targeted and targeted metabolomics, combined with molecular studies, were employed to investigate the immunometabolic mechanisms in macrophages.</p><p><strong>Results: </strong>SST treatment markedly impeded tumor progression and identified macrophages as the target cells for enhancing CD8⁺ T cell immunity against tumors. Specifically, SST reprogrammed macrophages by polarizing towards an M1-like phenotype while inhibiting the M2-like phenotype, reducing M2-driven angiogenesis and metastasis. Mechanistically, SST inhibited glutamine (Gln) metabolism, with N-acetylaspartate (NAA), a downstream metabolite of Gln, identified as a key regulator across macrophage phenotypes. SST suppressed NAA by downregulating NAT8L and upregulating ASPA, thereby relieving NAA-mediated suppression of NF-κB activation.</p><p><strong>Conclusion: </strong>SST enhanced anti-tumor immunity in NSCLC by promoting M1 macrophages and suppressing M2 macrophages. NAA, a macrophage-derived biomarker, highlighted SST's role in regulating M1/M2 balance.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157325"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245043","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":"Astragaloside IV potentiates cisplatin sensitivity in triple-negative breast cancer via STING signaling pathway activation","authors":"Bufan Bai ,&nbsp;Luyao Zhang ,&nbsp;Yifei Zhang ,&nbsp;Rushuang Yue ,&nbsp;Yiyu Lu ,&nbsp;Rong Shi ,&nbsp;Qianmei Zhou","doi":"10.1016/j.phymed.2025.157330","DOIUrl":"10.1016/j.phymed.2025.157330","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Astragaloside IV (As), a bioactive tetracyclic triterpenoid saponin from Astragalus membranaceus, exhibits diverse pharmacological properties including anti-inflammatory, anticancer and immunomodulatory activities. However, its potential role as a targeted therapeutic agent for cisplatin sensitization in triple-negative breast cancer (TNBC) via the STING signaling pathway remains unexplored.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to investigate the cisplatin-sensitizing potential of As in TNBC and elucidate its underlying molecular mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Bioinformatic analysis identified key module genes from public databases using weighted gene co-expression network analysis (WGCNA), followed by feature selection via least absolute shrinkage and selection operator (LASSO) regression. Immune microenvironment characterization was performed using CIBERSORT deconvolution analysis. Potential targets of As in TNBC were systematically identified through multi-database mining, protein-protein interaction (PPI) network construction, pathway enrichment analysis and molecular docking simulations. Transcriptomic profiling revealed treatment-induced differentially expressed genes and enriched signaling pathways in murine tissues. The combinatorial anti-tumor efficacy was evaluated using orthotopic TNBC model (4T1 cell-derived) &lt;em&gt;in vivo&lt;/em&gt; and 4T1, MDA-MB-231, and MCF-7 cell lines &lt;em&gt;in vitro&lt;/em&gt;. Mechanistic validation was conducted through integrated &lt;em&gt;in vivo&lt;/em&gt; and &lt;em&gt;in vitro&lt;/em&gt; experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Integrated bioinformatics analysis (WGCNA, LASSO, and CIBERSORT) identified STING within a chemotherapy-sensitive module among six endoplasmic reticulum (ER)-associated gene co-expression networks. STING exhibited significant enrichment in antitumor immune pathways and correlated with heterogeneous immune cell infiltration. KEGG pathway analysis implicated immune/inflammatory signaling and DNA damage responses in the cisplatin-sensitizing effects of As. Molecular docking confirmed stable binding between As and STING (binding energy: -36.09 kcal/mol). &lt;em&gt;In vivo&lt;/em&gt;, As synergistically enhanced cisplatin’s tumor growth inhibition while mitigating cisplatin-induced toxicity, including weight loss, nephrotoxicity, and systemic inflammation. Transcriptomic and immunohistochemical analyses validated As-mediated DNA damage, STING pathway activation, immune cell recruitment. &lt;em&gt;In vitro&lt;/em&gt; mechanistic studies using DNase I and STING inhibitor (C-176) demonstrated As potentiated cisplatin via cell cycle arrest, mitochondrial dysfunction and STING cascade activation. C‐176 weakened the antitumor activity of As- cisplatin combination treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;As synergistically enhances the therapeutic efficacy of cisplatin against TNBC while ameliorating its adverse effects, primarily through activation of the STING signaling p","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157330"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186024","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":"Anti-tumor effects of Cinnamomum camphora essential oil in breast cancer via NOX4 modulation by (+)-2-bornanone","authors":"Ruzhen Zheng ,&nbsp;Yibo He ,&nbsp;Yi Wang ,&nbsp;Yidan Chen ,&nbsp;Lingrong Yang ,&nbsp;Rui Wang ,&nbsp;Shiyan Wu ,&nbsp;Hualing Xie ,&nbsp;Shangnao Xie","doi":"10.1016/j.phymed.2025.157327","DOIUrl":"10.1016/j.phymed.2025.157327","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is the most prevalent malignancy among women. <em>Cinnamomum camphora</em> essential oil (CCEO) has shown potential in cancer therapy, but its anti-tumor components and mechanisms in BC remain unclear. NADPH oxidase 4 (NOX4) is an important producer of reactive oxygen species (ROS), driving cancer progression and serving as a potential therapeutic target.</div></div><div><h3>Purpose</h3><div>To investigate the anti-tumor activity of CCEO, characterize its active compounds, and clarify its molecular mechanisms.</div></div><div><h3>Methods</h3><div>The anti-tumor effects of CCEO were assessed in BC cell lines via MTT assays, western blot, and flow cytometry. The modulation of signaling pathways was analyzed via western blot and RT-qPCR. Xenograft tumor models were employed to evaluate efficacy and safety <em>in vivo</em>. Gas chromatography-mass spectrometry (GC–MS) was used to identify major constituents of CCEO, and NOX4 overexpression assays were conducted to explore molecular mechanisms.</div></div><div><h3>Results</h3><div>CCEO exhibited significant anti-tumor activity both <em>in vitro</em> and <em>in vivo</em> by inducing apoptosis and senescence, decreasing intracellular ROS levels, inhibiting migration and invasion, and causing cell cycle arrest. GC–MS analysis identified (+)-2-Bornanone as the predominant active component responsible for anti-tumor effects. Mechanistically, (+)-2-Bornanone suppressed NOX4 expression, which inhibited the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, ultimately suppressing tumor progression.</div></div><div><h3>Conclusion</h3><div>The anti-tumor effects of CCEO in triple-negative breast cancer (TNBC) are principally mediated by (+)-2-Bornanone, which inhibits the MAPK/ERK pathway via NOX4 downregulation. These findings reveal a novel anti-tumor mechanism and provide a strong rationale for further developing (+)-2-Bornanone as a promising natural therapeutic agent for BC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157327"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159350","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":"Astragaloside IV reduces hepatitis B surface antigen level via monocyte/macrophages in chronic HBV infection mice.","authors":"Mengling Jiang, Meifang Tang, Lifen Zhu, Pei Zhou, Haiyi Cai, Qinghong Fan, Xiaoqian Wang, Yaping Wang, Jianming Liang, Feng Li, Xinghua Tan","doi":"10.1016/j.phymed.2025.157308","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157308","url":null,"abstract":"<p><strong>Background: </strong>Astragaloside IV (AS-IV) is one main bioactive component in the herb Astragalus membranaceus that is commonly used to enhance human immune function. However, its extremely low aqueous solubility severely restricts its absorption in the body, thereby limiting its potential for clinical translation. Despite its established immunomodulatory and antiviral properties against several viruses, the therapeutic effect of AS-IV on chronic Hepatitis B Virus (HBV) infection-especially its ability to reduce hepatitis B surface antigen (HBsAg), a key target for functional cure of HBV-remains insufficiently investigated.</p><p><strong>Purpose: </strong>This study aimed to address the poor bioavailability of AS-IV by developing a novel nanoformulation, and investigate its therapeutic efficacy and underlying mechanisms in a chronic recombinant adeno-associated virus (AAV) carrying a replicable HBV genome (AAV-HBV) mouse model.</p><p><strong>Study design: </strong>AS-IV nanoparticles were prepared using different packaging strategies. Their therapeutic benefit was evaluated on AAV-HBV mouse model by measuring hepatitis B surface antigen (HBsAg) levels.</p><p><strong>Methods: </strong>The nanoparticles were quality controlled by Malvern Laser Particle Size Analyzer, Transmission Electron Microscopy, and Infrared Spectroscopy. Immune mechanisms were dissected by single-cell RNA sequencing (scRNA-seq) and flow cytometry.</p><p><strong>Results: </strong>Among all tested formulations, Pluronic® F-127-formulated AS-IV (P-AS) exhibited the best performance, with significantly improved aqueous solubility, uniform spherical morphology (100-150 nm), and good in vivo safety (no obvious hepatotoxicity or systemic toxicity). P-AS treatment reduced serum HBsAg levels (approximately 50 %, p < 0.0001) without altering HBV RNA expression, suggesting that the reduction of HBsAg is mediated through a post-transcriptional mechanism. scRNA-seq analysis revealed that P-AS markedly increased hepatic infiltration of myeloid cells, especially monocyte/macrophages (over 2-fold). Furthermore, P-AS induced the polarization of these cells toward the classically activated macrophage (M1) phenotype, enhanced their phagocytosis, and activated key pro-inflammatory pathways. Critically, depletion of monocyte/macrophages completely abrogated the HBsAg-lowering effect of P-AS, confirming that the therapeutic efficacy of P-AS depends on the recruitment and functional activation of monocyte/macrophages.</p><p><strong>Conclusion: </strong>This study successfully developed a Pluronic® F-127-based AS-IV nanoformulation (P-AS) with enhanced bioavailability and safety. P-AS effectively reduces serum HBsAg levels in chronic HBV-infected mice through a monocyte/macrophage-dependent mechanism, providing a promising preclinical basis for the development of AS-IV-based nanotherapeutics for chronic hepatitis B treatment.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157308"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233194","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":"Genkwanin reduces airway epithelial cell ferroptosis and alleviates asthma symptoms in mice","authors":"Xun Chen ,&nbsp;Jing Liu ,&nbsp;Zimeng An ,&nbsp;Min Li ,&nbsp;Xiaohua Ji ,&nbsp;Jing Huang ,&nbsp;Xiaoru Yan","doi":"10.1016/j.phymed.2025.157306","DOIUrl":"10.1016/j.phymed.2025.157306","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the role of genkwanin (GKA) in pediatric asthma.</div></div><div><h3>Methods</h3><div>Newborn mice were exposed to house dust mites and treated with GKA to examine airway epithelial cell damage and airway remodeling. The targets of GKA were predicted and verified.</div></div><div><h3>Results</h3><div>After medium-dose GKA (M-GKA) treatment, HDM-IgE, HDM-IgG1, IL-5, IL-13, and IL-4 decreased by 28 %, 22 %, 32 %, 48 %, and 38 %, respectively. M-GKA reduced collagen formation by 28 % and MUC5AC protein expression by 30 % in mice. M-GKA reduced Fe2+ content by 32 % and ROS levels by 21 % in airway epithelial cells by inhibiting DYRK1A activity. DYRK1A increased TFE3 cytoplasmic retention by 73 % through enhancing its serine phosphorylation (by 133 %), leading to suppression of LC3BII/I and ATG5 by 32 % and 37 %, and promotion of MDA content by 263 % and ROS accumulation by 43 %. TFE3 triggered autophagy to mitigate ferroptosis (Fe2+ and ROS contents were decreased by 59 % and 25 %, while GPX4 and SLC7A11 were downregulated by 104 % and 88 %). TFE3 knockout weakened the alleviation of airway epithelial cell ferroptosis by GKA, as evidenced by increased Fe2+ content (89 %), MDA and ROS accumulation (73 % and 44 %, respectively). Additionally, it blocked autophagy, as indicated by decreased LC3B (58 %) and ATG5 (51 %) expression.</div></div><div><h3>Conclusions</h3><div>GKA inhibits TFE3 phosphorylation via DYRK1A, thereby driving TFE3 nuclear translocation and activating autophagy, which suppresses ferroptosis in airway epithelial cells. This study identifies GKA as a therapeutic candidate for asthma, and screening of additional flavones will be valuable to map the structural features that confer this activity.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157306"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226878","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}