Phytomedicine最新文献

{"title":"10-Hydroxydec-2-enoic acid reduces vascular smooth muscle cell inflammation via interacting with Toll-like receptor 4","authors":"Feng Jia ,&nbsp;Yongqing Wang ,&nbsp;Zhiqiang Chen ,&nbsp;Jingxian Jin ,&nbsp;Lei Zeng ,&nbsp;Li Zhang ,&nbsp;Huaijian Tang ,&nbsp;Yanyan Wang ,&nbsp;Pei Fan","doi":"10.1016/j.phymed.2025.156534","DOIUrl":"10.1016/j.phymed.2025.156534","url":null,"abstract":"<div><h3>Background</h3><div>10-Hydroxydec-2-enoic acid (10-HDA), a unique and marker compound in royal jelly, has a wide range of bio-activities. However, its role in regulating inflammation of vascular smooth muscle cell (VSMC), which is essential to a set of vascular diseases, is still unknown.</div></div><div><h3>Purpose</h3><div>Our study aimed to investigate whether 10-HDA exerts effect on VSMC inflammation via interacting with toll-like receptor 4 (TLR4), a pivotal inflammatory initiator.</div></div><div><h3>Methods</h3><div>A package of proteins, which might participate in TLR4-mediated signaling, influenced by 10-HDA were analyzed in mouse VSMCs with Angiotensin Ⅱ(Ang Ⅱ) or lipopolysaccharide (LPS) stimulation. Accordingly, pro- or anti-inflammatory cytokines, reactive oxygen species (ROS), and anti-oxidants that are closely relevant to inflammatory process were determined. The possible mode for 10-HDA interacting with TLR4 was also characterized. Moreover, involvement of a key miRNA in 10-HDA regulating VSMC inflammation was identified.</div></div><div><h3>Results</h3><div>In the presence of Ang Ⅱ, 10-HDA inhibited the TLR4 expression in a dose-dependent manner. In such occasion, 10-HDA hindered the up-regulation of specificity protein 1 (SP1) and serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C), the phosphorylation of extracellular signal-regulated kinase 1/2, TGF-β-activated kinase 1, and nuclear factor-κB p56, as well as the enhancement of myeloid differentiation primary response gene 88. Apart from SP1 and PPP6C, the level change of these proteins by 10-HDA was similar with LPS stimulation. The effect might be resulted from 10-HDA blocking TLR4 through multiple atomic interactions. 10-HDA mitigated the increase of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-2 (IL-2), and IL-6, as well as increased the anti-inflammatory cytokine IL-10, in the Ang Ⅱ- or LPS-induced VSMCs. Correspondingly, the level of ROS was attenuated and the anti-oxidants such as glutathione and superoxide dismutase were fortified. The data indicated the anti-inflammatory potential of 10-HDA in VSMCs, which was associated with 10-HDA's capability of relieving oxidative stress. Additionally, the expression of miR-17–5p was saved by 10-HDA from Ang Ⅱ- or LPS-treated VSMCs, which might be relevant to SP1 and PPP6C targeting.</div></div><div><h3>Conclusion</h3><div>The present work of 10-HDA, for the first time, revealed its ability to alleviate VSMC inflammation by targeting TLR4 and therefore modulate the downstream inflammatory participants. Our data will cast light on the utilization of 10-HDA in VSMC inflammation-related vascular disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156534"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiqi Baizhu decoction enhances radiosensitivity in non-small cell lung cancer by inhibiting the HIF-1α/DNA-PKcs axis-mediated DNA repair","authors":"Yangyang Li ,&nbsp;Gengqiang Yang ,&nbsp;Qiyang Li ,&nbsp;Yiming Zhang ,&nbsp;Shangzu Zhang ,&nbsp;Ting Zhou ,&nbsp;Xin Wang ,&nbsp;Fuxian Liu ,&nbsp;Zhiming Miao ,&nbsp;Yafeng Qi ,&nbsp;Liying Zhang ,&nbsp;Yongqi Liu ,&nbsp;Haixiang Su","doi":"10.1016/j.phymed.2025.156591","DOIUrl":"10.1016/j.phymed.2025.156591","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Radiotherapy is one of the main treatments for non-small cell lung cancer (NSCLC), and radiosensitivity is a determinant of its efficacy. Therefore, enhancing the radiosensitivity is of great significance to improve the clinical efficacy of non-small cell lung cancer (NSCLC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study intended to investigate the radiosensitisation effect and mechanism of Guiqi Baizhu decoction (GQBZD) on non-small cell lung cancer (NSCLC) and the role of hypoxia-inducible factor-1 alpha (HIF-1α)/DNA-dependent protein kinase catalytic subunit (DNA-PKcs) axis-mediated DNA non-homologous end joining (NHEJ) repair in NSCLC radiotherapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice, and &lt;em&gt;in vitro&lt;/em&gt; experimental models were A549, H1299 and H460 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice. After the model was successfully established, the tumor was irradiated locally with 4 Gy X-ray, and 10.465 g/kg Guiqi Baizhu Decoction (GQBZD) was administered by gavage on the second day after irradiation for a total of 10 days. The morphological changes in tumour tissues were observed by HE staining, Ki67 levels in tumour tissues were detected by immunohistochemistry, the apoptosis in tumour cells were detected by Tunel staining. &lt;em&gt;In vitro&lt;/em&gt; experimental models were different NSCLC cells (A549, H1299 and H460), irradiated by 2 Gy X-rays and then intervened with 5%, 10% and 20% Guiqi Baizhu Decoction (GQBZD)-containing serum for 24 h. A549 stably-transformed cell lines knocking down and overexpressing HIF-1α were also constructed by lentiviral transfection. The cell proliferation was detected by CCK-8 and clone formation, the apoptosis and cell cycle was detected by flow cytometry. Network pharmacology and transcriptomics to investigate key targets and pathways of GQBZD effects on NSCLC irradiation, further validated by immunofluorescence and Western blot.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experiments confirmed that GQBZD combined with irradiation could inhibit the growth of Lewis subcutaneous transplantation tumor, reduce the expression of Ki67 and promote the apoptosis of tumour cells. &lt;em&gt;In vitro&lt;/em&gt; experiments confirmed that GQBZD combined with irradiation inhibited the proliferation of different NSCLC cells, promoted NSCLC cell apoptosis and G2/M-phase arrest, and induced the expression of phosphorylated histone H2AX (γ-H2AX) in NSCLC cells, which showed a good radiosensitisation effect. Mechanistically, GQBZD exerts its radiosensitisation effect on NSCLC mainly through the HIF-1α signalling pathway. Meanwhile, under irradiation conditions, the expression of HIF-1α and DNA-PKcs were positively correlated, and HIF-1α had a regulatory effect on DN","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156591"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deoxyshikonin from Arnebiae Radix promotes hair growth by targeting the Wnt/β-catenin signaling pathway","authors":"Yingna Li ,&nbsp;Yanhong Mu ,&nbsp;Xinyue Chen ,&nbsp;Yiming Zhao ,&nbsp;Chunlei Ji ,&nbsp;Rong Xu ,&nbsp;Rui Jiang ,&nbsp;Fangbing Liu ,&nbsp;Manying Wang ,&nbsp;Liwei Sun","doi":"10.1016/j.phymed.2025.156590","DOIUrl":"10.1016/j.phymed.2025.156590","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia is a common skin condition with limited effective treatments. <em>Arnebiae Radix</em> (AR) is a traditional Asian herb used for various skin disorders. However, its specific components and the mechanisms underlying its hair growth-promoting effects remain elusive. Therefore, this study aimed to investigate the primary active components in AR that are responsible for hair growth as well as determine the molecular mechanisms responsible for treating alopecia.</div></div><div><h3>Methods</h3><div>Alopecia areata mice were employed to assess the influence of AR extracts on hair growth. The active AR components were identified <em>via</em> High-Performance Liquid Chromatography (HPLC). Furthermore, network pharmacology and molecular docking were carried out to predict the key targets of the main active AR compound, which were validated by Surface Plasma Resonance (SPR) analysis. Moreover, the mechanism of action of the identified active AR compound on human dermal papilla cells (HDPCs) and alopecia areata mice was investigated to determine its effects on relevant signaling pathways.</div></div><div><h3>Results</h3><div>It was found that Deoxyshikonin (Ds) was the active component in AR with hair growth-promoting potential. Furthermore, it was predicted that Ds targeted 112 alopecia-related targets, including biological processes (such as positive modulation of cell migration and protein phosphorylation) and pathways (including cell cycle- and Wnt signaling pathway-related genes pathways). Network analysis revealed that CCND1 and GSK3β were the hub targets of Ds when treating alopecia. Molecular docking showed a strong binding affinity between Ds and GSK3β, which was validated by SPR results. Moreover, Ds improved HDPC's proliferation ability and promoted hair regeneration in alopecia mice. Similarly, Ds increased VEGF and IGF-1, reduced TGF-β1 content and GSK3β expression, and enhanced the p-GSK3β and β-catenin expression in the Wnt/β-catenin pathway.</div></div><div><h3>Conclusion</h3><div>This study showed that Ds was the main active AR component with promising potential as a hair growth stimulant. Mechanistically, Ds primarily targets GSK3β to promote the Wnt/β-catenin signaling pathway. This suggests that Ds could be an innovative therapeutic candidate for promoting hair regeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156590"},"PeriodicalIF":6.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549431","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":"Alkannin triggered apoptosis and ferroptosis in gastric cancer by suppressing lipid metabolism mediated by the c-Fos/SREBF1 axis","authors":"Huayang Yu ,&nbsp;Qiming Kou ,&nbsp;Hang Yuan ,&nbsp;Yanyu Qi ,&nbsp;Qin Li ,&nbsp;Liang Li ,&nbsp;Gang Zhao ,&nbsp;Guanru Wang ,&nbsp;Siqi Li ,&nbsp;Jie Qu ,&nbsp;Hongbai Chen ,&nbsp;Minghui Zhao ,&nbsp;Qijing Wang ,&nbsp;Shan Li ,&nbsp;Kang Chen ,&nbsp;Chenghong Lu ,&nbsp;Hengyi Xiao ,&nbsp;Ping Lin ,&nbsp;Kai Li","doi":"10.1016/j.phymed.2025.156604","DOIUrl":"10.1016/j.phymed.2025.156604","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC), one of the most common malignancies with high mortality worldwide, currently requires beneficial therapeutic strategies. Alkannin is the primary active component of <em>Lithospermum erythrorhizon</em> and has been shown to have potential anticancer effects on a variety of cancers. However, the specific effects and molecular mechanisms of alkannin against GC remain unknown.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the detailed role and downstream effectors of alkannin in the treatment of GC.</div></div><div><h3>Methods</h3><div>The functions of alkannin on the proliferation, migration and invasion of GC cells were measured via CCK-8, EdU, colony formation, LDH release, flow cytometry, wound healing, and Transwell assays. BODIPY-C11 staining, determination of cellular ferrous iron, MDA and GSH levels, and western blotting were used to evaluate alkannin-induced ferroptosis. Transcriptome sequencing was analyzed to identify differentially expressed genes. Nile red staining and cholesterol and triglyceride assays were utilized to examine changes in lipid metabolism. Transcriptional regulation was determined by real-time PCR, dual-luciferase reporter and chromatin immunoprecipitation assays. Finally, a xenograft animal model was employed to assess tumor growth <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Alkannin inhibited growth and motility and simultaneously triggered apoptotic and ferroptotic cell death in GC cells. Transcriptome sequencing analysis revealed that alkannin treatment downregulated c-Fos expression. The overexpression of c-Fos conferred the GC cells to tolerate alkannin <em>in vitro</em> and <em>in vivo</em>. Moreover, we confirmed that c-Fos activated SREBF1 transcription by directly binding to TPA-responsive elements within the SREBF1 promoter, leading to increased expression of lipid biosynthesis-related genes, which counteracted ferroptosis through the maintenance of cellular lipid homeostasis.</div></div><div><h3>Conclusion</h3><div>Our present study provides the first evidence that alkannin induces both apoptosis and ferroptosis in GC cells and reveals a novel mechanism by which alkannin restrains c-Fos-dependent SREBF1 transcriptional activation, leading to lipid metabolism and redox homeostasis disorders. Our findings highlight that alkannin is an available and promising natural product for the avoidance of drug resistance and the clinical treatment of GC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156604"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550271","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 GATA6 with pedunculoside inhibits fetal gene expression to attenuate pathological cardiac hypertrophy","authors":"An Pan ,&nbsp;Anqi Shi ,&nbsp;Huanhuan Chen,&nbsp;Lina Jiang,&nbsp;Qiang Zhang,&nbsp;Jiayi Feng,&nbsp;Jinting He,&nbsp;Jian Liu,&nbsp;Junwei Wang,&nbsp;Lihong Hu","doi":"10.1016/j.phymed.2025.156603","DOIUrl":"10.1016/j.phymed.2025.156603","url":null,"abstract":"<div><h3>Background</h3><div>Pathological cardiac hypertrophy is a characteristic feature of numerous cardiovascular diseases and significantly impacts human health. However, effective treatment options for cardiac hypertrophy are still significantly unmet. Pedunculoside, a pentacyclic triterpenoid saponin from the traditional Chinese herb <em>Ilex rotunda</em> Thunb., exhibits various pharmacological properties such as anti-inflammatory and cardiovascular therapeutic effects, but its anti-hypertrophy efficacy and mechanisms have not yet been reported.</div></div><div><h3>Purpose</h3><div>This study aimed to confirm the ameliorating effect of pedunculoside on cardiac hypertrophy and elucidate its underlying mechanism.</div></div><div><h3>Methods</h3><div>To investigate the effect of pedunculoside on cardiac hypertrophy, we used transverse aortic constriction (TAC) and isoproterenol hydrochloride (ISO) infusion to induce cardiac hypertrophy model in mice. Angiotensin II (Ang II) was used to mimic hypertrophy model in myocardial cells. Then, we utilized a biotin-tagged carabrone chemical probe and validation experiments to pinpoint pedunculoside's key targets. Further, molecular docking study and sites mutation were used to predict and identify the binding modes of pedunculoside to target. Finally, structural optimization was carried out to find new pedunculoside derivatives with stronger anti-hypertrophy activity and binding affinity to the target.</div></div><div><h3>Results</h3><div>Our findings revealed for the first time that pedunculoside treatment significantly attenuated hypertrophic phenotypes in response to TAC and ISO. It also effectively reduced hypertrophy and fibrosis in myocardial cells exposed to Ang II stimulation. Mechanically, we identified transcription factor GATA-6 (GATA6) as a key target of pedunculoside for treating cardiac hypertrophy. Further studies demonstrated that pedunculoside blocks cardiac hypertrophy progression by inhibiting the transcriptional activation of GATA6 on promoting fetal gene expression. More importantly, a new pedunculoside derivative <strong>PE-3</strong> with stronger anti-hypertrophy activity and affinity for GATA6 was discovered.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that pedunculoside and <strong>PE-3</strong> could be developed as promising drug candidates for cardiac hypertrophy treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156603"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549535","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":"Modulation of Pseudomonas aeruginosa-induced avoidance behavior by Shen Qi pills via mitogen-activated protein kinase PMK-1 and forkhead box protein O DAF-16 in Caenorhabditis elegans","authors":"Hanxiao Wang ,&nbsp;Siyi Lin ,&nbsp;Yingying Xu ,&nbsp;Huangjie Fu ,&nbsp;Meiqi Shen ,&nbsp;Ping Qiu ,&nbsp;Changyu Li ,&nbsp;Thomas Efferth ,&nbsp;Chunlan Hong","doi":"10.1016/j.phymed.2025.156585","DOIUrl":"10.1016/j.phymed.2025.156585","url":null,"abstract":"<div><h3>Background</h3><div>Avoidance behavior is one of the core features of anxiety and related in-depth study can help to reveal the biological basis of these disorders. In recent years, traditional Chinese medicine has incorporated <em>Shen Qi</em> pills to treat neuropsychiatric disorders, such as depression and post-traumatic stress, and has achieved significant therapeutic effects. However, its specific mechanism of action is still unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to link the avoidance phenotype to psychiatric disorders by utilizing the <em>Caenorhabditis elegans</em> as a biological model, revealing the potential common mechanisms underlying the treatment of these disorders with <em>Shen Qi</em> pills.</div></div><div><h3>Methods</h3><div>Avoidance behavior and immunity of <em>C. elegans</em> as a phenotypic entry point to explore the molecular mechanisms by which <em>Shen Qi</em> pills affects avoidance behavior with the help of <em>pmk-1</em> and <em>daf-16</em> mutants and RNA interference techniques.</div></div><div><h3>Results</h3><div>We found that the intervention of <em>Shen Qi</em> pills can delay the avoidance behavior of <em>C. elegans</em> to <em>P. aeruginosa</em>, improve the immunity level, and reduce the up-regulation of <em>pmk-1</em> and <em>daf-16</em> genes induced by <em>P. aeruginosa. Shen Qi</em> pills did not improve the immunity of <em>pmk-1</em> mutant but could still enhance the immunity of <em>daf-16</em> mutant. After daf-16 knockout, <em>Shen Qi</em> pills could not delay its avoidance behavior, which was consistent with the results shown in the neuron-specific silencing of <em>daf-16 C. elegans</em>.</div></div><div><h3>Conclusion</h3><div>These findings reveal the conclusion that <em>Shen Qi</em> pills regulate the avoidance behavior of <em>C. elegans</em> induced by <em>P. aeruginosa</em> via PMK-1 and DAF-16, with the latter acting directly on neurons independent of immune pathways.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156585"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549435","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":"Unveiling the role of mast cells in breast cancer–a case study of natural product Eriocalyxin B as an inhibitor","authors":"Leilei Gou ,&nbsp;Grace Gar-Lee Yue ,&nbsp;Ben Chung-Lap Chan ,&nbsp;Alaster Hang-Yung Lau ,&nbsp;Pema Tenzin Puno ,&nbsp;Clara Bik-San Lau","doi":"10.1016/j.phymed.2025.156596","DOIUrl":"10.1016/j.phymed.2025.156596","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation and breast cancer are closely associated. Considering that mast cells are essential component of inflammatory cells, its relationship with breast cancer arose rising attention.</div></div><div><h3>Purpose</h3><div>This study aims to elucidate the influence of mast cells on triple negative breast cancer (TNBC) and explore potential therapeutic interventions targeting mast cells.</div></div><div><h3>Methods</h3><div>The study employed proteomic analysis and molecular investigations to examine disparities between mast cells from healthy mice and those from breast tumor-bearing mice. Additionally, the natural product Ericalyxin B (Eri B) was utilized for its anti-inflammatory and anti-breast cancer properties. <em>Ex vivo</em> and <em>in vivo</em> treatments of Eri B were conducted to assess its impact on mast cell-mediated promotion of breast cancer.</div></div><div><h3>Results</h3><div>The crosstalk between mast cells and TNBC cells was found to enhance proliferation, invasion, and migration of TNBC cells. Mast cells from breast tumor-bearing mice exhibited disparities compared to those from healthy mice, as confirmed by proteomic analysis. Treatment with Eri B suppressed the promoting effect of mast cells on breast cancer by inhibiting the TAK1/NF-κB signaling pathway and downregulating downstream cytokine release. <em>In vivo</em> treatment with Eri B also reduced mast cell numbers and tryptase levels in tumors.</div></div><div><h3>Conclusion</h3><div>This is the first study to compare disparities between mast cells derived from healthy mice and those from breast tumor-bearing mice, while also revealing the effects of the natural product Eri B on mast cells in breast cancer. Our findings highlighted the crucial role of mast cells as potential targets for triple negative breast cancer therapy and suggests that Eri B holds promise in suppressing breast cancer progression by regulating mast cells.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156596"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550272","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":"Liensinine overcomes EGFR-TKI resistance in lung adenocarcinoma through DRP1-mediated autophagy","authors":"Yuling Chen ,&nbsp;Chenying Shu ,&nbsp;Zhaowei Yan ,&nbsp;Saiqun Zhang ,&nbsp;Weijie Zhang ,&nbsp;Jian Zhao ,&nbsp;Anqi Wang ,&nbsp;Jianjun Li ,&nbsp;Yuanyuan Zeng ,&nbsp;Jianjie Zhu ,&nbsp;Jian-an Huang ,&nbsp;Zeyi Liu","doi":"10.1016/j.phymed.2025.156593","DOIUrl":"10.1016/j.phymed.2025.156593","url":null,"abstract":"<div><h3>Introduction</h3><div>Persistent upregulation of autophagy contributes to tumour cells’ resistance to EGFR-TKI therapy, and hence, inhibiting autophagy could be a valuable strategy for overcoming such resistance.</div></div><div><h3>Objectives</h3><div>This study investigated the effects of liensinine in EGFR-TKI resistant lung adenocarcinoma (LUAD) and to explore the underlying mechanism.</div></div><div><h3>Methods</h3><div>CCK-8 assay, colony formation, EdU assay and apoptosis assays were conducted for investigating the effect of EGFR-TKI and liensinine combination treatment in LUAD. Furthermore, autophagic flux were detected by western blot, fluorescence assays and TEM. In addition, by employing a DARTS approach, a CETSA assay, and SPR analysis, we identified DRP1 as a target of liensinine. Finally, by establishing a xenograft model of the disease, the impact of combination treatment <em>in vivo</em> was assessed.</div></div><div><h3>Result</h3><div><em>In vitro</em> and <em>in vivo</em> experiments revealed that the novel autophagy inhibitor liensinine enhanced the sensitivity of LUAD to EGFR-TKIs. This effect was achieved by inhibiting autophagic flux. We then examined whether liensinine inhibits autophagic flux through the impairment of autophagosome and autolysosome degradation. Furthermore, we identified DRP1 as a target of liensinine. The activation of DRP1 by liensinine through dephosphorylation at Ser637 promotes the accumulation of autophagosomes and autolysosomes while simultaneously blocking autophagic flux, thereby enhancing the cancer cell-killing effects of EGFR-TKIs.</div></div><div><h3>Conclusions</h3><div>Our study validated the efficacy of liensinine in overcoming EGFR-TKI resistance and elucidated the mechanism underlying liensinine's inhibition of autophagy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156593"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550273","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":"Edaravone dexborneol exerts anti-epileptic effects on rodent temporal lobe epilepsy by promoting NMDAR deactivation and inhibiting oxidative stress","authors":"Wanhua Qiu ,&nbsp;Roumeng Chen ,&nbsp;Lechen Pan ,&nbsp;Yiqian Li ,&nbsp;Yuchen Xu ,&nbsp;Yuqian Li ,&nbsp;Ang Guo ,&nbsp;Wenting Huang ,&nbsp;Tao Tan ,&nbsp;Peijun Li ,&nbsp;Chenglong Xie ,&nbsp;Huiqin Xu ,&nbsp;Li Lin ,&nbsp;Xinshi Wang","doi":"10.1016/j.phymed.2025.156558","DOIUrl":"10.1016/j.phymed.2025.156558","url":null,"abstract":"<div><h3>Background</h3><div>Disease-modifying treatments with anti-epileptic effects are currently unavailable and urgently required for temporal lobe epilepsy (TLE). Combined therapy targeting multiple mechanisms may offer a promising anti-epileptic strategy, given the complex processes underlying epileptogenesis.</div></div><div><h3>Purpose</h3><div>This study evaluates the effects of Edaravone Dexbroneol, a combination of Edaravone and Dexborneol in 4:1, on rat and mouse TLE models and an in vitro epileptiform activity model.</div></div><div><h3>Methods</h3><div>The Pilocarpine-induced rat TLE model and the Kainic acid-induced mouse TLE model were used to assess the in vivo effect of Edaravone and/or Dexbornel. Primary neurons were utilized to evaluate the in vitro effect of drugs using calcium imaging, electrophysiological and biochemical analyses, as well as RNA sequencing.</div></div><div><h3>Results</h3><div>Treatment of Edaravone Dexbornel during the latent period significantly alleviated epileptic seizures in rodents, mitigated cognitive impairment, and inhibited neuronal loss and astrocytic activation. In vitro, Edaravone Dexborneol inhibited the action potentials and protected primary hippocampal neurons from Mg²⁺-free-induced neurite injury. All these effects were significantly more pronounced in the group treated with the Edaravone Dexborneol mixture compared to either drug used individually. Furthermore, Edaravone can significantly inhibit Mg²⁺-free-induced calcium oscillations in primary neurons, probably by promoting the deactivation of NMDA receptors. RNA sequencing and RT-PCR analysis revealed that synergetic regulation of lipid metabolism, oxidative stress, apoptosis, and calcium signaling probably underlay the neuroprotective effect of Edaravone Dexbornel on epileptic neurons.</div></div><div><h3>Conclusion</h3><div>Edaravone Dexborneol exhibits antiepileptic effects and may fill the gap in disease-modifying treatments for TLE.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156558"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550270","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":"Ginseng in delaying brain aging: Progress and Perspectives","authors":"Jingwen Niu ,&nbsp;Guoqi Zhu ,&nbsp;Junjie Zhang","doi":"10.1016/j.phymed.2025.156587","DOIUrl":"10.1016/j.phymed.2025.156587","url":null,"abstract":"<div><h3>Background</h3><div>The <em>Shennong Bencao Jing</em> (Shennong's Classic of Materia Medica) records that <em>Panax ginseng</em> C. A. Mey (ginseng) ‘lightens the body and prolongs life’. Many investigations have documented that ginseng exerts neuroprotective effects by mitigating the aging of the brain. However, a comprehensive review of the impacts of ginseng on brain aging remains lacking.</div></div><div><h3>Purpose</h3><div>This study aims to review the advances in ginseng research regarding its role in delaying brain aging, focusing on its bioactive constituents, underlying mechanisms and potential side effects. The findings provide scientific pieces of evidence to support the medical utilization of ginseng in the delaying senescence and the management of aging-related diseases.</div></div><div><h3>Methods</h3><div>This review includes studies on ginseng and brain aging in humans, retrieved from English-language research articles published between 2017 and the present in the PubMed and Web of Science databases. The work focused on ginseng, brain aging, and aging-related diseases, utilizing keywords such as “Ginseng”, “Brain aging”, “central nervous system”, “intracellular homeostasis”, “peripheral system”, <em>etc</em>.</div></div><div><h3>Results</h3><div>Ginseng comprises a varied spectrum of biologically bioactive constituents, such as ginsenosides, Maillard reaction products, ginseng polysaccharides, volatile oils, amino acids, proteins, <em>etc</em>. These components work to contribute to their significant medicinal value. Based on the traditional Chinese medicine (TCM) theory that “the heart and brain are interconnected, the liver and brain are mutually supportive, the brain and spleen are related, the brain and lung are linked, and the brain and kidney work in harmony,” we summarize that ginseng may sustain neural homeostasis through both central and peripheral perspectives. Additionally, the potential toxic side effects of ginseng are minimal.</div></div><div><h3>Conclusion</h3><div>Ginseng and its bioactive constituents exhibit considerable promise in delaying brain aging and treating neurodegenerative diseases. Future research should prioritize exploring the direct targets of ginseng and its active ingredients, and work toward establishing precise drug-target-efficacy relationships. This approach will facilitate the translation of these findings into clinically viable therapeutic approaches.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156587"},"PeriodicalIF":6.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549432","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}