Phytomedicine最新文献

{"title":"8-Shogaol from White Ginger induces cell apoptosis and autophagy in human colon cancer HCT116 cells and in vivo","authors":"Rui Zhang ,&nbsp;Jing-Yu Feng ,&nbsp;Kiran Thakur ,&nbsp;Fei Hu ,&nbsp;Jian-Guo Zhang ,&nbsp;Yi-Long Ma ,&nbsp;Zhao-Jun Wei","doi":"10.1016/j.phymed.2026.157954","DOIUrl":"10.1016/j.phymed.2026.157954","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) constitutes a leading global health challenge, with incidence and mortality on an upward trajectory across diverse populations. Ginger (<em>Zingiber officinale</em> Roscoe) is a widely recognized traditional medicinal plant with established therapeutic and culinary applications. 8-Shogaol, a key phenolic component of ginger, exhibits diverse pharmacological activities including antitumor, anti-inflammatory, and analgesic effects. However, its specific mechanisms against colon cancer remain incompletely understood.</div></div><div><h3>Purpose</h3><div>Our study outlines the anti-cancer efficacy of 8-Shogaol against human colon cancer HCT116 cells and its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>miRNA-omics was employed to delineate the molecular mechanisms through which 8-Shogaol induces apoptosis in HCT116 cells. <em>In vivo</em> and <em>in vitro</em> validations were conducted by flow cytometry, Immunohistochemistry, and Western blotting for cell apoptosis and autophagy.</div></div><div><h3>Results</h3><div>We identified 193 differentially expressed miRNAs (98 up-regulated, 95 down-regulated) among 1289 detected miRNAs, with KEGG pathway analysis revealing significant enrichment in the PI3K/AKT signaling pathway. <em>In vivo</em> experiments revealed that 8-Shogaol (40mg/kg) significantly suppressed tumor growth. In addition, 8-Shogaol induced cell cycle arrest exclusively at the G2/M phase and enhanced apoptotic effects in HCT116 cells by modulating key regulatory proteins (Bcl-2, Caspase 3, AKT, PI3K). 8-Shogaol also induced autophagy by regulating related proteins (LC3II/LC3I, ULK-1, Beclin-1). Mechanistic exploration suggested that 8-shogaol induced autophagy and apoptosis through inhibition of PI3K/AKT signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that 8-Shogaol exerts potent anticancer effects against colon cancer through PI3K/AKT pathway modulation, concurrently inducing apoptosis and autophagy. This study provides comprehensive mechanistic insights into the therapeutic potential of 8-Shogaol for CRC treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157954"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192290","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":"Integrated high-content bioactivity profiling for rapid annotation of neuroprotective constituents in Curcumae Radix.","authors":"Jing Cui, Jia-Jun Yang, Ling-Ling Huang, Chen-Xi Shen, Xing Wang, Hua Yang, Wen Gao","doi":"10.1016/j.phymed.2026.157966","DOIUrl":"10.1016/j.phymed.2026.157966","url":null,"abstract":"<p><strong>Background: </strong>Curcumae Radix (CR), the roots derived from multiple Curcuma species, has long been used for treating neurological disorders. However, morphological similarity and chemical heterogeneity complicate efficacy evaluation, and the systematic elucidation of its neuroprotective constituents remains limited.</p><p><strong>Objectives: </strong>To establish an integrated strategy combining high-content bioactivity profiling with untargeted chemical characterization for the systematic identification of neuroprotective compounds from four CR species (C. wenyujin, CWR; C. longa, CLR; C. kwangsiensis, CKR; C. phaeocaulis, CPR).</p><p><strong>Methods: </strong>A ponatinib-induced zebrafish ischemia model evaluated extract efficacy. Extracts were fractionated by preparative liquid chromatography to construct a component library and characterized using UHPLC-QTOF MS. Multiparametric phenotypes in OGD/R-injured PC12 cells were captured using high-content imaging (HCI). A Phenotypic Feature Mapping (PFM) approach integrated m/z features with subcellular phenotypes, generating activity-guided \"m/z-phenotype\" fingerprints. Activity Scores (AS) and Cluster Scores (CS) quantified feature-phenotype associations for annotating bioactive compounds and inferring mechanisms.</p><p><strong>Results: </strong>CR extracts reduced thrombus formation, behavioral deficits, and inflammation, with CLR showing the strongest efficacy. Based on the calculated (AS) and CS, 582, 884, 835, and 730 candidate active m/z features for CWR, CPR, CLR, and CKR were screened, respectively. Finally, a total of 69 compounds were identified. Sesquiterpenoids dominated CWR, CPR, and CKR, whereas curcuminoids were core constituents in CLR. Subcellular analysis revealed species-specific regulatory preferences: nuclear morphology (CWR), mitochondrial structure (CPR, CKR), and cytoskeletal integrity (CLR).</p><p><strong>Conclusion: </strong>The untargeted metabolomics integrated high-content screening strategy enables the rapid identification of neuroprotective compounds from four chemically distinct CR. This approach provides a scalable framework for identifying bioactive compounds and functionally annotating them in complex herbal systems.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157966"},"PeriodicalIF":11.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284738","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":"The combination of paeoniflorin and hydroxysafflor yellow A alleviated pulmonary thrombosis by inhibiting platelet-neutrophil interaction via the P-selectin-PSGL-1 signaling axis.","authors":"Ting Shang, Yue Zhang, Tao Pan, Ru Shen, Jing Chang, Zhi-Sen Zhang, Yuxin Feng","doi":"10.1016/j.phymed.2026.157995","DOIUrl":"10.1016/j.phymed.2026.157995","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome characterized by an inflammatory cytokine storm and disseminated intravascular coagulation (DIC). The interplay between platelets and neutrophils is a key driver of the thrombosis-inflammation vicious cycle in sepsis, contributing to a detrimental feedback loop that exacerbates DIC and amplifies inflammatory cytokine storm. However, limited approaches are available for specifically targeting platelet-neutrophil crosstalk in sepsis. Xuebijing injection (XBJ), clinically used as an add-on for sepsis treatment, has been shown to reduce inflammatory cytokines release and alleviate microcirculation disturbances. In this study, we formulated a novel pharmaceutical composition (C0127-2) by combining paeoniflorin and hydroxysafflor yellow A according to their contents in XBJ (the two components with the highest content), demonstrating that C0127-2 effectively prevented sepsis-induced acute lung injury (ALI) and pulmonary thrombosis. We further verified this protection was achieved by disrupting the aggregates between platelets and neutrophils. Mechanistically, C0127-2 exerted its anti-crosstalk effects between platelet and neutrophil by inhibiting the P-selectin-PSGL-1 signaling axis, a core signaling axis to mediate platelet-neutrophil interaction. Collectively, we identified the key active constituents of XBJ, paving the way for developing a novel multi-component drug with specific ingredients for sepsis treatment. And we underscored a promising therapeutic strategy for sepsis that combining anti-inflammation and anti-coagulation effects, offering a potential management for improving patient outcomes.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157995"},"PeriodicalIF":11.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322188","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":"Microbiota-dependent mechanism of Jianpiyifei II in treating experimental virus-induced acute exacerbation of chronic obstructive pulmonary disease","authors":"Xuhua Yu ,&nbsp;Huameng Li ,&nbsp;Miaona Zhang ,&nbsp;Ting Cao ,&nbsp;Zhihang Liu ,&nbsp;Ziyao Liang ,&nbsp;Jingyu Quan ,&nbsp;Long Fan ,&nbsp;Lin Lin ,&nbsp;Lei Wu","doi":"10.1016/j.phymed.2026.157891","DOIUrl":"10.1016/j.phymed.2026.157891","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Numerous studies have shown that infections caused by respiratory viruses, particularly influenza A virus, contribute to the triggering and worsening of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, targeted therapies remain lacking. Our previous research indicated that the Jianpiyifei II (JPYF II) formulation, composed of &lt;em&gt;Codonopsis pilosula, Astragalus membranaceus, Bupleurum chinense, Cimicifuga foetida, Atractylodes macrocephala, Vitex trifolia, Cynomorium songaricum, and Prunus persica&lt;/em&gt;, may serve as a potential treatment for virus-induced AECOPD, although the precise mechanisms involved remain unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This research sought to explore the effects of JPYF II on AECOPD and uncover the mechanisms driving its action.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A murine model of AECOPD was established by exposing animals to cigarette smoke and then infecting them with influenza A virus. The efficacy of JPYF II was comprehensively evaluated by assessing cell counts in bronchoalveolar lavage fluid (BALF), histopathologic changes of the lungs, lung function, Micro-CT imaging features of the lungs, and RT-qPCR analysis. Additionally, the intestinal microbiota and metabolites from cecal contents were systematically analyzed using 16S rDNA sequencing, non-targeted metabolomics, and MetOrigin metabolite traceability analysis to explore potential mechanisms of action. Furthermore, a microbiota depletion experiment was performed to demonstrate whether JPYF II's effects depend on gut microbiota. Finally, network pharmacology, western blotting, and transcriptomics analyses revealed the pathways affected by JPYF II.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This study found that JPYF II treatment notably reduced the recruitment of white blood cells in both BALF and lung tissue, mitigated pulmonary inflammation, enhanced lung function, and alleviated emphysema. JPYF II also modulated the diversity and composition of intestinal flora, partially reversing dysbiosis in AECOPD mice. It promoted the presence of beneficial bacteria and simultaneously suppressed the growth of pathogenic microbes. These changes were associated with changes in metabolites such as α-ketoglutarate, sphingolipids, and bile acids. Further studies indicated that depleting gut microbiota with antibiotics partially limited the therapeutic effects of JPYF II on AECOPD. This mechanism is associated with the suppression of the Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;JPYF II alleviated pulmonary inflammation, enhanced lung function, and reduced damage to lung structure and viral replication in a virus-induced AECOPD mouse model. The mechanisms involved the improvement of gut microbiota composition. Furthermore, JPYF II suppressed immune responses and the formation of emphysema by inhibiting the JAK-STAT signaling pathway","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157891"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166451","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":"Da-Bu-Yin-Wan rescues cognitive deficits in aging and Alzheimer’s disease models by Wnt/β-catenin-dependent restoration of lysosomal acidification","authors":"Haijun Zhang ,&nbsp;Hao Zhang ,&nbsp;Meihuan Zhao ,&nbsp;Wenjun Luo ,&nbsp;Simin Chen ,&nbsp;Ping Wang ,&nbsp;Xiao Liu ,&nbsp;Shijun Xu","doi":"10.1016/j.phymed.2026.157916","DOIUrl":"10.1016/j.phymed.2026.157916","url":null,"abstract":"<div><h3>Background</h3><div>Lysosomal acidification deficits are increasingly recognized as a convergent pathological mechanism driving both age-related cognitive decline (ARCD) and early Alzheimer's disease (AD) progression, creating a self-reinforcing cycle of cellular aging and Aβ dyshomeostasis. Despite demonstrated neuroprotective effects of Da-Bu-Yin-Wan (DBYW) in Parkinson's disease models, its therapeutic potential for lysosomal dysfunction in ARCD and AD remains an uncharted area of investigation.</div></div><div><h3>Purpose</h3><div>This present work aimed to elucidate the mechanistic basis by which DBYW mitigates both ARCD and AD pathology through functionally rescuing impaired lysosomal acidification.</div></div><div><h3>Methods</h3><div>Cell-based D-galactose and Aβ-induced in BV2 cells to study lysosomal acidification. Molecular analyses combined immunofluorescence localization studies with quantitative immunoblotting of lysosomal and Wnt signaling proteins. <em>In vivo</em>, DBYW treatment effects were systematically evaluated in both D-gal-induced and APP/PS1 transgenic models using cognitive behavioral followed by immunohistochemical and biochemical assessment of brain tissues lysosomal parameters and Wnt signaling activity.</div></div><div><h3>Results</h3><div>DBYW attenuated the mechanistic basis of ARCD and AD pathology by functionally rescuing impaired lysosomal acidification. Overexpression of β-catenin could modulate D-galactose or Aβ-induced dysregulation of the Wnt/β-catenin pathway and restore lysosomes with abnormal acidification, while DBYW could regulate lysosomal function by promoting Wnt/β-catenin signaling. In addition, in D-gal-induced aging and AD model mice, DBYW treatment activated Wnt/β-catenin signaling to restore lysosomal acidification, while spatial memory deficits in ARCD and AD models were improved, and pathology in mouse attenuation and APP/PS1 mouse brain tissue was inhibited.</div></div><div><h3>Conclusion</h3><div>DBYW shows a potential dual efficacy in improving cognitive decline in ARCD and AD models. It makes DBYW a promising disease-modifying intervention targeting the shared lysosomal pathophysiology of aging-associated neurodegeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157916"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150424","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":"Validates blood pressure control for seizure management: Jujuboside B exerts antiseizure effects via blood pressure reduction and activation of NTS-VGLUT2+ neurons","authors":"Xia Qin ,&nbsp;Wenya Zhao ,&nbsp;Siruan Chen ,&nbsp;Jiaojiao Zhao ,&nbsp;Keying Tian ,&nbsp;Han Guo ,&nbsp;Lei Yang ,&nbsp;Panpan Zhang ,&nbsp;Zuxiao Yang ,&nbsp;Nan Zhang ,&nbsp;Zhanfeng Jia ,&nbsp;Dezhi Kong ,&nbsp;Wei Zhang","doi":"10.1016/j.phymed.2026.157890","DOIUrl":"10.1016/j.phymed.2026.157890","url":null,"abstract":"<div><h3>Background</h3><div>The interaction between the cardiovascular and brain is crucial for epileptogenesis, but the underlying mechanisms are unclear. Ziziphi Spinosae Semen (ZSS), a traditional herb used for its heart-nourishing and mind-calming effects, is hypothesized to potentially suppress seizures through modulation of cardiovascular function.</div></div><div><h3>Purpose</h3><div>To explore how jujuboside B (JuB) from ZSS affects epilepsy through cardiovascular-brain crosstalk.</div></div><div><h3>Methods</h3><div>In acute seizure models, epileptic activity and cardiovascular parameters were evaluated via Electroencephalogram/ Electromyography (EEG/EMG) recording, multiphysiological signal monitoring, laser speckle blood flow imaging, and left vagotomy. Whole-brain c-Fos mapping revealed that nucleus of the solitary tract (NTS) was an activated region. Chemogenetic methods and <em>in vivo</em> multi-channel recording techniques were used to activate neurons expressing vesicular glutamate transporter 2 in NTS (NTS-VGLUT2⁺) neurons and monitor neuronal activity in the dentate gyrus (DG).</div></div><div><h3>Results</h3><div>JuB exerts both hypotensive and antiseizure effects. Sodium nitroprusside (SNP) elicited similar effects, establishing a therapeutic link between blood pressure reduction and seizure suppression. JuB increased vagal nerve discharge, and its antiseizure activity was abolished by left vagotomy. Whole-brain c-Fos mapping identified NTS and DG as key responsive regions. JuB selectively activated NTS-VGLUT2⁺ neurons, augmenting their firing. Chemogenetic activation of these neurons inhibited DG neuronal hyperactivity and suppressed pentylenetetrazole (PTZ)-induced seizures.</div></div><div><h3>Conclusion</h3><div>JuB exerts its antiseizure effect through the activation of vagal-mediated NTS-VGLUT2⁺ neurons and the inhibition of DG neurons. This reconciles cardiovascular and neurological modulation. These findings elucidate JuB’s pharmacological basis, advance epileptic pathophysiology understanding, and support personalized therapeutic strategies for epilepsy with hypertension.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157890"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143280","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":"Spatial-single cell multiomics reveals TRIM44-driven Treg differentiation and drug resistance in AML: Therapeutic reversal by Sinomenine","authors":"Zhixuan Deng ,&nbsp;Woding Deng ,&nbsp;Ning Tang ,&nbsp;Chunmei Ban ,&nbsp;Yupeng Wu ,&nbsp;Mengqi Gong ,&nbsp;Peng Wu ,&nbsp;Xuewei Bao ,&nbsp;Hao Zhou ,&nbsp;Yikao Liu ,&nbsp;Xin Wu ,&nbsp;Qiangqiang Zhao","doi":"10.1016/j.phymed.2026.157885","DOIUrl":"10.1016/j.phymed.2026.157885","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by genetic diversity. These features of AML contribute to immune evasion and therapeutic resistance. Relapse after chemotherapy remains a major clinical challenge in the management of AML. The bone marrow microenvironment is believed to play a critical role in resistance; however, the underlying mechanisms are not fully understood.</div></div><div><h3>Methods</h3><div>We combined spatial single-cell analyzes, ligand–receptor network inference, and Treg pseudotime modeling with functional genetics and pharmacology. A full experimental cascade (reverse transcription [RT]-quantitative polymerase chain reaction [qPCR], western blotting, immunofluorescence, and flow cytometry/function) and in vivo xenografts were used to validate these mechanisms. Structure-guided modeling supported the direct recognition of TRIM44 by the natural alkaloid sinomenine, complemented by cellular evidence of its on-target activity.</div></div><div><h3>Results</h3><div>Single-cell profiling revealed increased immune heterogeneity and enrichment of regulatory T cells (Tregs) in relapsed AML. TRIM44 was overexpressed during relapse and is associated with poor outcomes. Spatial mapping and trajectory analysis revealed a TRIM44-driven transition from Treg_naïve to Treg_effector, and tumor–Treg co-culture showed that TRIM44 knockdown in AML cells dampens Treg activation/effectorization. Mechanistically, TRIM44 coordinated a dual resistance program—apoptosis escape and epithelial–mesenchymal transition (EMT)-like features in leukemic blasts—converging with enhanced tumor→Treg communication. Sinomenine disrupted this TRIM44-dependent axis, suppressed Treg activity, and re-sensitized resistant AML cells to cytarabine, yielding synergistic anti-leukemic effects in vitro and efficacy in xenograft models.</div></div><div><h3>Conclusions</h3><div>This study coupled spatial single-cell multiomics with functional genetics and pharmacology to decode an immune-metabolic driver of AML relapse, providing experimental evidence that pharmacological TRIM44 blockade overturns Treg-mediated immune evasion and chemoresistance. We nominate sinomenine as a tractable TRIM44 inhibitor and propose the TRIM44–Treg axis as an actionable therapeutic entry point for precision combinations with cytarabine in relapsed AML.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157885"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137879","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":"Scutellarin-eluting stents attenuate coronary restenosis by inhibiting the abnormal proliferation and migration of vascular smooth muscle cells through suppression of NF-κB signaling.","authors":"Li Zhang, Yuting Wang, Wei Min Gao, Wencong Gao, Ruoyan Ni, Jing Cai, Renhua Yang, Zhiqiang Shen, Bo He, Yu Zhuo, Peng Chen","doi":"10.1016/j.phymed.2026.157948","DOIUrl":"10.1016/j.phymed.2026.157948","url":null,"abstract":"<p><strong>Background: </strong>Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutellarin protects vascular endothelial cells and exhibits anti-thrombotic and anti-platelet effects. Notably, our prior research demonstrated that scutellarin specifically counteracts oxidative stress-driven endothelial dysfunction, a key initiating event in restenosis. This combined evidence strongly suggests its potential against in-stent restenosis (ISR). Therefore, this study explores the efficacy of scutellarin in preventing ISR after PCI.</p><p><strong>Purpose: </strong>We investigated scutellarin, derived from Erigeron breviscapus, for its potential to prevent ISR following PCI.</p><p><strong>Study design: </strong>The efficacy and mechanism of scutellarin were evaluated using both in vivo and in vitro models.</p><p><strong>Methods: </strong>An experimental atherosclerosis model was established in APOE^-/- mice. A coronary stenosis stent model was subsequently developed in minipigs through high-fat diet and balloon induced injury. Scutellarin-eluting stents with varying doses were implanted at stenosis sites. At 28 days post-PCI, multimodal imaging (QCA, OCT, IVUS) was performed to assess anti-restenosis efficacy. Additionally, in vitro H₂O₂-induced vascular smooth muscle cells (VSMCs) were used to monitor proliferation and migration. Protein levels were measured to elucidate molecular mechanisms.</p><p><strong>Results: </strong>In APOE^-/- mice, scutellarin significantly reduced lipid deposition in aortic plaques and suppressed inflammatory responses. In the porcine model, it markedly decreased neointimal thickness, neointimal area, and restenosis rates, while inhibiting inflammation. Collectively, these two in vivo models demonstrate that scutellarin-eluting stents effectively inhibit ISR. In vitro, scutellarin suppressed VSMCs proliferation and migration and mediated a shift from necrosis to autophagy-coordinated apoptosis. Mechanistically, scutellarin-mediated suppression of the synthetic phenotype switch in VSMCs was accompanied by the coordinated downregulation of both the Pl3K/AKT and IKKs/NF-κB cascades.</p><p><strong>Conclusions: </strong>This study establishes the efficacy of scutellarin in mitigating ISR using two complementary in vivo models. Scutellarin-eluting stents in atherosclerotic minipigs overcome translational barriers through full interventional simulation. Furthermore, scutellarin inhibits VSMCs proliferation, migration and promotes autophagy-coordinated apoptosis by the coordinated downregulation of both the Pl3K/AKT and lKKs/NF-κB cascades.These findings highlight scutellarin as a promising candidate for next-generation bioactive stent coatings, bridging phytopharmacology and precision interventional cardiology.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157948"},"PeriodicalIF":11.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259040","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":"Methyl jasmonate promotes host defense by activating autophagy during Mycobacterium tuberculosis infection.","authors":"Asmita Sapkota, Young Jae Kim, Ji Woong Yu, Geumseo Kim, Bokeum Jung, Bo Eun Heo, Sang-Hee Lee, Jake Whang, Jichan Jang, Jin-Man Kim, In Soo Kim, Eun-Kyeong Jo","doi":"10.1016/j.phymed.2026.157967","DOIUrl":"10.1016/j.phymed.2026.157967","url":null,"abstract":"<p><strong>Background: </strong>Jasmonates are a class of plant hormones that play multiple roles in plant growth, development, stress responses, and antimicrobial activity. However, their role in antimicrobial responses in mammalian cells and in vivo, particularly against Mycobacterium tuberculosis (Mtb), remains unclear. Tuberculosis remains a global challenge in human health, particularly with the rise of multidrug-resistant strains. Thus, exploring novel therapeutic agents is urgently warranted. In this study, we investigated the antimicrobial effects of methyl jasmonate (MeJA) against Mtb to evaluate its potential as a novel host-directed therapy agent.</p><p><strong>Results: </strong>MeJA did not exhibit direct antimycobacterial effects; however, it induced antimicrobial responses in macrophages and in vivo against Mtb, including multidrug-resistant strains. During infection, MeJA significantly reduced the expression of proinflammatory cytokines and chemokines in both macrophages and lung tissues. Furthermore, MeJA treatment inhibits the AKT-MTOR axis, leading to increased expression of autophagy-related and lysosomal genes by promoting nuclear translocation of transcription factor EB in macrophages during M. tuberculosis infection. MeJA robustly activated autophagy, thereby enhancing phagosomal maturation and promoting antimicrobial responses.</p><p><strong>Conclusion: </strong>Together, our results provide valuable insights into the potential of MeJA for developing novel, plant-derived strategies to combat mycobacterial infections, highlighting its role in enhancing host defense mechanisms by ameliorating pathological inflammation and activating autophagy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"157967"},"PeriodicalIF":11.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271741","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":"Total flavones from Abelmoschus manihot (L.) Medik. [Malvaceae] extract ameliorates diabetic liver injury: association with ferroptosis suppression and the PI3K/AKT/Nrf2 pathway","authors":"Chao Lv ,&nbsp;Jiani Hou ,&nbsp;Hongyin Sun ,&nbsp;Wei Su ,&nbsp;Zhongsha Li ,&nbsp;Yuesong Wu ,&nbsp;Lei Wang ,&nbsp;Xiaoyong Wei ,&nbsp;Shoaib Anwaar ,&nbsp;Fangzheng Mou ,&nbsp;Darong Wei ,&nbsp;Huihong Wang ,&nbsp;Yunjin Xie ,&nbsp;Qiaohong Yang ,&nbsp;Mingzhu Yin","doi":"10.1016/j.phymed.2026.157940","DOIUrl":"10.1016/j.phymed.2026.157940","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Diabetic liver injury (DLI), a common complication of diabetes mellitus, is characterized by metabolic disturbances that induce hepatic dysfunction and histopathological alterations such as steatosis, inflammation, and fibrosis. These alterations may progress to cirrhosis with limited effective therapies. Total flavones from &lt;em&gt;Abelmoschus manihot&lt;/em&gt; (L.) Medik. [Malvaceae] extract (TFA), a traditional bioactive compound, has attracted attention due to its potent anti-inflammatory and metabolic regulatory properties. However, the capacity of TFA to ameliorate DLI and its underlying mechanism remain unknown.&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 hepatoprotective effects of TFA against DLI and to elucidate its underlying mechanism, with a particular focus on its association with the regulation of the PI3K/AKT/Nrf2 signaling pathway and ferroptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to identify TFA metabolites. DLI mouse model was established by high-fat diet (HFD) feeding and streptozotocin (STZ) injection. The mice were randomly allocated into four groups (&lt;em&gt;n&lt;/em&gt; = 8): Control, Model, TFA-L, and TFA-H. TFA was administered daily by oral gavage for 12 consecutive weeks. &lt;em&gt;In vitro&lt;/em&gt; hepatocyte model was induced with high glucose (HG) and oleic acid/palmitic acid (OA/PA). To systematically clarify the pharmacodynamic basis and molecular mechanisms underlying which TFA ameliorates DLI via inhibiting ferroptosis through the PI3K/AKT/Nrf2 pathway, integrated multi-omics strategies including network pharmacology, transcriptomics, and metabolomics were coupled with molecular docking, cellular thermal shift assay (CETSA), and experimental validations—including reactive oxygen species (ROS) detection, superoxide dismutase (SOD), glutathione (GSH), and oxidized glutathione (GSSG) determination, ferric/ferrous ion assay, and lipid peroxidation detection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 56 metabolites in TFA were identified using UHPLC-Q-Orbitrap HRMS. TFA significantly ameliorated metabolic disorders in HFD/STZ-induced DLI mice, as evidenced by reduced body weight, improved glycemic control, attenuated dyslipidemia, and decreased hepatic steatosis and injury markers (&lt;em&gt;p&lt;/em&gt; &lt;em&gt;&lt;&lt;/em&gt; 0.05). Concomitantly, histopathological and immunohistochemical analyses revealed substantial alleviation of liver damage and fibrosis. Furthermore, integrated network pharmacology, transcriptomics, and metabolomics suggested that TFA exerts multi-target effects, potentially involving the PI3K/AKT/Nrf2 pathway—an axis that regulates amino acid and lipid metabolism, while also suppressing ferroptosis-related molecular programs to mitigate metabolic and hepatic disturbances. In line with this, molecular docking and CETSA suggested po","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157940"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192655","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}