Phytomedicine最新文献

{"title":"Pelargonium sidoides - from ethnopharmacology to evidence-based medicine: a systematic review","authors":"Oksana Honchar ,&nbsp;Olha Мykhailenko ,&nbsp;Olha Holovchenko ,&nbsp;Victoriya Georgiyants","doi":"10.1016/j.phymed.2026.157880","DOIUrl":"10.1016/j.phymed.2026.157880","url":null,"abstract":"<div><h3>Background</h3><div><em>Pelargonium sidoides</em> DC. (Geraniaceae) has a long history of traditional use among indigenous peoples of Southern Africa for treating respiratory and gastrointestinal disorders. Its transformation into the modern pharmaceutical product Umckaloabo (EPs® 7630) exemplifies the transition from traditional medicine to evidence-based therapeutics.</div></div><div><h3>Purpose</h3><div>To provide a systematic analysis of <em>P. sidoides</em>, spanning from its botanical characteristics and ethnobotanical roots to its development as a regulated phytomedicine. The review focuses on the plant's unique phytochemical profile and provides a detailed synthesis of its molecular and systems-biological mechanisms of action, cultivation sustainability, and clinical efficacy in managing respiratory tract infections.</div></div><div><h3>Study design and methods</h3><div>A systematic search was conducted across PubMed, Scopus, and Cochrane Library up to December 2025 following PRISMA guidelines. Sources included scientific articles, pharmacopoeias, patents, and ethnobotanical records in English and Ukrainian.</div></div><div><h3>Results</h3><div>The systematic synthesis of identified records characterizes the chemical diversity of <em>P. sidoides</em>, focusing on specialized metabolites such as highly substituted benzopyranones, prodelphinidins, and unique coumarin sulfates. The review discusses modern cultivation practices, sustainability issues, and comparative extraction techniques, while analytical methods such as HPLC, LC-MS, and TLC for standardization are summarized. The pharmacological profile is defined by multi-target activity, encompassing immunomodulatory, antibacterial, and antiviral effects, including studies on SARS-CoV-2 and other respiratory pathogens. Analysis of available clinical data validates the therapeutic use of <em>P. sidoides</em> root preparations for managing acute bronchitis, rhinosinusitis, and tonsillopharyngitis.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that the integration of <em>P. sidoides</em> into modern healthcare is supported by the synergy between traditional knowledge and molecular and clinical validation. By mapping the developmental trajectory — from wild harvesting to systems-biological evidence — this review identifies <em>P. sidoides</em> as a model for the pharmaceutical tran<strong>s</strong>lation of ethnobotanical resources into standardized, evidence-based phytomedicines.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157880"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137824","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":"DDX17 acts as a target of Buddlejasaponin IVb ameliorating dopaminergic neuron iron metabolism dysregulation in Parkinson’s disease","authors":"Qiang-Ming Li ,&nbsp;Man-Lei Zhu ,&nbsp;Xiang Li ,&nbsp;Jing-Xing He ,&nbsp;Xue-Qiang Zha ,&nbsp;Jian-Ping Luo ,&nbsp;Feng-Yun Zhang","doi":"10.1016/j.phymed.2026.157938","DOIUrl":"10.1016/j.phymed.2026.157938","url":null,"abstract":"<div><h3>Background</h3><div>Identifying novel targets that ameliorating dopaminergic neuron iron metabolism dysregulation may provide potential therapeutic strategies for Parkinson’s disease (PD). Buddlejasaponin IVb (BJP-IVb) is the first natural product that can ameliorate iron regulatory protein 2 (IRP2)-mediated iron metabolism dysregulation in dopaminergic neuron to suppress PD. BJP-IVb may exert this bioactivity through novel target. However, the pharmacological target of BJP-IVb is unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to discovery the potential novel target of BJP-IVb ameliorating dopaminergic neuron iron metabolism dysregulation in PD.</div></div><div><h3>Method</h3><div>BJP-IVb probe (BJP-IVb-P) were synthesized to identify the potential novel target by affinity-based protein profiling. The expression of DEAD-box helicase 17 (DDX17) was knocked down in vitro and in vivo to prove the potential novel target of BJP-IVb is DDX17.</div></div><div><h3>Results</h3><div>We proved that BJP-IVb could directly bind to DDX17. Dopaminergic neurons exhibit an elevated expression of DDX17 in PD. Dopaminergic neuron iron metabolism dysregulation and Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) signaling pathway activation in PD could be alleviated by the knockdown of DDX17 in vitro and in vivo. The inhibitory effect of BJP-IVb on dopaminergic neuron iron metabolism dysregulation and JAK2–STAT5 signaling pathway activation in PD could be abolished by the knockdown of DDX17 in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>This study first proved that DDX17 is a pharmacological target for ameliorating dopaminergic neuron iron metabolism dysregulation in PD, and BJP-IVb ameliorates dopaminergic neuron iron metabolism dysregulation by targeting DDX17.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157938"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192104","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":"Stress endurance mediates the healthspan-promoting effect of two newly described iridoid glycosides from Verbascum nigrum ssp. abietinum in Caenorhabditis elegans","authors":"Slaveya Krustanova ,&nbsp;Monika N. Todorova ,&nbsp;Vanya Gerasimova ,&nbsp;Martina S. Savova ,&nbsp;Stoyan Stoyanov ,&nbsp;Milena P. Popova ,&nbsp;Milen I. Georgiev ,&nbsp;Kalina Alipieva","doi":"10.1016/j.phymed.2026.157944","DOIUrl":"10.1016/j.phymed.2026.157944","url":null,"abstract":"<div><h3>Background</h3><div>Natural products are emerging as promising options for promoting health and managing age-related diseases. Iridoid glycosides, a diverse class of monoterpenoids, exert multiple beneficial effects and are of significant interest in pharmaceutical research. They are abundant in Scrophulariaceae, particularly in the genus <em>Verbascum</em> L. (mulleins). However, the infraspecific taxon <em>V. nigrum</em> ssp. <em>abietinum</em> (Borbas) I.K. Ferguson, native to the Balkan Peninsula, has not been previously investigated regarding chemical composition or healthspan-modulating potential.</div></div><div><h3>Purpose</h3><div>This study aimed to isolate and characterize the main secondary metabolites of <em>V. nigrum</em> ssp. <em>abietinum</em> and to evaluate the effects of iridoid glycosides on age-related physiological changes and stress tolerance in <em>Caenorhabditis elegans</em>. We focused on two newly isolated sinuatol derivatives (<strong>1</strong> and <strong>2</strong>) and their influence on conserved molecular networks regulating stress response and aging.</div></div><div><h3>Methods</h3><div>Following isolation and identification of compounds <strong>1</strong> and <strong>2</strong>, phenotypic analyses were conducted to assess toxicity, lifespan, physiology, and stress resistance. Basal metabolism and molecular mechanisms were further examined.</div></div><div><h3>Results</h3><div>Methanol extract of aerial parts of <em>V. nigrum</em> ssp. <em>abietinum</em> yielded two previously undescribed iridoid glycosides (<strong>1</strong> and <strong>2</strong>) along with twelve known constituents. Both compounds upregulated <em>sek-1</em>/p38 (MAPK) and <em>sqst-1/</em>p62 (SQSTM1), indicating enhanced autophagy and stress response. Additionally, <em>sgk-1</em>/SGK-1, <em>hsf-1</em>/HSF1, and <em>tcer-1</em>/TCERG1 were consistently overexpressed, suggesting improved oxidative stress defense, heat shock response, and transcriptional regulation. Notably, the selective upregulation of <em>hsp-16.1</em> and <em>hsp-16.2</em> upon supplementation with compound <strong>1</strong> suggests a stereospecific interaction with the HSP network, potentially linked to the positional arrangement of the caffeoyl moiety.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence that iridoid glycosides <strong>1</strong> and <strong>2</strong> from <em>V. nigrum</em> ssp. <em>abietinum</em> promote <em>C. elegans</em> healthspan by enhancing stress response through modulation of genes related to autophagy and inflammation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157944"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192384","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":"Zinc-doped carbon dots from natural Isatis Indigotica folium and calamine: SOD/CAT-mimetic activity targets ROS-Ca²⁺-NLRP3 axis for psoriatic dermatitis therapy.","authors":"Xinrong Tian, Yan Huang, Chenxin He, Ertong Dai, Xiwen Zhang, Peng Zou, Ruiyan Liu, Minlong Xia, Zixuan Lu, Bilin Jin, Siqi Wang, Yue Zhang, Hui Kong, Huihua Qu, Yan Zhao","doi":"10.1016/j.phymed.2026.158013","DOIUrl":"10.1016/j.phymed.2026.158013","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory cutaneous disorder characterized by immune dysregulation and aberrant keratinocyte proliferation, necessitating novel effective anti-inflammatory therapies.</p><p><strong>Purpose: </strong>This study synthesized zinc-doped carbon dots (IF+Zn-CDs) from Isatis indigotica Folium and calamine, investigating their therapeutic potential and underlying molecular mechanisms in psoriasis treatment.</p><p><strong>Study design: </strong>A bottom-up approach prepared IF+Zn-CDs for systematic physicochemical characterization. Their efficacy was assessed in an IMQ-induced murine psoriasis model, with anti-inflammatory mechanisms explored via transcriptomic and mechanistic assays.</p><p><strong>Methods: </strong>IF+Zn-CDs were synthesized via bottom-up using the two precursors, characterized by TEM, FTIR, and XPS. An IMQ-induced model evaluated in vivo efficacy; transcriptomic analysis identified modulated pathways, and ROS/intracellular calcium levels clarified NLRP3 regulation, with pyroptosis and MAPK/NF-κB effects validated.</p><p><strong>Results: </strong>The as-synthesized IF+Zn-CDs exhibited a uniform size distribution, excellent dispersibility, high crystallinity, and superior biocompatibility. In the IMQ-induced murine model of psoriasis, IF+Zn-CDs markedly attenuated psoriatic manifestations including erythema, scaling, epidermal hyperplasia, and inflammatory cell infiltration. Transcriptomic analysis revealed that IF+Zn-CDs modulate multiple signaling pathways associated with psoriatic inflammation. Mechanistic investigations confirmed that IF+Zn-CDs inhibit NLRP3 inflammasome activation through the reduction of ROS production and intracellular calcium levels, and further suppress pyroptosis while blocking the MAPK/NF-κB signaling pathway, ultimately ameliorating psoriasiform dermatitis.</p><p><strong>Conclusion: </strong>IF+Zn-CDs have potent anti-inflammatory activities and ameliorate psoriasiform dermatitis, highlighting their promising potential as novel anti-inflammatory agents for psoriasis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"158013"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355979","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":"Exosomal miR-10b derived from protocatechuic acid-treated efferocytic macrophages inhibits endothelial inflammation by targeting MAP3K7/β-TrCP/NF-κB signaling pathway","authors":"Qing Li ,&nbsp;Shasha Zhu ,&nbsp;Guanyu Chen ,&nbsp;Yushi Du ,&nbsp;Honghui Guo ,&nbsp;Tangbin Zou ,&nbsp;Wenhua Ling ,&nbsp;Dongliang Wang","doi":"10.1016/j.phymed.2026.157939","DOIUrl":"10.1016/j.phymed.2026.157939","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Protocatechuic acid (PCA), a natural compound found in a variety of Chinese herbal medicines and plant foods, has been documented to inhibit atherosclerosis partially by reducing inflammation burden in arterial endothelial cells. Interestingly, &lt;em&gt;in vitro&lt;/em&gt; studies showed that PCA at physiologically reachable concentrations does not affect inflammation burden in TNF-α-stimulated aortic endothelial cells, whereas it increases the content of exosomal miR-10b secreted by macrophages that have engulfed apoptotic cells (efferocytic macrophages).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study was aimed at investigating whether the &lt;em&gt;in vivo&lt;/em&gt; anti-inflammatory effect of PCA in arterial endothelial cells was due to the uptake of efferocytic macrophage exosomal miR-10b.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A transwell co-culture system of aortic endothelial cells with efferocytic macrophages was used to evaluate the effect of PCA on NF-κB-mediated inflammation in aortic endothelial cells. An inhibitor of exosome secretion, GW4869, was applied to confirm the role of exosomes played in the anti-inflammatory effect of PCA. The aortic endothelial cells were administrated with exosomes isolated from PCA-treated efferocytic macrophages or miR-10b mimic or antagomir to ascertain the role of miR-10b in downregulating inflammation effect of PCA. Bioinformatics analyses, loss-of- and gain-of-function assays and luciferase reporter gene assays were performed to identify targeting relationship between miR-10b and mitogen-activated protein kinase kinase kinase 7 (MAP3K7)/β-transducin repeat-containing protein (β-TrCP). Besides, &lt;em&gt;Apoe&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice with advanced atherosclerotic plaques were subjected to intragastric administration of PCA and intraperitoneal injection of GW4869. The miR-10b/MAP3K7/β-TrCP/NF-κB signaling pathways and inflammation indicators were determined &lt;em&gt;in vivo&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;PCA at physiologically reachable concentrations inhibited NF-κB-mediated inflammation in TNF-α-stimulated aortic endothelial cells co-cultured with efferocytic macrophages, in which treatment of GW4869 reversed this effect. Exosomes isolated from PCA-treated efferocytic macrophages inhibited inflammation and increased miR-10b levels in aortic endothelial cells. Mechanistically, exosomal miR-10b post-transcriptionally repressed MAP3K7 and β-TrCP, both of which promote NF-κB activation. Knockdown of &lt;em&gt;Map3k7&lt;/em&gt; and &lt;em&gt;Btrc&lt;/em&gt; with siRNA in aortic endothelial cells abolished the inhibitory effects of exosomes isolated from PCA-treated efferocytic macrophages on NF-κB-mediated inflammation. Consistently, oral administration of PCA increased miR-10b level and inhibited &lt;em&gt;Map3k7&lt;/em&gt; and &lt;em&gt;Btrc&lt;/em&gt; mRNA expression as well as inflammation in aortic endothelial cells in &lt;em&gt;Apoe&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice, all of which were abrogated by GW4869 co-treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;d","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157939"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181832","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":"A molecular perspective on cardioprotective potential of Moringa oleifera Lam. and its nano-formulations","authors":"Punniyakoti Veeraveedu Thanikachalam ,&nbsp;Poojitha Mallapu ,&nbsp;Vidhya Varshini Dhalapathy ,&nbsp;Mohamed Ishaq Hydar ,&nbsp;Karthika Ramesh ,&nbsp;Srinivasan Ramamurthy ,&nbsp;Pavithra Bharathy","doi":"10.1016/j.phymed.2026.157867","DOIUrl":"10.1016/j.phymed.2026.157867","url":null,"abstract":"<div><h3>Background</h3><div><em>Moringa oleifera</em> Lam. (Family: Moringaceae) possesses diverse pharmacological properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, neuroprotective, and cardioprotective effects. Despite growing evidence of its cardiovascular benefits, a comprehensive synthesis of the molecular mechanisms involved in cardiovascular diseases (CVDs) is lacking.</div></div><div><h3>Purpose</h3><div>This review aims to consolidate existing evidence on the molecular mechanisms underlying the cardioprotective effects of <em>Moringa oleifera</em> Lam. and its nanoformulations, thereby providing a framework for future investigations in CVD therapy.</div></div><div><h3>Methods</h3><div>Relevant literature published between 2015 and 2025 on the cardioprotective activities of <em>Moringa oleifera</em> Lam. was systematically retrieved from major scientific databases, including ScienceDirect, PubMed, Springer, Taylor &amp; Francis, and Web of Science.</div></div><div><h3>Results</h3><div>A comprehensive review of literature from 2015 to 2025 identified 89 <em>in vivo</em>, 24 <em>in vitro</em>, 8 clinical, and 6 nanoformulation studies, addressing major cardiovascular conditions. Leaves were the most studied plant part (78%), mainly as aqueous and ethanolic extracts. Key bioactives included flavonoids (quercetin, kaempferol), glucosinolates, and isothiocyanates. Cardioprotection was mediated through modulation of multiple pathways, NF-κB, Nrf2/Keap1, PI3K/Akt, PPAR, AMPK, and MAPK. Nanoformulation-based delivery systems demonstrated superior bioavailability and enhanced cardioprotective efficacy at lower doses compared to crude extracts. Clinical trials reported significant improvements in blood pressure, lipid profiles, and oxidative stress markers, although the rigour and sample sizes varied considerably.</div></div><div><h3>Conclusion</h3><div><em>Moringa oleifera</em> Lam. exhibits strong cardioprotective potential, and nanoformulation-based delivery systems further augment its therapeutic efficacy. While preclinical evidence is encouraging, rigorously designed clinical studies are urgently required to validate its safety, effectiveness, and translational value in CVD management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157867"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181903","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":"Plant-derived bioactive compounds modulate the gut microbiota in Alzheimer’s disease: Metabolite signaling, neuroimmune circuits, and systems-level regulation","authors":"Dong Xue ,&nbsp;Xixi Hu ,&nbsp;Ranchang Li ,&nbsp;Tongyu Sun ,&nbsp;Siying Qian ,&nbsp;Fuxin Chu ,&nbsp;Huawu Gao ,&nbsp;Feng Li ,&nbsp;Biao Cai","doi":"10.1016/j.phymed.2026.157919","DOIUrl":"10.1016/j.phymed.2026.157919","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is increasingly recognized as a multisystem disorder shaped not only by central neurodegeneration but also by peripheral metabolic and immune dysregulation. Growing evidence highlights the gut microbiota and its metabolites as key modulators of amyloid accumulation, tau phosphorylation, neuroinflammation, and microglial dysfunction.</div></div><div><h3>Purpose</h3><div>This review aims to synthesize current advances on how plant-derived bioactive compounds modulate AD pathophysiology through microbiota-dependent metabolic and neuroimmune mechanisms, and to establish a systems-level framework linking botanical interventions to gut microbiota remodeling and metabolite signaling.</div></div><div><h3>Methods</h3><div>A comprehensive literature survey was conducted using PubMed, Web of Science, ScienceDirect, and Google Scholar, covering publications from 2010 to 2026. Studies investigating gut microbiota, microbial metabolites, and plant-derived bioactive compounds in AD-related metabolic, immune, and neurodegenerative pathways were systematically reviewed and integrated.</div></div><div><h3>Results</h3><div>Plant-derived bioactive compounds, including phytochemicals, polysaccharides, and multi-herb formulations, interact extensively with the gut microbiota, undergoing microbial biotransformation to yield more active metabolites while simultaneously reshaping microbial community structure and metabolite profiles. These bidirectional interactions position the microbiota as a central mediator of plant-derived therapeutic activity. We summarize current evidence on how plant-derived compounds influence AD pathophysiology through microbiota-dependent metabolic and neuroimmune pathways. Major microbial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids (BAs), and indole derivatives, are discussed, together with their regulatory roles in signaling networks such as nuclear factor κB (NF-κB), phosphatidylinositol 3-kinase/Akt (PI3K/Akt), cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF), and triggering receptor expressed on myeloid cells 2 (TREM2)-associated microglial states. We further summarize evidence for synergistic strategies combining plant bioactives with probiotics and highlight advances in microbial biotransformation, precision metabolite modulation, and engineered microbial systems. Finally, future directions integrating multi-omics, personalized microbiota-guided interventions, and synthetic biology are outlined to support the development of targeted, mechanism-based therapies.</div></div><div><h3>Conclusion</h3><div>By framing AD through a gut microbiota-centered perspective, this review provides a unified mechanistic foundation for the development of next-generation interventions based on plant-derived compounds and microbiota regulation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157919"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181867","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":"Baitouweng decoction regulates ferroptosis-mediated mitophagy and apoptosis through the SLC7A11/GPX4/FTH1 pathway in ulcerative colitis","authors":"Liuliang Zhang ,&nbsp;Xiaolan Zhu ,&nbsp;Xiaochao Hu ,&nbsp;Hui Feng ,&nbsp;Guoqing Wang ,&nbsp;Ying Zhang ,&nbsp;Xuan Wang ,&nbsp;Jiayu Su ,&nbsp;Tongtong Liu ,&nbsp;Xingyue Du ,&nbsp;Huimin Zhu ,&nbsp;Limei Gu ,&nbsp;E-Hu Liu ,&nbsp;Shijia Liu","doi":"10.1016/j.phymed.2026.157898","DOIUrl":"10.1016/j.phymed.2026.157898","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of ulcerative colitis (UC) has increased recently, with severe cases potentially progressing to colon cancer. The classic herbal formula Baitouweng Decoction (BTW) has a centuries-long clinical application in UC treatment, but its underlying mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate BTW’s efficacy against Dextran Sodium Sulfate (DSS)-induced UC and clarify its mechanisms.</div></div><div><h3>Results</h3><div>Proteomic analysis identified ferroptosis as a key pathogenic mechanism in UC. <em>In vitro</em> and <em>in vivo</em> experiments showed that BTW reduced UC-associated inflammatory symptoms, normalized the levels of inflammatory factors, and maintained intestinal barrier integrity. Notably, BTW inhibited ferroptosis and restored the antioxidant capacity of the SCL7A11/GSH/GPX4 system, thereby suppressing UC inflammation. Transcriptomic analysis revealed apoptosis and ferroptosis as core pathways for BTW’s intervention in UC, with mitophagy serving as a pivotal hub connecting these processes. BTW regulated the PINK1/PARKIN-mediated mitophagy pathway and apoptosis, and this regulation was closely linked to ferroptosis.</div></div><div><h3>Conclusion</h3><div>BTW alleviates UC-related inflammation and intestinal barrier damage by modulating apoptosis, mitophagy, and ferroptosis, while mitigating oxidative stress.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157898"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116348","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":"Dieckol, a phlorotannin from Ecklonia cava, alleviates stress hormone-induced depressive-like behaviors through glucocorticoid receptor antagonism","authors":"Inhye Park ,&nbsp;Jung-Eun Lee ,&nbsp;Minji Kim ,&nbsp;Minseok Yoon ,&nbsp;Min Jung Kim ,&nbsp;Min-Sun Kim ,&nbsp;Suengmok Cho ,&nbsp;Min Young Um","doi":"10.1016/j.phymed.2026.157906","DOIUrl":"10.1016/j.phymed.2026.157906","url":null,"abstract":"<div><h3>Background</h3><div>Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from <em>Ecklonia cava</em> (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling.</div></div><div><h3>Methods</h3><div>CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches.</div></div><div><h3>Results</h3><div>PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK–CREB–BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (<em>Mkp-1, Sgk-1, Fkbp5</em>, and <em>Bdnf</em>), and restored ERK–CREB–BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels.</div></div><div><h3>Conclusion</h3><div>Collectively, our results suggest that DK, a major bioactive phlorotannin from <em>E. cava</em>, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157906"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116351","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":"Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms","authors":"Zhong-Wei Yao ,&nbsp;Yong-Qing Wang ,&nbsp;He Zhu","doi":"10.1016/j.phymed.2026.157901","DOIUrl":"10.1016/j.phymed.2026.157901","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic reprogramming is a hallmark of cancer development. By regulating energy and nutrient metabolism, it shapes an immunosuppressive tumor microenvironment (TME) that supports rapid tumor proliferation and promotes cancer progression. Ginsenosides, the major active components of <em>Panax ginseng</em>, have recently been found not only to directly inhibit tumor cell proliferation and induce apoptosis, but also to remodel the TME through metabolic regulation in both tumor and immune cells, thereby enhancing antitumor immune responses. However, the underlying mechanisms have not been fully elucidated.</div></div><div><h3>Purpose</h3><div>This study systematically summarizes the metabolic targets and regulatory mechanisms of ginsenosides in key pathways of metabolic reprogramming involving glucose, lipid, amino acid, and nucleotide metabolism, aiming to provide a theoretical basis and new perspectives for tumor metabolism-based immunotherapy.</div></div><div><h3>Methods</h3><div>Using \"ginsenoside\", \"glucose metabolism\", \"Warburg effect\", \"lipid metabolism\", \"fatty acid\", \"cholesterol\", \"amino acid metabolism\", \"nucleotide metabolism\", \" tumor\" and combinations of these keywords in PubMed, Web of Science, and CNKI.</div></div><div><h3>Results</h3><div>Ginsenosides primarily restore immune cell function by reversing the Warburg effect, suppressing fatty acid synthesis and oxidation, downregulating cholesterol and arachidonic acid metabolism, and inhibiting the depletion of glutamine and tryptophan as well as the catabolism of arginine. In addition, ginsenosides downregulate purine and pyrimidine biosynthesis, thereby limiting tumor cell proliferation.</div></div><div><h3>Conclusions</h3><div>Ginsenosides alleviate the immunosuppressive state of the TME and restore immune effector cell functions through multidimensional metabolic regulation. In the future, it is necessary to conduct further clinical investigations and develop metabolism-targeted ginsenoside delivery systems to ultimately achieve precise cancer therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157901"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116405","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}