Phytomedicine最新文献

{"title":"Dihydroartemisinin promotes ABCG5/G8-mediated cholesterol efflux to potentiate anti-PD-1 therapy through YAP1-TEAD1 complex disruption in hepatocellular carcinoma.","authors":"Yuting Gao, Yi Gong, Zhimin Du, Wei Zhang, Lin Lai, Meiqi Lan, Zhuoyue Jia, Xiaoyong Song, Yajun Xiong, Yanli Gong, Yanguang Yang, Xinli Shi","doi":"10.1016/j.phymed.2026.158584","DOIUrl":"10.1016/j.phymed.2026.158584","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol accumulation influences the efficacy of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC), highlighting a targetable metabolic vulnerability. Dihydroartemisinin (DHA) has shown antitumor activity in HCC; however, its role in regulating cholesterol accumulation remains unclear.</p><p><strong>Purpose: </strong>The purpose of this study is to explore whether DHA enhances anti-PD-1 immunotherapy in HCC by promoting cholesterol efflux and to elucidate the underlying molecular mechanism.</p><p><strong>Methods: </strong>A Hepa1-6 subcutaneous tumor-bearing mouse model was established to assess the combined effect of DHA and anti-PD-1 treatment. Multiplex immunohistochemistry was performed to evaluate cytotoxic T-cell infiltration and activation in the tumor microenvironment (TME). Patient-derived organoids (PDOs) were established to evaluate the antitumor activity of DHA. The regulatory mechanism of YAP1/TEAD1 on ABCG5/G8 transcription was explored using chromatin immunoprecipitation (ChIP) qPCR, dual-luciferase reporter assays, and functional gain/loss experiments. DEN/TCPOBOP-induced primary liver tumor model with hepatocyte-specific Yap1 deletion was used to assess the effect of YAP1 deficiency on cholesterol efflux. The direct effect of DHA on the YAP1-TEAD1 interaction was assessed through co-immunoprecipitation (Co-IP) and immunofluorescence (IF) co-localization, and surface plasmon resonance (SPR) analysis.</p><p><strong>Results: </strong>DHA significantly potentiates anti-PD-1 therapy in HCC-bearing mice, accompanied by reduced serum and intratumoral total cholesterol (TC) levels and increased CD8/granzyme B double-positive signals in tumor tissues, without significant body weight loss. In parallel, ABCG5/G8-mediated cholesterol efflux reduced cholesterol accumulation and suppressed tumor growth, while enhancing cytotoxic immune activity in the TME. Mechanistically, the YAP1-TEAD1 complex directly binds to the promoter regions of ABCG5 and ABCG8 and represses their transcription, thereby limiting cholesterol efflux and promoting intracellular cholesterol accumulation in HCC cells. DHA disrupted the YAP1-TEAD1 interaction, as further supported by SPR analysis, downregulated YAP1 and TEAD1, and restored ABCG5/G8-mediated cholesterol efflux. Notably, DHA-induced ABCG5/ABCG8 upregulation, cholesterol efflux, and antitumor effects were markedly attenuated by YAP1 inhibition, supporting a YAP1-dependent mechanism. In addition, DHA suppressed the growth and viability of organoids derived from patients with HCC.</p><p><strong>Conclusion: </strong>This study reveals that DHA disrupts the YAP1-TEAD1 interaction to relieve transcriptional repression of ABCG5/G8, thereby promoting cholesterol efflux, remodeling the tumor immune microenvironment toward enhanced cytotoxic T-cell activity, and enhancing anti-PD-1 immunotherapy in HCC. These findings provide a novel mechanism for DHA as an immunomo","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158584"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579774","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":"Theaflavin alleviates thoracic aortic dissection by disrupting the interaction between microtubule affinity-regulating kinase 4 and NLRP3 to inhibit inflammasome assembly.","authors":"Xing Chen, Shuying Xu, Tianhao Gu, Jintao Qian, Junhao Zhang, Yong Deng, Zhihua Wang, Jiahui Wang, Xinglong Tang, Chuiyu Kong, Qing Zhou","doi":"10.1016/j.phymed.2026.158502","DOIUrl":"10.1016/j.phymed.2026.158502","url":null,"abstract":"<p><strong>Background: </strong>Thoracic aortic dissection (TAD) is a severe vascular disorder characterized by structural damage, where macrophage-driven inflammation and NLRP3 inflammasome activation play pivotal roles. While the broad anti-inflammatory properties of Theaflavin (TF) are known, its precise structural targets within the TAD cascade remain incompletely understood. We hypothesized that TF protects against TAD by competitively disrupting the MARK4-NLRP3 interaction, thereby suppressing macrophage pyroptosis and inflammasome assembly.</p><p><strong>Purpose: </strong>To evaluate the therapeutic efficacy of TF in preventing the progression of TAD and to systematically elucidate its precise molecular and structural targets.</p><p><strong>Methods: </strong>A β-aminopropionitrile (BAPN)-induced murine TAD model was established to evaluate the efficacy of TF in mice. For Bone marrow-derived macrophages (BMDMs) and PMA-differentiated THP-1 macrophages, LPS and ATP stimulation was applied to activate the NLRP3 inflammasome. Transcriptomic sequencing, Western blot, immunofluorescence, co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and molecular docking were used to delineate TF's targets and mechanisms.</p><p><strong>Results: </strong>TF significantly reduced BAPN-induced mortality (from 40% to 15% at 20 mg/kg/d) and attenuated aortic dilation-decreasing the diameters of the ascending aorta, arch, and descending aorta by up to 17.0%, 29.2%, and 20.0%, respectively-by suppressing pro-inflammatory cytokines in mice. Mechanistically, TF directly bound to the NLRP3 NACHT domain (Gln359/Pro365 residues) to disrupt its interaction with MARK4, blocking NLRP3 trafficking to the microtubule organizing center (MTOC) and inflammasome assembly. TF also reduced GSDMD cleavage and pyroptosis, which was reversed by MARK4 overexpression.</p><p><strong>Conclusion: </strong>TF attenuates TAD pathogenesis by structurally disrupting the spatial assembly of NLRP3, thereby inhibiting the MARK4/NLRP3/GSDMD pyroptosis axis in macrophages.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158502"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423477","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":"Inhibition of toll-like receptor 4 by allicin suppresses mitochondrial DNA-mediated inflammation and pyroptosis to alleviate myocardial ischemia-reperfusion injury.","authors":"Shichao Liang, Song Wu, Jiajie Yin, Tong Gao, Mengru Liu, Yijie Gao, Fangyuan Luo, Danni Wu, Songyuan Yu, Lin Zhao, Baofu Wang, Xianlun Li","doi":"10.1016/j.phymed.2026.158513","DOIUrl":"10.1016/j.phymed.2026.158513","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial DNA (mtDNA) leakage after myocardial ischemia/reperfusion (MI/R) injury activates inflammation and pyroptosis. Although toll-like receptor 4 (TLR4) is a known mediator of MI/R injury, its interplay with mtDNA remains unclear. This study investigates the cardioprotective mechanism of allicin, focusing on its disruption of the TLR4-mtDNA axis.</p><p><strong>Purpose: </strong>This study aimed to clarify the mechanisms of inflammatory response and pyroptosis in MI/R injury and the therapeutic targets of allicin.</p><p><strong>Methods: </strong>The cardioprotective mechanism of allicin was investigated in both in vivo and in vitro MI/R models. In Sprague-Dawley rats, different concentrations of allicin were administered pre-reperfusion. Myocardial injury, cytosolic mtDNA leakage, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3)-gasdermin D (GSDMD) pathways were assessed. Network pharmacology combined with molecular dynamics simulation identified TLR4 as a candidate signaling pathway for validation. In H9C2 cells subjected to OGD/R, the role of TLR4 in mtDNA-induced inflammatory response and pyroptosis, and the therapeutic mechanism of allicin, were studied using TLR4 agonist RS09 and inhibitor resatorvid. Myocardial injury markers, cytosolic mtDNA leakage, cGAS-STING and NLRP3-GSDMD pathway activity, and TLR4 expression were measured.</p><p><strong>Results: </strong>In vivo experiments demonstrated that allicin alleviated MI/R injury, suppressed cytosolic mtDNA leakage, and inhibited the cGAS-STING-mediated inflammatory response and the NLRP3-mediated pyroptosis pathways. Subsequent network pharmacology and molecular dynamics simulation identified TLR4 as a potential mediator of these effects. In vitro studies revealed that TLR4 activation promotes mtDNA-dependent inflammation and pyroptosis, which were effectively suppressed by allicin or TLR4 inhibition.</p><p><strong>Conclusion: </strong>TLR4 activation aggravates MI/R injury by promoting mitochondrial damage and cytosolic mtDNA leakage, which activates the pro-inflammatory (cGAS-STING) and pro-pyroptotic (NLRP3-GSDMD) pathways. Allicin protects against MI/R injury by inhibiting TLR4 activation and the subsequent mtDNA-induced pathways, thereby reducing inflammation and pyroptosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158513"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397528","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":"Deep learning of multiplexed mitochondrial morphology identified natural compound combinations against skin photoaging.","authors":"Ruiqi Zheng, Min Yu, Jihua Wei, Zuyong Zhang, Jing Wang, Anastasiia Davydova, Qingyang Yu, Sihan Jin, Can Ren, Zhenzhong Yang, Ningtao Cheng, Shujing Zhang, Yi Wang","doi":"10.1016/j.phymed.2026.158526","DOIUrl":"10.1016/j.phymed.2026.158526","url":null,"abstract":"<p><strong>Background: </strong>Skin photoaging is primarily driven by mitochondrial dysfunction. Although natural products have demonstrated protective effects against Ultraviolet (UV)-induced damage, efficient screening strategies for mitochondrial-targeting compounds remain limited. Artificial Intelligence (AI)-assisted high-content screening strategy offers a valuable approach to identify bioactive candidates and elucidate their mechanisms.</p><p><strong>Purpose: </strong>This study aimed to employe an AI-assisted high-content screening strategy to identify mitochondrial-enhancing natural compounds that prevent skin photoaging and to evaluate their protective efficacy.</p><p><strong>Methods: </strong>This study employed an AI-assisted high-content screening strategy to identify mitochondria-targeting compounds that mitigate photodamage. UVB-induced models were established in cells, zebrafish, and mice with UVB lamp irradiation. Mitochondrial morphology and function were quantified using JC-1, TMRM, and MitoTracker probes. Cell viability, SA-β-gal activity, and protein expression were assessed by CCK-8 assay, SA-β-gal staining, and Western blotting, respectively.</p><p><strong>Results: </strong>Using AI-assisted high-content screening, we identified quercetin, spermidine, adenosine, Vitamin K2, and Mirabilis jalapa extract as mitochondrial protective compounds. Two optimized combinations, CC-1 and CC-2, restored ATP production, TCA cycle flux, and mitochondrial morphology in UVB-exposed human dermal fibroblasts (HDFs), reduced SA-β-gal activity, and upregulated COLLAGEN I, LAMIN B1, and SIRT3 expression. Both combinations alleviated the UVB-induced senescence phenotype by upregulating SIRT3. In a UVB-exposed zebrafish tail amputation model, CC-2 markedly promoted fin regeneration. These findings were validated in UVB-irradiated mice, where CC-2 demonstrated superior efficacy.</p><p><strong>Conclusion: </strong>Using AI-assisted high-content screening, we formulated two optimized combinations that alleviate UVB-induced skin photoaging, with CC-2 exhibiting superior efficacy, highlighting its potential as cosmetic additive.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158526"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397556","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":"Sea buckthorn flavonoid IGRh and its metabolites delay Caenorhabditis elegans aging via SIR-2.1/DAF-16-mediated IIS and autophagy-lysosomal pathways.","authors":"Jinmei Zhao, Wenxia Dong, Juan Wei, Yumei Jiang, Zeqiang Deng, Yury A Zubarev, Yang Bi","doi":"10.1016/j.phymed.2026.158579","DOIUrl":"10.1016/j.phymed.2026.158579","url":null,"abstract":"<p><strong>Background: </strong>Isorhamnetin-3-O-glucoside-7-O-rhamnoside (IGRh) is a characteristic flavonoid in sea buckthorn leaves, yet its anti-aging potential and underlying mechanisms remain largely unexplored.</p><p><strong>Purpose: </strong>This study aimed to systematically evaluate the anti-aging effects of IGRh and elucidate its mechanistic basis using Caenorhabditis elegans.</p><p><strong>Methods: </strong>Lifespan, healthspan, stress resistance, and metabolic phenotypes were assessed in wild-type, mutant, and transgenic C. elegans strains. IGRh metabolites were profiled in vivo using UHPLC-QTOF-MS, and their interactions with SIR-2.1 were analyzed through molecular docking and molecular dynamics simulations.</p><p><strong>Results: </strong>IGRh significantly extended lifespan and improved key aging-related phenotypes, including motility, intestinal barrier integrity, muscle structure, and lipid homeostasis, without impairing reproduction. IGRh also enhanced tolerance to heat and oxidative stress by elevating superoxide dismutase (SOD) and catalase (CAT) activities and reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Mechanistically, IGRh upregulated SIR-2.1 expression and promoted nuclear translocation of the transcription factors DAF-16 and HSF-1, thereby upregulating antioxidant and proteostasis-related genes. IGRh further stimulated the autophagy-lysosomal system and mitochondrial quality control, and its longevity-promoting effects were abolished in sir-2.1, daf-16, hlh-30, bec-1, clk-1, and mev-1 mutants. Metabolomic profiling revealed that IGRh was rapidly transformed into bioactive metabolites, including isorhamnetin, isorhamnetin-3-O-glucoside (I3G), quercetin-3-O-glucoside (Q3G), protocatechuic acid, and vanillic acid, several of which persisted in vivo. Q3G showed the most favorable docking score and the highest structural stability within the SIR-2.1 binding pocket. Functional assays further demonstrated that Q3G significantly delayed aging and enhanced stress resistance in C. elegans in a sir-2.1-dependent manner. Together with the CETSA results, these findings support Q3G as a key candidate bioactive metabolite contributing to the SIR-2.1-dependent anti-aging effects of IGRh.</p><p><strong>Conclusion: </strong>IGRh and its metabolites delay aging in C. elegans by mediating SIR-2.1/DAF-16 signaling and modulating downstream IIS and autophagy-lysosomal pathways. These findings provide mechanistic insight into sea buckthorn leaf flavonoids and support their potential development as natural anti-aging interventions.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158579"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562821","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":"Quercetin alleviates MSG-induced oxidative toxicity and lifespan deterioration in Caenorhabditis elegans associated with SKN-1-gst-4 detoxification and DAF-16-dependent stress resilience.","authors":"Boya Ouyang, Quanyong Wu, Zebin Zou, Jingyimei Liang, Dominique Delmas, Hui Cao, Jesus Simal-Gandara, Jianbo Xiao","doi":"10.1016/j.phymed.2026.158556","DOIUrl":"10.1016/j.phymed.2026.158556","url":null,"abstract":"<p><strong>Background: </strong>Monosodium glutamate (MSG) is widely consumed as a dietary flavor enhancer; however, its long-term effects following developmental exposure, particularly regarding oxidative toxicity and lifespan deterioration, remain poorly understood.</p><p><strong>Purpose: </strong>This study aimed to investigate MSG-induced oxidative toxicity and lifespan deterioration following developmental exposure, and to elucidate the protective mechanisms of quercetin (Que), with a focus on detoxification and stress-response pathways.</p><p><strong>Methods: </strong>Using Caenorhabditis elegans, lifespan, locomotion, reproductive output, and stress resistance were assessed. Oxidative stress markers, including ROS, SOD, CAT, and GSH, were measured. Targeted metabolomics focusing on amino acids and TCA cycle intermediates, RNA-seq analysis, and pathway validation using a gst-4p::GFP reporter strain and daf-16(mu86) mutant were performed.</p><p><strong>Results: </strong>Developmental MSG exposure significantly shortened lifespan, impaired locomotor performance, and altered reproductive patterns without affecting body length. MSG increased ROS accumulation, reduced SOD and CAT activities, and depleted GSH, thereby decreasing resistance to heat and H₂O₂ stress. Metabolomic profiling revealed widespread depletion of amino acids and TCA cycle intermediates, suggesting alterations in energy metabolism. Transcriptomic analysis demonstrated disruption of detoxification and redox networks, particularly involving glutathione metabolism and SKN-1/Nrf2 and DAF-16/FOXO pathways. Functional analyses suggested that MSG suppressed SKN-1-gst-4-associated detoxification responses, whereas Que partially restored gst-4-associated detoxification output. Notably, Que-mediated protection against lifespan deterioration was markedly attenuated in daf-16(mu86) mutants.</p><p><strong>Conclusion: </strong>Developmental MSG exposure induces persistent oxidative toxicity and lifespan deterioration through disruption of redox homeostasis, metabolic balance, and detoxification capacity. Que partially mitigates these effects, which are associated with SKN-1-gst-4 detoxification and DAF-16-dependent stress resilience.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158556"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579861","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 single-cell and network analysis identifies SLAMF7 as a secretory mediator of the joint-lung axis in rheumatoid arthritis-associated interstitial lung disease targetable by Tanshinone IIA.","authors":"Xuan He, Qingxu Ha, Liangjing Lu, Jian Gao","doi":"10.1016/j.phymed.2026.158583","DOIUrl":"10.1016/j.phymed.2026.158583","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA). However, the immune-fibrotic mediators that bridge articular inflammation and pulmonary injury have not been fully defined. Natural products represent a promising source of multi-target therapeutics, but their therapeutic effects and mechanisms in RA-ILD remain largely unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aimed to identify key immune-related secretory proteins involved in RA-ILD and to explore potential therapeutic compounds targeting the inflammatory-fibrotic axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed an integrated bioinformatic analysis using transcriptomic datasets from RA synovial tissues, RA peripheral blood mononuclear cells (PBMCs), and ILD lung tissues. RA-associated differentially expressed secretory proteins and ILD lung key genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Shared candidate genes were further prioritized using LASSO regression, support vector machine-recursive feature elimination (SVM-RFE), and external validation in an independent RA-ILD dataset. Protein-protein interaction (PPI) network analysis and functional enrichment were used to define a shared inflammatory program and guide compound prediction. Tanshinone IIA (TANIIA) was prioritized for experimental validation. Serum ELISA, collagen-induced arthritis (CIA) mouse studies, histology, flow cytometry, immunofluorescence, single-cell RNA sequencing analysis, macrophage-fibroblast co-culture, western blotting, and cellular thermal shift assay (CETSA) were used to validate molecular and pharmacological findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;SLAMF7 was identified as the sole hub gene converging RA-associated secretory proteins, ILD-related key genes, and RA-ILD differential expression signatures, exhibiting strong diagnostic performance and significantly elevated serum levels in RA-ILD patients. Network analysis identified a broader inflammatory hub-gene program enriched in TNF, chemokine, and IL-17 signaling pathways, with SLAMF7 linked to this network. TANIIA was prioritized as a candidate compound and showed favorable docking affinity to multiple hub-gene targets. In CIA mice, TANIIA alleviated arthritis, reduced circulating inflammatory and profibrotic mediators, downregulated SLAMF7 expression, and attenuated pulmonary fibrosis and macrophage infiltration. scRNA-seq revealed that SLAMF7 was enriched in pulmonary macrophages with a profibrotic transcriptional program. In vitro, recombinant SLAMF7 was sufficient to induce M2-like macrophage polarization accompanied by CREB/C/EBPβ activation, whereas TANIIA attenuated this response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;SLAMF7 is a potential biomarker and mechanistically relevant mediator linking inflammation and fibrosis in RA-ILD. TANIIA exerts dual protective effects on joi","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158583"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579889","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":"Magnolol as a promising multitarget agent for Alzheimer's disease: Evidence from a systematic evidence synthesis, network pharmacology, and molecular dynamics simulations.","authors":"Yiying Qin, Xiaoyu Dong, Chong Zhang, Jianfei Nao","doi":"10.1016/j.phymed.2026.158586","DOIUrl":"10.1016/j.phymed.2026.158586","url":null,"abstract":"<p><strong>Objective: </strong>This study provides systematic synthesis of therapeutic effects of magnolol (MN) in preclinical Alzheimer's disease (AD) models and integrates network pharmacology with molecular dynamics (MD) simulations to predict its core targets and binding stability.</p><p><strong>Methods: </strong>Systematic literature search was conducted in PubMed, CNKI, Wanfang, and Google Scholar up to January 1, 2026 following PRISMA guidelines. Network pharmacology, molecular docking, and 100 ns MD simulations were used to identify common targets, evaluate binding affinities, and assess complex stability.</p><p><strong>Results: </strong>Fourteen studies (seven in vivo, five in vitro, two combined) were included. MN consistently ameliorated cognitive deficits and neuropathology through antioxidant, anti-inflammatory, anti-apoptotic, and anti-acetylcholinesterase activities, while preserving mitochondrial and synaptic function. Network pharmacology identified 60 common targets; Protein-Protein Interaction (PPI) analysis revealed five hub genes: AKT1, MMP9, MMP2, ERBB2, and EGFR. Molecular docking showed binding energies below -4.0 kcal/mol for all five targets, and MD simulations confirmed stable binding, with the ERBB2-MN complex exhibiting the lowest root mean square deviation (RMSD) (1.2 Å) and favorable free energy landscape. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations further confirmed that magnolol exhibited binding affinities comparable to the reference co‑crystal ligands. Unlike prior reviews, this study uniquely combines systematic evidence synthesis with computational predictions, identifying ERBB2 as a novel stable target of MN.</p><p><strong>Conclusion: </strong>MN exerts anti-AD effects via multi-pathway and multi-target regulation, with computational predictions aligning with experimental evidence, supporting MN as promising lead compound for AD drug development.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"159 ","pages":"158586"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584615","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":"Effect of Yiqi Fumai lyophilized injection on B-type natriuretic peptide levels in patients with acute decompensated ischemic heart failure: a multicenter, open-label, blinded-outcome, randomized controlled trial.","authors":"Xianliang Wang, Zhiqiang Zhao, Jingyuan Mao, Yue Deng, Zhongyong Liu, Xiaolong Wang, Yingqiang Zhao, Xiaohua Dai, Yonggang Wang, Ruyu Yuan, Chengliang Zhong, Huimin Fan, Ping Xie, Tinghai Du, Hong Zhang, Xiaofeng Wang, Yong Xu, Tianfu Niu, Qiwei Tang, Guanyu Wang, Shuzhong Shang, Xingsheng Zhao, Xulong Yan, Pu Xia, Chaofeng Liu, Bing Deng, Liyue Wang, Huanlin Wu, Bo Dong, Hong Yu, Meisheng Zheng, Zhentao Wang, Guoliang Zhao, Xin Li, Aliman Mahemuti, Zhiming Li, Hongxu Liu, Junqiang Yang, Mingjun Zhao, Ruihong Fan, E Tang, Guoyuan Zhao, Shuai Wang, Zhou Zhou, Jian Zhang, Boli Zhang","doi":"10.1016/j.phymed.2026.158191","DOIUrl":"10.1016/j.phymed.2026.158191","url":null,"abstract":"<p><strong>Background: </strong>Patients with acute decompensated ischemic heart failure (ADIHF) often present with severe clinical symptoms and poor quality of life. In China, Yiqi Fumai lyophilized injection (YQFM) is widely used in the treatment of ADIHF. However, high-quality evidence is still needed to support its efficacy and safety.</p><p><strong>Purpose: </strong>This study aims to assess the therapeutic efficacy and safety of YQFM in patients with ADIHF.</p><p><strong>Study design and methods: </strong>By conducting a multicenter, open-label, blinded-outcome, randomized controlled trial, we recruited patients with ADIHF from 37 hospitals in 20 regions of China from October 2015 to October 2018. Patients were allocated in a 1:1 ratio to either the YQFM group or the control group. Both groups received guideline-directed medical therapy (GDMT), with the YQFM group additionally receiving YQFM for 7 days. The primary outcome included the proportion of patients with a decrease from baseline B-type natriuretic peptide (BNP) value ≥ 30% on day 8 post-randomization. We evaluated the left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, and composite endpoints.</p><p><strong>Results: </strong>A total of 666 patients with ADIHF (332 in the YQFM group and 334 in the control group) were enrolled. The full analysis set (FAS) analysis revealed that the proportion of patients in the YQFM group with a reduction of at least 30% in BNP value on day 8 was higher than that in the control group (175 [55.21%] vs. 135 [41.93%], one-sided p < 0.001, two-sided p < 0.001; RR, 1.32 [95% CI, 1.12-1.56]). The YQFM group showed statistically significant improvements in LVEF, NYHA functional class, and MLHFQ scores compared to controls. There was no statistically significant difference between the two groups regarding composite endpoint events and adverse events during the follow-up period.</p><p><strong>Conclusions: </strong>Based on GDMT, the combined use of YQFM was associated with further reductions in BNP levels, improve quality of life and cardiac function in patients with ADIHF, without increasing safety risks. However, no significant differences were observed in clinical events, such as mortality or hospitalization, during the follow-up period.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158191"},"PeriodicalIF":11.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779037","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":"Evaluating natural bioactive chronobiotics in a C. elegans circadian disruption system induced by light-temperature entrainment.","authors":"Yiwen Guo, Tao Zhang, Ying Xu, Ming Chang, Ruijie Liu","doi":"10.1016/j.phymed.2026.158129","DOIUrl":"10.1016/j.phymed.2026.158129","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of circadian rhythm disruption (CRD) is increasing due to the worsening light pollution, rising societal stress, and globalized lifestyles. Long-term CRD can cause significant physiological changes and raise the risk of various health disorders. Natural bioactive compounds (NBC) are showing promise as novel circadian modulators because they can precisely target core clock networks, be administered flexibly, and have multi-target effects, requiring efficient screening models.</p><p><strong>Purpose: </strong>The objective of this study was to establish and characterize a CRD model in C. elegans and to explore its applicability for evaluating the chronobiotic potential of NBCs.</p><p><strong>Methods: </strong>A synchronized light-temperature perturbation protocol was used to induce a stable CRD state in C. elegans. The model's validity was rigorously assessed by monitoring locomotor behavioral rhythms and quantifying transcriptional changes in core clock genes. Rhythm integrity and periodicity were analyzed using the Biodare2 platform. The restorative effects of administered nine NBCs were evaluated through this integrated behavioral, physiological, and molecular framework.</p><p><strong>Results: </strong>The environmental perturbation successfully recapitulated key features of human CRD, leading to markedly disturbed behavioral rhythms and altered expression of core clock genes. The model showed good reproducibility and proved suitable for compound evaluation. Several chronobiotic compounds, including nobiletin, serotonin, N-acetylserotonin, melatonin, catechin, and capsaicin, alleviated CRD-associated phenotypes to varying degrees, demonstrating the model's utility for investigating the circadian regulatory effects of NBCs.</p><p><strong>Conclusion: </strong>Our multidimensional analysis in C. elegans reveals that natural bioactive compounds can modulate CRD, offering new perspectives on the therapeutic potential of plant-derived chronobiotics.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158129"},"PeriodicalIF":11.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691771","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}