Phytomedicine最新文献

{"title":"Integrating serum pharmacochemistry, network pharmacology, and metabolomics to explore the protective mechanism of Hua-Feng-Dan in ischemic stroke","authors":"Xiaofeng Yuan ,&nbsp;Xiaoxia He ,&nbsp;Qilin Shu ,&nbsp;Yayang Gao ,&nbsp;Youli Chen ,&nbsp;Jian Xu ,&nbsp;Yongping Zhang ,&nbsp;Guoqiong Cao","doi":"10.1016/j.phymed.2025.157251","DOIUrl":"10.1016/j.phymed.2025.157251","url":null,"abstract":"<div><h3>Background</h3><div>The traditional Chinese medicine Hua-Feng-Dan (HFD) has shown efficacy against ischemic stroke, but how it works remains unclear.</div></div><div><h3>Purpose</h3><div>To elucidate the mechanisms of action of HFD against ischemic stroke.</div></div><div><h3>Methods</h3><div>The effects of HFD on ischemic stroke injury were explored in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The components of HFD and in serum was determined after oral administration using ultra-high performance liquid chromatography followed by mass spectrometry. Potential therapeutic targets of the HFD components in serum were identified through the combination of network pharmacology and metabolomic analysis of serum, then validated through molecular docking and surface plasmon resonance(SPR), as well as immunohistochemistry and western blotting of brain tissue.</div></div><div><h3>Results</h3><div>HFD alleviated nerve function injury, damage to cortical and hippocampal neurons, and oxidative stress induced by MCAO/R, while also shrinking cerebral infarctions and dampening inflammatory responses and neuronal apoptosis. The main ingredients of HFD are flavonoids and alkaloids. Network pharmacology based on chemical components in serum, followed by molecular docking and SPR, identified several potential therapeutic targets, including AKT1 and PIK3CA. Western blotting of brain tissue confirmed that HFD activated PI3K/AKT/mTOR signaling. Metabolomic analysis of serum revealed that HFD helped to renormalize stroke-perturbed metabolic pathways involving glycerophospholipids, arachidonic acid, primary bile acids and tryptophan. It also revealed that HFD downregulated <em>ACHE, PTGS2, CYP19A1</em> and <em>ALOX5,</em> which immunohistochemistry of brain tissue confirmed.</div></div><div><h3>Conclusion</h3><div>HFD exerts therapeutic effects in a rat model of ischemic stroke through multiple pathways and targets, including PI3K/AKT/mTOR signaling; metabolic pathways involving arachidonic and amino acids; and the enzymes encoded by <em>ACHE, MAOA, PTGS2, CYP19A1,</em> and <em>ALOX5</em>. These insights may guide further studies into the mechanisms of HFD, which may help optimize its formulation or lead to next-generation treatments based on individual components.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157251"},"PeriodicalIF":8.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081361","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":"Integrative proteomics and metabolomics reveal that Terrestris saponin D ameliorates pulmonary fibrosis by regulating unsaturated fatty acid biosynthesis","authors":"Shu-Ning Zhang ,&nbsp;Jing-jing Guo ,&nbsp;Long-shan Zhao ,&nbsp;Yu-kun Bo ,&nbsp;Dan Yang ,&nbsp;Xue-miao Yang ,&nbsp;Shu-Min Li ,&nbsp;Guo-dong Wu ,&nbsp;Ming An","doi":"10.1016/j.phymed.2025.157232","DOIUrl":"10.1016/j.phymed.2025.157232","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disorder with an unclear pathogenesis and irreversible progression. <em>Terrestris saponin</em> D (TED), a bioactive compound from the traditional medicinal herb Tribulus terrestris, has demonstrated significant inhibitory effects on PF progression. However, its specific molecular targets in PF treatment and underlying regulatory mechanisms at the proteomic and metabolic levels remain to be fully elucidated.</div></div><div><h3>Purpose</h3><div>This study aims to comprehensively analyze the potential pharmacological mechanisms of TED in ameliorating PF by investigating dynamic correlations at both the proteomic and metabolic levels. It also seeks to transcend the limitations of traditional single-target paradigms by identifying novel functions of key proteins involved in TED-mediated PF amelioration and elucidating TED’s regulatory effects on critical metabolic pathways. This research provides an innovative theoretical basis for understanding how individual components of traditional Chinese medicine can intervene in complex diseases, establishing a new direction for developing anti-PF treatment strategies based on metabolic regulation.</div></div><div><h3>Study design/Methods</h3><div>The anti-PF efficacy of TED was evaluated in a murine PF model by assessing lung histopathology and inflammatory/fibrotic markers. Integrative 4D-SmartDIA quantitative proteomics and untargeted metabolomics explored its mechanisms in pulmonary fibrosis progression, with findings validated by correlation analyses and further experiments.</div></div><div><h3>Results</h3><div>TED mitigated PF progression by suppressing inflammatory responses and reducing collagen deposition. Quantitative 4D-SmartDIA proteomics analysis identified stearoyl-CoA desaturase 2 (SCD2) as a potential target of TED in PF. Dynamic metabolic profiling demonstrated that TED administration restores dysregulated endogenous metabolism involving arachidonic acid, carnosine, and proline metabolic pathways during fibrotic progression. These findings implicate SCD2-mediated biosynthesis of unsaturated fatty acids (UFAs) as the primary mechanism underlying TED’s anti-PF effects. Computational docking analyses confirmed stable, spontaneous binding between TED and SCD2. Subsequent Western blotting revealed that TED upregulates SCD2 expression and phosphorylation. Additional studies suggest that TED ameliorates PF by modulating unsaturated fatty acid (UFA) levels, consistent with the omics findings. Co-immunoprecipitation (Co-IP) was used to assess SCD2 phosphorylation.</div></div><div><h3>Conclusion</h3><div>These findings indicate that TED alleviates PF by modulating SCD2 expression and phosphorylation, thereby influencing UFAs biosynthesis. These results highlight potential molecular targets for TED therapy and provide insight into novel regulatory mechanisms of SCD2 in PF.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157232"},"PeriodicalIF":8.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061459","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":"Siweixizangmaoru decoction attenuates collagen-induced arthritis via gut microbiota-dependent SCFA restoration and immunomodulation","authors":"Yunqi Sun ,&nbsp;Xiao Chen ,&nbsp;Tong Wang ,&nbsp;Yanfei Niu ,&nbsp;Mingxue Cui ,&nbsp;Bin Li ,&nbsp;Shan Huang","doi":"10.1016/j.phymed.2025.157249","DOIUrl":"10.1016/j.phymed.2025.157249","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) arises from immune imbalance that may be affected by gut microbiota dysbiosis and dysregulation of their metabolites. Siweixizangmaoru decoction (SXD), a classical formula in Traditional Tibetan Medicine (TTM), alleviates RA symptoms, yet its mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>The aim of this research is to elucidate the mechanism by which the SXD alleviates RA through the gut microbiota-metabolite-immune axis.</div></div><div><h3>Methods</h3><div>A collagen-induced arthritis rat model was established. The effects of SXD on gut microbiota and short-chain fatty acid (SCFA) metabolism were assessed using 16S rRNA sequencing and metabolomics. Flow cytometry performed to quantify the proportions of immune cell in blood and spleen. Moreover, Caco-2 cells was utilized to assess the effects of SXD and butyrate on AMP-activated protein kinase (AMPK) signaling activation.</div></div><div><h3>Results</h3><div>SXD significantly alleviated arthritis symptoms and decreased serum TNF-α and IL-17 levels. SXD reversed the <em>Firmicutes</em>/<em>Bacteroidetes</em> ratio, suppressing the pathogenic genus <em>Desulfovibrio</em> and enriching SCFA-producing <em>Butyricicoccus</em>. SXD significantly upregulated ZO-1, occludin and downregulated zonulin, while enhancing biosynthesis of SCFAs like butyrate. SXD and butyrate enhance tight junction protein expression in Caco-2 cells via AMPK pathway. Correlation analysis revealed strong positive correlations between SCFA levels and tight junction proteins/anti-inflammatory factors, while negative correlations were observed with pro-inflammatory cytokines, intestinal permeability markers and the Th1/Th2 and Th17/Treg ratio.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that SXD alleviates RA by synergistically regulating the gut microbiota-SCFA metabolism-immune homeostasis axis, providing a promising approach for Tibetan medicine targeting the \"gut-joint axis\" in RA therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157249"},"PeriodicalIF":8.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048263","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":"Xiao-Er-An-Shen Granule inhibits dopamine production to ameliorate Tourette syndrome in mice","authors":"Lifang Wei ,&nbsp;Changhui Li ,&nbsp;Daozheng Fang ,&nbsp;Chi Zhang ,&nbsp;Haipiao Huang ,&nbsp;Jinru Wu ,&nbsp;Lin Zheng ,&nbsp;Yinghao Yin ,&nbsp;Qiugu Chen ,&nbsp;Shiying Huang ,&nbsp;Jihang Chen ,&nbsp;Jianping Chen","doi":"10.1016/j.phymed.2025.157243","DOIUrl":"10.1016/j.phymed.2025.157243","url":null,"abstract":"<div><h3>Background</h3><div>Tourette syndrome (TS) is a neuropsychiatric disorder that typically manifests in childhood. Currently, anti-psychotic drugs that aim to reduce dopaminergic hyperinnervation in the brain are recommended for TS. These drugs have been proven to increase the risk of extrapyramidal symptoms, which hinder their use. Gut microbiota has been shown to modulate dopamine (Da) metabolism along gut-brain axis and be relevant to the development of TS, and which may be a novel strategy for TS therapy. Xiao-Er-An-Shen Granule (XEASG) is a clinically prescribed herbal mixture that has demonstrated clinical efficacy in treating TS. The detailed mechanism of XEASG in alleviating TS symptoms through the gut-brain axis however remains incompletely understood.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the effect of XEASG on TS through regulating Da synthesis both in the brain and gut microbiota.</div></div><div><h3>Methods</h3><div>XEASG at doses of 2 and 4 g/kg/d was administered orally to 3,3′-iminodipropionitrile (IDPN)-induced TS model mice. Behavioral assessments, targeted metabolomics analysis, 16S rRNA sequencing and enzyme-linkedimmunosorbent assay (ELISA) were employed to elucidate the therapeutic effects and mechanisms of XEASG for TS treatment.</div></div><div><h3>Results</h3><div>Data showed that XEASG treatment significantly alleviated IDPN-induced tic-like behavior in mice. XEASG significantly reduced Da level in the brain tissues of TS mice, resulting from down-regulated Da synthesis but up-regulated Da degradation. Aberrant Da metabolism was also found in serum and colon contents of TS mice, which was restored by XEASG treatment. Furthermore,16S rRNA sequence revealed that XEASG altered the microbial community composition. Finally, experimental validation confirmed that XEASG suppressed Da synthesis pathway by reducing tyrosine hydroxylase level in the gut microbiota.</div></div><div><h3>Conclusion</h3><div>Our findings reveal that XEASG alleviates TS via inhibiting Da synthesis in the brain and gut, which suggests that the regulation of Da through gut microbiota by XEASG could be a therapeutic strategy for TS treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157243"},"PeriodicalIF":8.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048265","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":"Clinical outcomes and safety of Chinese herbal medicine in the treatment of hyperuricemia: A retrospective real-world study","authors":"Zilin Long ,&nbsp;Houyu Zhao ,&nbsp;Yueqi Yin ,&nbsp;Yexiang Sun ,&nbsp;Peng Shen ,&nbsp;Hongbo Lin ,&nbsp;Junchang Liu ,&nbsp;Siyan Zhan ,&nbsp;Zhiqin Jiang ,&nbsp;Feng Sun","doi":"10.1016/j.phymed.2025.157231","DOIUrl":"10.1016/j.phymed.2025.157231","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia (HUA) has become a bothersome health problem that cannot be ignored. An increasing number of patients with HUA seek Chinese herbal medicine (CHM) as an alternative or complementary treatment. However, there was a lack of real-world evidence on the long-term impact of CHM in HUA populations.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the clinical outcomes and safety of CHM among individuals with HUA in mainland China.</div></div><div><h3>Study design</h3><div>A population-based, active-comparator new-user designed cohort study of patients with HUA was performed using the Yinzhou Regional Health Care Database (YRHCD).</div></div><div><h3>Methods</h3><div>A cox model with propensity score matching was applied to estimate the hazard ratio (HR) of the association between the use of CHM and gouty arthritis (GA). Various subgroup analyses and multiple sensitivity analyses were also performed to demonstrate the robustness of results. The secondary outcomes were drug-induced liver injury (DILI) risk and gouty nephropathy (GN) risk.</div></div><div><h3>Results</h3><div>A total of 40 653 patients with HUA were included from the YRHCD between 2015 and 2024, among whom 35 511 participants were CHM users and 5 142 were benzbromarone (BBR) users. In the primary analysis, the incidence of GA was 34.43 per 1 000 person-years for CHM users and 58.00 per 1 000 person-years for BRR users, respectively. CHM users appeared to have a 43 % reduction in risk of developing GA compared with BBR users with an HR of 0.57 [95 %CI 0.50, 0.65]. In addition, there was comparable safety in DILI between CHM users and BBR users (HR 1.18 [95 % CI 0.93, 1.49]). The results were generally consistent in various subgroup analyses and sensitivity analyses.</div></div><div><h3>Conclusion</h3><div>CHM users improved clinical outcomes in patients with HUA and was safe, which can be a promising complementary therapy for HUA patients.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157231"},"PeriodicalIF":8.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102911","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":"Neuro-skeletal crosstalk: Brain-derived 5-HT mediates the bone-protective effects of β-Sitosterol against postmenopausal osteoporosis","authors":"Kaixuan Wang ,&nbsp;Lining Wang ,&nbsp;Shijie Zhou ,&nbsp;Xi Chen ,&nbsp;Lihui Qian ,&nbsp;Tianchi Zhang ,&nbsp;Xiaoxian Sun ,&nbsp;Muzhe Li ,&nbsp;Mengmin Liu ,&nbsp;Yang Guo ,&nbsp;Yue Hu ,&nbsp;Yong Ma","doi":"10.1016/j.phymed.2025.157248","DOIUrl":"10.1016/j.phymed.2025.157248","url":null,"abstract":"<div><h3>Background</h3><div>Postmenopausal osteoporosis (PMOP) is frequently accompanied by depression, and the underlying neuro-skeletal crosstalk remains unclear. Serotonin and sympathetic nervous system (SNS) activity are implicated in both mood and bone regulation.</div></div><div><h3>Objective</h3><div>To investigate whether β-sitosterol (βS) alleviates PMOP-associated depression and bone loss through modulation of central 5-hydroxytryptamine (5-HT) synthesis and SNS activity.</div></div><div><h3>Design</h3><div>An integration of in vivo and in vitro studies using mouse models and cellular assays.</div></div><div><h3>Methods</h3><div>Ovariectomized (OVX) and 5-HT-deficient mice were treated with βS. Behavioral assessments, micro-CT, immunohistochemistry, enzyme-linked immunosorbent assays (ELISA), Western blotting (WB), and molecular docking were employed to evaluate antidepressant effects, bone parameters, and related signaling pathways. In vitro, βS effects on 5-HT production and osteogenesis were assessed in PC12 cells and BMSCs.</div></div><div><h3>Results</h3><div>βS enhanced brain 5-HT synthesis by activating the SIRT1/NRF2/TPH2 pathway and suppressing MAO-A. It alleviated depressive-like behaviors, reduced SNS activity, and prevented bone loss in both OVX and 5-HT-deficient mice. In vitro, βS increased 5-HT secretion in PC12 cells and promoted osteogenic differentiation in BMSCs via conditioned media.</div></div><div><h3>Conclusion</h3><div>βS restores neuro-skeletal homeostasis by boosting 5-HT-mediated suppression of SNS activity, thereby improving mood and bone health. These findings identify βS as a promising candidate for treating comorbid PMOP and depression. Our study provides the first evidence linking phytosterol therapy to neuro-skeletal regulation in bone loss.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157248"},"PeriodicalIF":8.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081442","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":"Qiangxin bushen decoction attenuates cardiorenal syndrome type II via AMPK/FOXO1-mediated ferroptosis pathway: A multi-omics and experimental study","authors":"Shuo Han ,&nbsp;Hui Zhang ,&nbsp;Junfeng Qian ,&nbsp;Sijie Yao ,&nbsp;Yali Sun ,&nbsp;Xuan Zhao ,&nbsp;Xinyue Ding ,&nbsp;Lina Xing ,&nbsp;Zongjun Liu","doi":"10.1016/j.phymed.2025.157247","DOIUrl":"10.1016/j.phymed.2025.157247","url":null,"abstract":"<div><h3>Background</h3><div>Our previous studies have demonstrated that Qiangxin Bushen Decoction (QBD) exhibits therapeutic effects in heart failure patients complicated with renal insufficiency. However, the precise molecular pathways and pathophysiological mechanisms through which QBD ameliorates cardiorenal syndrome type II (CRS2) progression remain unclear.</div></div><div><h3>Purpose</h3><div>To explore the mechanism of QBD for the treatment of CRS2.</div></div><div><h3>Methods</h3><div>UPLC-Q-TOF-MS was employed to explore comprehensive metabolite profiling from QBD samples. Network pharmacology, RNA-seq, and metabolomics were utilized to predict the bioactive constituents, potential therapeutic targets, and intervention pathways through which QBD exerts its effects on CRS2. Cardiac and renal function in mice were assessed by echocardiography along with serum and urinary biochemical markers. Cardiac and renal tissue samples were collected for histological, protein, and genetic examinations, and targeted genes werevalidated using immunohistochemistry (IHC) staining, western blotting(WB) analysis, and qPCR analysis.</div></div><div><h3>Results</h3><div>A total of 74 compounds were identified in QBD samples, and 118 compounds were detected in QBD-containing serum. Echocardiography revealed significant ventricular remodeling in CRS2 mice, which was markedly ameliorated following QBD treatment. Serum and urine biochemical assays further confirmed that QBD effectively alleviated cardiorenal injury. Histopathological examination demonstrated significantly reduced pathological damage in the heart and kidney tissues of QBD-treated mice. Multimodal validation, including IHC staining, WB, and qPCR analyses, indicated that QBD attenuated tissue ferroptosis by modulating the AMP-activated protein kinase (AMPK)/Forkhead box protein O1 (FOXO1) pathway in CRS2 mice. In vitro experiments using AMPK inhibitor Dorsomorphin and ferroptosis activator Erastin confirmed that QBD exerted its therapeutic effects via this pathway. Integrated transcriptomic and metabolomic analyses revealed that QBD treatment modulated metabolic pathways associated with energy metabolism, oxidative stress, and biosynthetic functions.</div></div><div><h3>Conclusion</h3><div>This study reveals that QBQ exerts its cardiorenal protection for CRS2 through AMPK/FOXO1-dependent ferroptosis inhibition with contemporary multi-omics research tools.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"147 ","pages":"Article 157247"},"PeriodicalIF":8.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081407","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":"5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone-nanoparticle regulation mechanism of basic transcription factor 3 through hypoxia inducible factor-1α ubiquitination mediation to inhibit human hepatoma cell proliferation","authors":"Jiaxin Chen,&nbsp;Yixuan Wang,&nbsp;Shuhan Wang,&nbsp;Haoyi Cheng,&nbsp;Dandan Wang,&nbsp;Jinghao Fu,&nbsp;Jinge Hao,&nbsp;Jing Zhang,&nbsp;Xuewu Zhang","doi":"10.1016/j.phymed.2025.157236","DOIUrl":"10.1016/j.phymed.2025.157236","url":null,"abstract":"<div><h3>Background</h3><div>The main bioactive component of <em>Sorbaria sorbifolia</em>, 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone (TTF1), exhibits anti-cancer activity in human hepatoma cells. To improve its solubility, it can be prepared as nanoparticles (TTF1-NP), however, their role modulating BTF3/HIF-1α ubiquitination and its downstream glycolytic disruption remains unexplored.</div></div><div><h3>Purpose</h3><div>To explore the mechanism by which TTF1-NP inhibits the glycolysis and proliferation of hepatoma cells through BTF3-mediated HIF-1α ubiquitination.</div></div><div><h3>Study design and methods</h3><div>This study investigated TTF1-NP's anti-liver cancer mechanism in <em>vitro</em> and <em>vivo</em>. Under hypoxia, TTF1-NP suppressed hepatoma cell proliferation and glycolysis via CCK-8, cloning, flow cytometry, and western blot. Proteomics and survival analysis linked BTF3 to liver cancer progression. TTF1-NP downregulated BTF3, promoting HIF-1α ubiquitination to inhibit glycolysis, confirmed by overexpression/knockdown experiments. In mouse xenograft and rat primary liver cancer models, TTF1-NP attenuated tumor growth, reduced glycolysis, and enhanced HIF-1α degradation, demonstrating its therapeutic potential.</div></div><div><h3>Results</h3><div>Under hypoxic, TTF1-NP inhibited hepatoma cell proliferation by inducing G0/G1 arrest. TTF1-NP treatment reduced lactate production, ATP, and glucose uptake, and significantly downregulated glycolytic enzymes. It suppressed BTF3 (overexpressed in liver cancer), promoting HIF-1α ubiquitination to block glycolysis and tumor growth. In vivo, TTF1-NP attenuated tumor progression, downregulated BTF3/HIF-1α, enhanced HIF-1α degradation, reduced hepatic radioconcentration and inflammation. Mechanistically, it disrupted BTF3-HIF-1α interaction, promoting HIF-1α ubiquitination and inhibiting glycolytic for antitumor effects.</div></div><div><h3>Conclusion</h3><div>TTF1-NP inhibites BTF3, promoting HIF-1α ubiquitination to suppress glycolysis and hepatoma growth, these results offer a novel dual-targeted anti-tumor strategy and lay a solid foundation for the development of S. sorbifolia and TTF1-NP as innovative anti-tumor candidate drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"147 ","pages":"Article 157236"},"PeriodicalIF":8.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055169","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 three-year review (2023–2025) on the effectiveness of natural products from plants in treating major types of fibrosis","authors":"Jason B.T. Kuete ,&nbsp;Jenifer R.N. Kuete ,&nbsp;Armelle T. Mbaveng ,&nbsp;Victor Kuete ,&nbsp;Thomas Efferth ,&nbsp;Ralf Weiskirchen","doi":"10.1016/j.phymed.2025.157242","DOIUrl":"10.1016/j.phymed.2025.157242","url":null,"abstract":"<div><h3>Background</h3><div>Fibrosis, or fibrotic scarring, is the body’s response to injury that leads to the formation of fibrous connective tissue. It impacts various illnesses and can contribute to mortality. Currently, there are no effective treatments targeting the release of extracellular matrix (ECM) from fibroblasts, highlighting the urgent need for new therapies. Medicinal plants and their derivatives may offer a promising alternative for treating fibrosis.</div></div><div><h3>Purpose</h3><div>This review aims to summarize the findings from reports published between 2023 and 2025 on the role of natural substances derived from plants in the treatment of four major types of fibrosis: myocardial fibrosis (MF), liver fibrosis (LF), pulmonary fibrosis (PF), and renal fibrosis (RF).</div></div><div><h3>Methods</h3><div>Data were sourced from PubMed, Google Scholar, ScienceDirect, and Scopus using terms related to fibrosis, such as \"diagnosis,\" \"treatment,\" \"plant extracts,\" and \"phytochemicals.\" Information on antifibrotic plant extracts and formulations from 2023 to 2025 was compiled.</div></div><div><h3>Results</h3><div>This review presents essential information on four main types of fibrosis and documents 72 botanicals. These consist of 28 individual plants studied separately and 44 combined herbal formulations. The botanicals are categorized according to the different types of fibrosis: 21 for LF, 8 for MF, 23 for PF, and 20 for RF. The review provides detailed information on 10 polyherbal formulations, which include: <em>Guizhi Fuling Wan</em> (GFW), <em>Jiawei Taohe Chengqi</em> decoction (JTCD), <em>Longdan Xiegan Tang</em> (LXT), and <em>Tao-Hong-Si-Wu-Tang</em> (THSWT) for LF; <em>Linggui Zhugan</em> decoction (LGZGD) and <em>Qili Qiangxin</em> (QLQX) for MF; <em>Sha-Shen Mai-Dong</em> (SMT) and <em>Xuanfei Baidu</em> decoction (XFBD) for PF; and <em>Huangqi-Danshen</em> (HDD) and <em>Jian-Pi-Yi-Shen</em> (JPYS) for RF. Additionally, the document lists 35 phytochemicals, which include 19 terpenoids and 16 phenolic compounds.</div></div><div><h3>Conclusion</h3><div>This work highlights that, over the past three years, numerous scientific publications have underscored the importance of medicinal plants in treating various types of fibrosis globally. To improve the management of fibrosis, it is essential to conduct both preclinical and clinical studies on these promising samples to identify potential drug candidates.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157242"},"PeriodicalIF":8.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150522","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":"Modified Xiaoyaosan rescues depression-like behavior via remodeling gut microbiota and leucine metabolism","authors":"Yunhao Zhao ,&nbsp;Qi Wang ,&nbsp;Zhenning Wu ,&nbsp;Yuzhi Zhou ,&nbsp;Xiaoxia Gao ,&nbsp;Wenxia Gong ,&nbsp;Xuemei Qin ,&nbsp;Yan Ren ,&nbsp;Junsheng Tian","doi":"10.1016/j.phymed.2025.157241","DOIUrl":"10.1016/j.phymed.2025.157241","url":null,"abstract":"<div><h3>Background</h3><div>Social avoidance is a hallmark symptom of depression. Although Modified Xiaoyaosan (MXYS) has been reported to attenuate this behavior, the underlying mechanisms remain poorly understood.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the mechanisms by which MXYS alleviates social avoidance, with particular emphasis on gut microbiota composition and leucine metabolism.</div></div><div><h3>Methods</h3><div>A chronic social defeat stress (CSDS) mouse model was established to evaluate the antidepressant effects of MXYS. Fecal samples were subjected to LC–MS-based untargeted metabolomics and 16S rRNA sequencing to characterize alterations in gut microbiota and metabolites. Fecal microbiota transplantation (FMT) was conducted to verify the contribution of gut microbes to MXYS’s antidepressant effects. Furthermore, targeted GC–MS, LC–MS/MS, and Western blotting analyses were employed to elucidate the mechanisms underlying leucine reduction. Finally, exogenous leucine supplementation was administered to determine its potential antidepressant efficacy.</div></div><div><h3>Results</h3><div>MXYS treatment significantly ameliorated CSDS-induced social avoidance and other depression-like behaviors. Integrated metabolomic and 16S rRNA analyses identified leucine metabolism as a potential therapeutic target. MXYS modulated gut microbial composition and functional pathways, particularly those involved in leucine metabolism. FMT experiments confirmed the essential role of gut microbiota in mediating the antidepressant effects of MXYS. Targeted metabolic profiling and protein expression analyses revealed that enhanced microbial degradation of leucine contributed to its systemic reduction. Moreover, leucine supplementation robustly reversed depressive-like behaviors and attenuated hippocampal oxidative stress.</div></div><div><h3>Conclusion</h3><div>MXYS alleviates social avoidance in CSDS mice by modulating gut microbiota–mediated leucine degradation, thereby restoring systemic leucine levels and improving hippocampal oxidative stress.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"147 ","pages":"Article 157241"},"PeriodicalIF":8.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057362","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}