Phytomedicine最新文献

{"title":"Atraric acid attenuates chronic intermittent hypoxia-induced brain injury via AMPK-mediated Nrf2 and FoxO3a antioxidant pathway activation","authors":"Mengxin Li,&nbsp;Jun Wang,&nbsp;Zihan Xu,&nbsp;Yue Lin,&nbsp;Jingquan Dong","doi":"10.1016/j.phymed.2025.157261","DOIUrl":"10.1016/j.phymed.2025.157261","url":null,"abstract":"<div><h3>Background</h3><div>Obstructive sleep apnea syndrome (OSAS), a chronic disorder affecting approximately 10 % of adults worldwide with heightened prevalence in males and obese populations, induces irreversible neurocognitive impairment. Atraric Acid (AA), a natural depside compound derived from lichens, exhibits dual functional properties through its molecular groups capable of free radical scavenging and metal chelation. However, its therapeutic potential in OSAS-related pathologies remains unexplored.</div></div><div><h3>Objective</h3><div>This study aims to investigate the neuroprotective effects and molecular mechanisms of AA against CIH-induced neuronal damage.</div></div><div><h3>Methods</h3><div>CIH mouse models and hypoxic injury models in HT22 neurons were established. AA was administered to mice at doses of 5, 10, and 20 mg/kg (selected based on literature references and preliminary experiments), and to cells at an optimal concentration of 20 μM (determined by CCK-8 assays). Therapeutic efficacy was evaluated through behavioral tests including the Morris Water Maze, Elevated Plus Maze, and Open Field Test. Neuroprotective effects were assessed via histopathological examination (e.g., neuronal survival in hippocampal CA3 and DG sub-regions) and detection of oxidative stress/ferroptosis markers (e.g., MDA levels, GPX4 expression, and related biomarkers). Transcriptomic sequencing and molecular docking analyses were employed to investigate differentially expressed genes, pathway enrichment, and underlying mechanisms.</div></div><div><h3>Results</h3><div>In vivo and in vitro experiments demonstrated that AA significantly alleviated neuronal damage in CIH mice and enhanced HT22 cell viability. AA down-regulated oxidative stress- and ferroptosis-related gene expression. Transcriptomic sequencing identified AMPK signaling as a key target. Combined AMPK inhibitor (Compound C) and nuclear-cytoplasmic fractionation experiments confirmed that AA synergistically regulates dual antioxidant pathways (Nrf2/HO-1 and FoxO3a/SOD2) via AMPK activation.</div></div><div><h3>Conclusion</h3><div>AA mitigates CIH-induced neurocognitive impairment by AMPK-dependent activation of the Nrf2/HO-1 and FoxO3a/SOD2 axes, establishing a dual antioxidant-ferroptosis defense barrier. This study is the first to systematically elucidate AA's molecular mechanisms using transcriptomics data integrated with computational simulations, providing novel therapeutic targets and a translational paradigm for developing natural compound-based therapies for OSAS.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157261"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102865","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":"Elevated isatin ameliorates heart injury in patients with myocardial infarction after rehabilitation treatment-based metabolomics screening","authors":"Bing Zhao ,&nbsp;Kehan Wu ,&nbsp;Dili Sun ,&nbsp;Jianfu Zhu ,&nbsp;Weijie Liu ,&nbsp;Shuting Yang ,&nbsp;Xin Liao ,&nbsp;Zishan Li ,&nbsp;Xiaolong Lin ,&nbsp;Xiangdong Yang ,&nbsp;Chun Xiao","doi":"10.1016/j.phymed.2025.157260","DOIUrl":"10.1016/j.phymed.2025.157260","url":null,"abstract":"<div><h3>Background</h3><div>Rehabilitation exercise after acute myocardial infarction is helpful for cardiac function recovery. Isatin, an endogenous indole derivative of tryptophan metabolism, exhibits anti-inflammatory and antioxidant properties, but its role in myocardial injury repair post-myocardial infarction (MI) remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate isatin's cardioprotective effects and molecular mechanisms in post-rehabilitation AMI patients through multi-omics approaches.</div></div><div><h3>Study design</h3><div>This study aimed to systematically investigate the protective effects and molecular mechanisms of isatin on cardiac injury in patients with AMI following rehabilitation, using untargeted metabolomics, HuProt™ microarray, network pharmacology (NP), surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD), animal models, and cell experiments.</div></div><div><h3>Methods</h3><div>Serum isatin levels were measured in STEMI patients’ pre-/post-Enhanced external counterpulsation (EECP) rehabilitation using untargeted metabolomics. HuProt^TM microarray and NP was used to identify the downstream targets of isatin, validated through SPR, molecular docking, and dynamics. A murine AMI model was applied to assess the protective function of isatin. H₂O₂-treated cardiomyocytes and LPS-treated macrophages were used to explore the potential protective mechanisms of isatin.</div></div><div><h3>Results</h3><div>EECP elevated serum isatin in STEMI patients, correlating with better cardiopulmonary function. S100A8 was identified as the primary target by HuProt™ microarray and NP. Isatin formed a 2.1 Å hydrogen bond with S100A8-GLU41. SPR KD=57.9 μM; Docking score=−5.37 kcal/mol; MD ΔG=−15.35 ± 1.95 kcal/mol. Isatin improved cardiac function in AMI mice. Isatin enhanced HL-1 cardiomyocyte viability while reducing apoptosis, and decreased macrophage IL-1β, IL-6, IL-1α, and TNF-α secretion.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that EECP enhances cardiac rehabilitation in STEMI patients by upregulating endogenous isatin, which exerts cardioprotective effects through direct targeting of S100A8, leading to improved cardiac function and reduced oxidative stress and inflammation, with the molecular mechanism confirmed by integrated multi-omics analyses.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157260"},"PeriodicalIF":8.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109645","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":"Daurisoline inhibits pancreatic cancer progression by direct binding to PPARα and blocking its ubiquitination-mediated degradation","authors":"Dongchao Xu ,&nbsp;Yuanling Zhu ,&nbsp;Wuhan Ye ,&nbsp;Yuhua Yu ,&nbsp;Xuehui Wang ,&nbsp;Chenshan Xu ,&nbsp;Ke Jiang ,&nbsp;Wangyang Chen ,&nbsp;Xiaofeng Zhang ,&nbsp;Hongzhang Shen","doi":"10.1016/j.phymed.2025.157245","DOIUrl":"10.1016/j.phymed.2025.157245","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic cancer (PC) is well known for its high lethality, and limited therapeutic options are currently available. Daurisoline (DAU), a bisbenzylisoquinoline alkaloid isolated from <em>Menispermum dauricum</em> DC., has demonstrated antitumor effects in several cancers, although its precise mechanism of action remains unclear.</div></div><div><h3>Purpose</h3><div>This study evaluated the DAU-mediated inhibition of pancreatic cancer and the mechanisms responsible.</div></div><div><h3>Methods</h3><div>DAU's inhibitory effects on PC cells were measured through EdU, CCK-8, wound healing, Transwell, and flow cytometry assays. Bioinformatics analysis revealed molecular expression alterations between PC cells treated with or without DAU. The roles of the PPARα and JAK2/STAT3 pathway in DAU-mediated PC suppression were investigated via PPARα lentiviral transduction and STAT3 activator treatment, respectively. Coimmunoprecipitation assays were performed to confirm the impact of DAU on PPARα ubiquitination and identify the specific ubiquitin ligase involved.</div></div><div><h3>Results</h3><div>Our findings revealed that DAU suppresses the proliferation of pancreatic cancer cells in a time- and dose-dependent manner while also inhibiting cell migration and invasion. Additionally, DAU arrests the cell cycle at the G1 phase and induces apoptosis. Mechanistically, bioinformatics analysis combined with experimental validation demonstrated that DAU binds to PPARα, increases its expression, and subsequently suppresses JAK2/STAT3 signaling. Notably, DAU competitively blocks the Trim63–PPARα interaction by binding to PPARα, thereby suppressing PPARα ubiquitination to increase its protein stability.</div></div><div><h3>Conclusion</h3><div>DAU inhibits the JAK2/STAT3 signaling pathway by preventing PPARα ubiquitination, thereby suppressing the progression of PC cells. This research provides a new therapeutic strategy and a promising compound for treatment of PC through suppression of the ubiquitination pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157245"},"PeriodicalIF":8.3,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102872","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 multi-omics reveals that Salvia miltiorrhiza active fraction ameliorates rheumatoid arthritis in rats via inhibiting inflammation and ferroptosis","authors":"Zhaokun Yin,&nbsp;Shiqi Luo,&nbsp;Zhiyan Qin,&nbsp;Jianxun Song,&nbsp;Lei Zhang,&nbsp;Gengyi Zhang,&nbsp;Fangqing Ning,&nbsp;Min Huang,&nbsp;Jing Jin","doi":"10.1016/j.phymed.2025.157258","DOIUrl":"10.1016/j.phymed.2025.157258","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic, highly disabling autoimmune disease requiring lifelong management, yet current therapies carry substantial long-term toxicity and high costs. <em>Salvia miltiorrhiza</em> is used clinically in the treatment of RA due to its pharmacological properties such as promoting blood circulation, removing blood stasis, and anti-inflammatory effects. However, the specific active fraction of <em>Salvia miltiorrhiza</em> responsible for its therapeutic effect on RA and the underlying mechanism remains unclear.</div></div><div><h3>Objective</h3><div>To explore active fraction from <em>Salvia miltiorrhiza</em> for the treatment of RA and elucidate their underlying mechanisms.</div></div><div><h3>Methods</h3><div>The active fraction of <em>Salvia miltiorrhiza</em> was screened via <em>in vitro</em> anti-inflammatory assay and <em>in vivo</em> pharmacokinetic evaluation. The composition was analyzed using UHPLC-Q Exactive-MS/MS and HPLC. An <em>in vivo</em> model of RA was established in rats using the collagen-induced arthritis (CIA) method. Therapeutic effects were assessed by RT-qPCR, Western Blot, and ELISA. Mechanisms were predicted via multi-omics analysis and validated using Western Blot, immunofluorescence, RT-qPCR, and fluorescent probes.</div></div><div><h3>Results</h3><div>One ethyl acetate extract (named ET) was identified as the active fraction from <em>Salvia miltiorrhiza</em>. In RA rats, ET treatment significantly delayed disease progression and alleviated pathological manifestations. Multi-omics analysis revealed ET modulated amino acid pathways, and impacted macrophage metabolic, inflammation and ferroptosis pathways. Western Blot, immunofluorescence, and RT-qPCR showed that ET not only directly inhibited macrophage inflammatory responses but also indirectly suppressed the activation of fibroblast-like synoviocytes by regulating macrophages. At the same time, ET effectively blocks the ferroptosis process by simultaneously regulating lipid peroxidation and antioxidant signaling. Furthermore, ET's five principal compounds, salvianolic acid B (SalB), dihydrotanshinone I (DIH), cryptotanshinone (CTS), tanshinone I (TanI), and tanshinone IIA (TanIIA), demonstrated inhibitory effects on both inflammation and ferroptosis.</div></div><div><h3>Conclusion</h3><div>The <em>Salvia miltiorrhiza</em> active fraction ET ameliorates RA pathology by simultaneously regulating inflammation, ferroptosis, amino acid metabolism and synoviocyte dysregulation, demonstrating significant therapeutic potential for RA treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157258"},"PeriodicalIF":8.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102906","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":"Ferulic acid ameliorates TLR4-mediated macrophage activation by irreversibly binding to peroxiredoxin 1 to inhibit its dimerization and secretion","authors":"Jie Gao ,&nbsp;Jin Yan ,&nbsp;Xingwang Zu ,&nbsp;Yanyan Xu ,&nbsp;Shilong Wang ,&nbsp;Yue Li ,&nbsp;Zhenying Zhao ,&nbsp;Yuanyuan Hou ,&nbsp;Gang Bai","doi":"10.1016/j.phymed.2025.157254","DOIUrl":"10.1016/j.phymed.2025.157254","url":null,"abstract":"<div><h3>Background</h3><div>In the innate immune system, damage-associated molecular patterns (DAMPs) released by damaged cells, such as peroxiredoxin 1 (PRDX1), interact with Toll-like receptor 4 (TLR4), exacerbating inflammation and tissue injury. Ferulic acid (FA), a dietary and herbal phenolic compound, exhibits notable anti-inflammatory properties. However, the precise anti-inflammatory mechanisms of FA are not fully understood.</div></div><div><h3>Purpose</h3><div>The objective of this study was to elucidate mechanisms underlying the anti-inflammatory effects of FA.</div></div><div><h3>Methods</h3><div>Lipopolysaccharide (LPS) was intratracheally instilled to establish a mouse model of LPS-induced pneumonia. Different doses of FA were injected intraperitoneally, and their anti-inflammatory effects were evaluated. An alkynyl-modified FA probe was used in conjunction with various chemobiological strategies to explore the localization, capture, and identification of FA targets. The pharmacophore of FA and its mechanisms of interaction with its target or pathway were further validated using rigorous biochemical assays and comprehensive transcriptomic profiling. The proposed mechanism of FA against systemic inflammation was validated in mice administered LPS intraperitoneally.</div></div><div><h3>Results</h3><div>FA alleviated LPS-induced pulmonary inflammation in mice by selectively targeting macrophages. Subsequently, PRDX1 was identified as an irreversible FA-binding target. Mechanistic investigations revealed that α,β-unsaturated ketone in FA serves as a critical pharmacophore that covalently binds to the Cys173 residue of PRDX1. This covalent binding event effectively suppressed PRDX1 dimerization, resulting in reduced PRDX1 secretion. The co-localization assay demonstrated that FA reduced TLR4-binding PRDX1 in LPS-treated RAW264.7 cells. Transcriptomic analysis indicated that NF-κB and TNF signaling pathways, downstream of TLR4 signaling, were involved in the FA-mediated anti-inflammatory effects. Reduction of TLR4 activation caused by FA treatment decreased levels of downstream inflammatory cytokines in LPS-treated RAW264.7 cells. Finally, reduced co-localization of TLR4 and PRDX1 by FA was confirmed in the lung slices of mice with LPS-induced intratracheal inflammation. FA also reduced PRDX1 dimerization and mitigated inflammation in mice administered LPS intraperitoneally.</div></div><div><h3>Conclusion</h3><div>Our study elucidated a novel mechanism in which FA covalently binds to the Cys173 residue of PRDX1, suppressing its dimerization and secretion and thereby alleviating inflammation by modulating the PRDX1/TLR4 signaling pathway. Our findings redefine plant phenylacrylic acids as covalent modulators of DAMPs, with therapeutic potential for ameliorating inflammation beyond conventional antioxidants.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157254"},"PeriodicalIF":8.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086915","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":"Moracin N alleviates ischaemic brain injury in mice by suppressing neuronal ferroptosis via the activation of the Keap1/Nrf2 signalling pathway","authors":"Jianbin Zhang ,&nbsp;Qian Xia ,&nbsp;Gaofeng Zhan ,&nbsp;Xue Zhang ,&nbsp;Shuai Gao ,&nbsp;Tangrui Han ,&nbsp;Yilin Zhao ,&nbsp;Xing Li ,&nbsp;Yonghong Wang","doi":"10.1016/j.phymed.2025.157253","DOIUrl":"10.1016/j.phymed.2025.157253","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence suggests that oxidative stress-induced lipid peroxidation ultimately results in ferroptosis, which contributes to the progression of ischaemic brain injury. Moracin N is a leading chemical purified from mulberry leaves. Previous studies have reported that moracin N has good antioxidant activity. However, the specific impact of moracin N on ischaemic stroke have not been determined.</div></div><div><h3>Purpose</h3><div>The present research sought to investigate the neuroprotective effects and mechanisms by which moracin N protects against ferroptosis after ischaemic stroke.</div></div><div><h3>Methods</h3><div>An animal model of ischaemic stroke was established via middle cerebral artery occlusion (MCAO) in mice. Mice received moracin N (20 mg·kg⁻¹·d⁻¹) via intracerebroventricular injection for three days before the start of reperfusion.</div></div><div><h3>Results</h3><div>Moracin N treatment reduced the brain infarct volume and water content, attenuated neurological deficit scores, and improved long-term neurological function recovery in a mouse model of ischaemic stroke (<em>p</em> &lt; 0.05). Moreover, moracin N treatment prevented ferroptosis in the brains of MCAO mice and in primary neurons challenged with oxygen-glucose deprivation <em>in vitro</em> by downregulating FTH1 and ACSL4 and increasing glutathione synthesis (<em>p</em> &lt; 0.05). Mechanistic studies revealed that moracin N increased the activation of the Keap1/Nrf2 signalling pathway. Finally, the neuroprotective effects of moracin N were blocked by the use of ML385, an Nrf2 inhibitor, as evidenced by the excessive iron accumulation and deactivation of the ferroptosis defence system (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Moracin N suppresses oxidative stress-induced neuronal cell death after ischaemic stroke by inhibiting ferroptosis via the Keap1/Nrf2 signalling pathway, indicating that it could serve as a potential therapeutic candidate for cerebral ischaemia.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157253"},"PeriodicalIF":8.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092328","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":"Hmong medicine tooth-fixing formula promotes bone repair in periodontitis","authors":"Ming Dong ,&nbsp;Shuo Liu ,&nbsp;Haibo Sun,&nbsp;Meichen Tong,&nbsp;Qianyang Chen,&nbsp;Shuixiang Guo,&nbsp;Gege Zhang,&nbsp;Chun Shi,&nbsp;Lina Wang,&nbsp;Weidong Niu","doi":"10.1016/j.phymed.2025.157255","DOIUrl":"10.1016/j.phymed.2025.157255","url":null,"abstract":"<div><h3>Background</h3><div>Periodontitis is the number one cause of adult tooth loss worldwide. The main treatments for periodontitis are removed tartar, surgery, and medication, but none of them can bring about a cure. Traditional Chinese medicine as an adjunct to modulation of the host immune response in the treatment of periodontitis needs to be further researched and explored.</div></div><div><h3>Objective</h3><div>This study investigated the effect of Hmong Medicine Tooth-fixing Formula (HM-TF) on periosteal bone repair <em>in vivo</em> and <em>in vitro</em> to provide an experimental basis for the use of the Hmong medicine in the clinical treatment of periodontitis.</div></div><div><h3>Methods</h3><div>Screening of HM-TF and periodontitis co-action targets by network pharmacology analysis. The effects of HM-TF on the proliferation and differentiation of osteoblasts and osteoclasts were investigated by CCK-8 assay, Real-time qPCR, western blotting, ALP, alizarin red S, and TRAP staining. A rat periodontitis model was established, and micro-computed tomography (CT) and hematoxylin and eosin (HE) staining experiments were carried out to study the effect of HM-TF on bone repair and investigate its biosafety.</div></div><div><h3>Results</h3><div>The core active ingredients of HM-TF for treating periodontitis include quercetin, luteolin, kaempferol, etc. One of the main targets of HM-TF in periodontitis is RXRα, and all the active ingredients can effectively bind to RXRα. HM-TF enhanced the growth of osteoblasts by increasing the production of RXRα and factors related to bone formation. Additionally, it hindered the development of osteoclasts by reducing the expression of factors related to osteoclasts. Three-dimensional (3D) micro-CT, HE staining and immunohistochemical staining showed that HM-TF ameliorated the alveolar bone destruction caused by periodontitis in rats, and the effect was better than that of metronidazole.</div></div><div><h3>Conclusion</h3><div>One of the main intersecting targets of HM-TF and periodontitis is RXRα. HM-TF promoted bone repair in rats with periodontitis and had good biocompatibility.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157255"},"PeriodicalIF":8.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081411","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":"Comparison of the efficacy and action mechanism of Chinese patent medicines for liver fibrosis and cirrhosis","authors":"Lingping Fu ,&nbsp;Jin Xie ,&nbsp;ZeXin Wang ,&nbsp;Tao Jiang ,&nbsp;Yi Zeng ,&nbsp;Jing Yan ,&nbsp;Rong Sun ,&nbsp;Mengshuang Huang ,&nbsp;Shengyi Du ,&nbsp;Xiaobao Wang ,&nbsp;Yuyang Liu ,&nbsp;Kailai Xi ,&nbsp;Ailin Chen ,&nbsp;Xiao Ma ,&nbsp;Jinhao Zeng ,&nbsp;Thomas Efferth","doi":"10.1016/j.phymed.2025.157246","DOIUrl":"10.1016/j.phymed.2025.157246","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Liver fibrosis is a critical stage in liver disease progression and can advance to cirrhosis without appropriate treatment. Hepatitis B virus infection is the primary cause of liver fibrosis. Antiviral drugs, &lt;em&gt;e.g.&lt;/em&gt;, entecavir, are widely used to treat liver fibrosis and cirrhosis. Additionally, Chinese patent medicines, such as &lt;em&gt;Biejiajian&lt;/em&gt; Pill (BJP), &lt;em&gt;Liuwei Wuling&lt;/em&gt; Tablet (LWT), &lt;em&gt;Fufang Biejia Ruangan&lt;/em&gt; Tablet (FFT), &lt;em&gt;Fuzheng Huayu&lt;/em&gt; Capsule (FZC), and &lt;em&gt;Anluo Huaxian&lt;/em&gt; Pill (AHP), demonstrate therapeutic effects. However, there is still insufficient evidence-based agreement on the most effective therapies and how they work.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study aims to identify the most effective Chinese patent medicines for treating liver fibrosis and cirrhosis by combining network meta-analysis and network pharmacology. It also summarises and evaluates the potential mechanisms of effective treatment methods based on published clinical research data. The aim is to provide scientific evidence for clinical decision-making. Finally, these results were verified through experiments. The aim is to provide a scientific basis for clinical decision-making.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a comprehensive search of eight databases (PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, China National Knowledge Infrastructure (CNKI), Weipu Database (VIP), and Wanfang) for studies published up to April 2025. After applying inclusion and exclusion criteria, clinical outcomes such as Hyaluronic Acid (HA), Laminin (LN), Type IV Collagen (IV-C), Type III Procollagen (PC-III), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Total Bilirubin (TBIL) were analyzed. A protein-protein interaction (PPI) network was constructed using network pharmacology, with core genes identified via CytoHubba in CytoScape 3.10.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to explore the underlying mechanisms. Next, we validated these predictions using &lt;em&gt;in vivo&lt;/em&gt; experiments, observing pathological changes through HE Staining, Masson’s Trichrome Staining, Picro Sirius Red Staining, and Immunohistochemistry, and performing protein expression analysis using Western blotting.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 380 studies involving 37,380 patients, were included. Surface Under the Cumulative Ranking Curve (SUCRA) and Rank 1 probability were used to assess the therapeutic efficacy of each prescription. For liver fibrosis, AHP was the most effective, followed by LWT, FZC, BJP, and FFT. In cirrhosis treatment, LWT was the most effective, followed by AHP, FZC, BJP, and FFT. Combined with network pharmacology analyses revealed that AHP and LWT might play a role in liver fibrosis and cirrhosis by regulating targets such as Signal Transducer and Activator of Transcription 3 (STAT3","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157246"},"PeriodicalIF":8.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108164","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":"Quercetagetin alleviates ischemic stroke injury by preserving macrophage/microglia homeostasis via inhibiting ACP5","authors":"Chang Liu ,&nbsp;Qi Wang ,&nbsp;Enran Liu ,&nbsp;Zhixi Li ,&nbsp;Haijing Sui ,&nbsp;Jiaqi Jin ,&nbsp;Guangmin Chen ,&nbsp;Chenglong Li ,&nbsp;Hongyu Wang ,&nbsp;Zhenyu Sun ,&nbsp;Hongjie Xi","doi":"10.1016/j.phymed.2025.157256","DOIUrl":"10.1016/j.phymed.2025.157256","url":null,"abstract":"<div><h3>Background</h3><div>The proinflammatory response triggered by macrophages/microglia plays a crucial role in the prognosis of acute ischemic stroke (AIS). Identifying novel targets to regulate the homeostasis of these cells is essential. Developing therapeutic strategies based on these targets could significantly improve AIS treatment outcomes.</div></div><div><h3>Purpose</h3><div>This study aims to identify new regulatory targets for macrophages/microglia homeostasis and to develop effective therapeutic strategies for AIS.</div></div><div><h3>Study Design and Methods</h3><div>Macrophage infiltration in AIS patients from GSE58294 and transient middle cerebral artery occlusion (tMCAO) mouse brain was observed using ssGSEA and immunofluorescence (IF). Integrating the MSigDB database, differentially expressed macrophage/microglia-associated genes (DEMAGs) were identified and further screened using machine learning. The protein level of the critical DEMAG in PBMCs, BV2 cells, and mouse brain tissues was detected with ELISA, western blot, IHC, and IF. siRNA was applied to investigate the effect of the critical DEMAG. A natural product library was screened to find a compound that targets the protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis.</div></div><div><h3>Results</h3><div>This experiment observed increased macrophage infiltration in AIS patients. The upregulated critical DEMAG, ACP5, was more frequently detected in AIS patients' PBMCs, oxygen-glucose deprivation and reoxygenation (OGD/R)-treated BV2 cells and tMCAO mouse brain. Targeting the ACP5 protein, quercetagetin (QG) was identified as an inhibitor. QG could ameliorate systemic imbalance, brain injury, and cognitive impairment in tMCAO mice, partly by maintaining macrophage/microglia homeostasis and inhibiting ACP5.</div></div><div><h3>Conclusion</h3><div>This study shows that ACP5 is a new promoter of macrophages/microglia proinflammatory responses, playing a critical role in regulating the excessive inflammation and oxidative stress associated with AIS. Furthermore, QG mitigates AIS-induced brain damage by inhibiting ACP5.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157256"},"PeriodicalIF":8.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092347","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":"Eriocalyxin B induces ferroptosis through SIRT3 inhibition in triple-negative breast cancer","authors":"Xiya Chen ,&nbsp;Jingjing He ,&nbsp;Ge Ge ,&nbsp;Shuangshuang Ma ,&nbsp;Zixuan Chen ,&nbsp;Lan Zhang ,&nbsp;Feng Gao ,&nbsp;Jin Zhang","doi":"10.1016/j.phymed.2025.157257","DOIUrl":"10.1016/j.phymed.2025.157257","url":null,"abstract":"<div><h3>Background</h3><div>Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous breast cancer subtype, remains clinically challenging due to the paucity of actionable therapeutic targets. The unique metabolic landscape of TNBC, characterized by elevated iron and lipid levels, renders it particularly susceptible to ferroptosis, positioning this cell death modality as a promising therapeutic avenue. Eriocalyxin B (Eri B), a natural diterpenoid, exhibits multifaceted anticancer properties that warrant further investigation.</div></div><div><h3>Object</h3><div>To elucidate the therapeutic mechanism of Eri B-induced ferroptosis in TNBC.</div></div><div><h3>Method</h3><div>In this study, the anti-proliferative effects of Eri B on TNBC cells were evaluated using cell colony formation assays, three-dimensional tumor sphere formation assays, EdU incorporation assays, and analysis of the proliferation marker Ki-67. The anti-metastatic potential of Eri B was assessed through wound healing assays, transwell migration assays, immunofluorescence staining, and western blot analysis. Furthermore, RNA sequencing (RNA-seq), flow cytometry, transmission electron microscopy, and western blotting demonstrated that Eri B induces ferroptosis in TNBC cells. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) provided evidence of a direct interaction between Eri B and signal transducer and activator of transcription 3 (STAT3). Moreover, the efficacy and underlying mechanism of Eri B were further validated through SIRT3 overexpression experiments and by employing a STAT3 activator, colivelin. In <em>vivo</em> anti-TNBC activity was confirmed using a xenografted tumor model combined with bioluminescence imaging.</div></div><div><h3>Result</h3><div>For the first time, we demonstrate that Eri B exhibits significant antitumor activity both in <em>vitro</em> and in <em>vivo</em> through the induction of ferroptosis. RNA-seq analysis enabled us to identify and confirm that Eri B induces ferroptosis and oxidative stress by inhibiting sirtuin 3 (SIRT3), which subsequently modulates the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) signaling pathway. Moreover, our findings reveal that Eri B suppresses <em>SIRT3</em> transcription by directly targeting STAT3, thereby regulating the SIRT3-sterol regulatory element-binding transcription factor 1 (SREBP1)-peroxisome proliferator-activated receptor α (PPARα) -mediated fatty acid metabolism and cellular redox homeostasis.</div></div><div><h3>Conclusion</h3><div>In summary, our findings suggest that Eri B functions as a novel inducer of ferroptosis in TNBC, demonstrating potential therapeutic value through the inhibition of SIRT3 in TNBC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157257"},"PeriodicalIF":8.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107694","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}