Phytomedicine最新文献

{"title":"Decoding the anti-heart failure effects of Xinbao Pills: AMPKα1 activation and active compound screening","authors":"Zunjiang Li ,&nbsp;Yingxin Long ,&nbsp;Xing Sun ,&nbsp;Aoyin Liu ,&nbsp;Zhenzhu Ding ,&nbsp;Dongli Li ,&nbsp;Yueyao Wang ,&nbsp;Ruifeng Zeng ,&nbsp;Quanle Liu ,&nbsp;Baijian Chen ,&nbsp;Hong Nie ,&nbsp;Wei Zhu ,&nbsp;Banghan Ding","doi":"10.1016/j.phymed.2025.157016","DOIUrl":"10.1016/j.phymed.2025.157016","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have focused on the protective effect of Xinbao pills (XBP) on heart failure (HF) irrespective of the ejection fraction-based classification, However, there are still no reports on the mechanism and active compounds of XBP in HF with reduced ejection fraction (HFrEF).</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the anti-HFrEF effects and mechanism of XBP and identify its active compounds.</div></div><div><h3>Methods</h3><div>Doxorubicin-induced HFrEF rats and H₂O₂-induced damage to H9c2 cardiomyocytes were established. Transthoracic echocardiography, HE staining, commercial assay kits, and cellular flow cytometry analysis were used to evaluate the cardioprotective effect of XBP. Subsequently, myocardial energy metabolomics and transcriptomics were used to explore the mechanism of XBP, which was verified via western blotting and commercial assay kits. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-throughput molecular docking, molecular dynamics simulation analysis and <em>in vitro</em> verification were applied to explore the active ingredients of XBP.</div></div><div><h3>Results</h3><div>XBP improved cardiac function (ejection fraction: 81.1 vs DOX 55.3 %, <em>p</em> &lt; 0.001, and cardiac output: 71.3 vs DOX 47.3 μl/min, <em>p</em> = 0.002 etc.) in HFrEF rats, and protected against myocardial H9c2 cardiomyocyte damage (cell viability: 0.56 vs DOX 0.35, <em>p</em> &lt; 0.05, and LDH: 3562 vs DOX 7073 ng/ml, <em>p</em> &lt; 0.05 etc.), enhanced myocardial energy metabolism levels(ATP: 2887 vs DOX 809.9 nM, <em>p</em> &lt; 0.05, and Glutamine: 387.4 vs DOX 212.8 μM, <em>p</em> &lt; 0.0001 etc.), and protected mitochondrial respiratory function (maximum respiratory capacity: 219.7 vs DOX 81.4 pmol/min, <em>p</em> &lt; 0.05, and glycolytic function: 11.17 vs DOX 5.62 pmol/min, <em>p</em> &lt; 0.001 etc.), which required the activation of AMPKα1. Inhibition of AMPKα1 blocked the cardioprotective effect of XBP. In contrast, activation of the AMPKα1 pathway can exert a similar protective effect as that of XBP. Additionally, Kaempferol-7-O-glucoside, Luteolin-7-O-glucoside, Grossamide, Isorhamnetin-3,7-O-diglucoside, and Kaempferol-7-O-rhamnoside were identified as key compounds that activating AMPKα1 and protecting against myocardial injury.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that the AMPKα1 pathway is integral to the XBP’s anti-HF effects, with key identified compounds likely contributing to the XBP’s pharmacological protection, providing a novel mechanistic understanding and identifying the main active compounds of XBP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157016"},"PeriodicalIF":6.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534732","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":"Gan-Mai-Da-Zao decoction ameliorates depressive-like behaviors in CUMS mice via the microbiota-metabolism-inflammation axis","authors":"Biqun Zhang ,&nbsp;Jiaqi Ji ,&nbsp;Xuesong Zhang ,&nbsp;Xiaoqin Yu ,&nbsp;Xiaosong Hu ,&nbsp;Jiayao Liu ,&nbsp;Ping Wang ,&nbsp;Zhou Lan","doi":"10.1016/j.phymed.2025.157018","DOIUrl":"10.1016/j.phymed.2025.157018","url":null,"abstract":"<div><h3>Background</h3><div>Gan-Mai-Da-Zao decoction (GMDZ), a traditional Chinese formulation used as both food and medicines, exhibits antidepressant effects. However, its underlying mechanisms, particularly those involving the gut-brain axis, remain unclear.</div></div><div><h3>Purpose</h3><div>To integrate gut microbiota profiling, metabolomics, and neuroinflammation to systematically elucidate GMDZ's antidepressant mechanisms.</div></div><div><h3>Study design and Methods</h3><div>Mice with depression-like behaviors were induced using a chronic unpredictable mild stress (CUMS) approach. Behavioral tests, multi-omics approaches (metabolomics, 16 s rRNA sequencing), and molecular biology techniques (histopathology, immunofluorescence, ELISA, qPCR, Western blot) were employed to investigate GMDZ’s multi-target mechanisms.</div></div><div><h3>Results</h3><div>We identified 108 bioactive components, with 58 detected in plasma and 43 in the cerebral cortex, confirming systemic exposure and cerebral penetration of key constituents. GMDZ significantly ameliorated depressive-like behaviors and attenuated associated neuronal and colonic pathological damage. Mechanistically, GMDZ exerted its antidepressant effects through three novel and interconnected pathways: (1) Modulating gut microbiota composition and altering fecal and plasma metabolite profiles; (2) Reducing peripheral and central pro-inflammatory cytokines levels and suppressing NLRP3 inflammasome pathway activation; and (3) Enhancing blood-brain barrier (BBB) integrity by up-regulating occludin and claudin-5.</div></div><div><h3>Conclusion</h3><div>GMDZ exerts antidepressant effects via a novel multi-target regulatory mechanism involving the microbiota-metabolite-inflammation axis. This study significantly advances our understanding of GMDZ’s gut-brain axis mechanism and offers a new paradigm for mechanistic investigations of traditional Chinese medicine.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157018"},"PeriodicalIF":6.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501951","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":"Naringenin exerts antiarrhythmic action in septic cardiomyopathy by downregulating the CaMKⅡ/Drp1/Bcl-2 pathway","authors":"Yali Zhang ,&nbsp;Yu Zhang ,&nbsp;Hongmei Deng ,&nbsp;Qishu Zeng ,&nbsp;Zhu Zhu ,&nbsp;Zhaolun Zhang ,&nbsp;Chunyu Zhang ,&nbsp;Minghao Li ,&nbsp;Jianhong Li ,&nbsp;Guang Li ,&nbsp;Jian Feng","doi":"10.1016/j.phymed.2025.157006","DOIUrl":"10.1016/j.phymed.2025.157006","url":null,"abstract":"<div><h3>Background</h3><div>Septic cardiomyopathy (SCM) is associated with sepsis and is often accompanied by progressive arrhythmia. Naringenin (Nar) is a natural dihydroflavonoid compound that plays a protective role in various cardiovascular diseases. Calcium/calmodulin-dependent kinase II (CaMKII) is a key therapeutic target in cardiac arrhythmias.</div></div><div><h3>Purpose</h3><div>This study investigated the effect of naringenin on arrhythmia and cardiac electrophysiology in SCM and explored the mechanism involved.</div></div><div><h3>Methods</h3><div>Lipopolysaccharide was used to establish SCM in a mouse model and in an H9c2 cell line. The protective role of naringenin in SCM was investigated by pretreatment with naringenin, amiodarone, and a CaMKII inhibitor (KN-93). Cardiac function, susceptibility to arrhythmia, and electrophysiological changes were assessed in the mice using echocardiography, electrocardiography, and optical mapping techniques. Network pharmacology approaches, molecular docking, and molecular dynamics simulations were used to screen for pivotal targets. The mechanism(s) underlying the protective impact of naringenin on SCM were examined in vivo, ex vivo, and in vitro.</div></div><div><h3>Results</h3><div>Naringenin protected against SCM by exerting anti-inflammatory effects, alleviating myocardial injury, improving cardiac dysfunction, reducing the susceptibility to arrhythmia, and stabilizing electrophysiology. Network pharmacology, molecular docking, and molecular dynamics simulations indicated that the key target protein of naringenin may be Bcl-2. Further studies confirmed that naringenin attenuated apoptosis, improved mitochondrial dysfunction, and downregulated the CaMKⅡ/Drp1/Bcl-2 pathway in SCM.</div></div><div><h3>Conclusions</h3><div>Naringenin attenuates the phosphorylation of Drp1 by inhibiting phosphorylation of CaMKⅡ, thereby ameliorating mitochondrial dysfunction, suppressing apoptosis, modulating myocardial electrophysiology, and ultimately reducing susceptibility to arrhythmia while improving cardiac function in SCM.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157006"},"PeriodicalIF":6.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523342","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":"Tangshen formula alleviates doxorubicin induced nephrotoxicity by regulating BAX crosstalk in podocyte","authors":"Yuxi Li ,&nbsp;Ge Hong ,&nbsp;Liang Peng ,&nbsp;Bo Zhang ,&nbsp;Shaopeng Wang ,&nbsp;Mengqi Gao ,&nbsp;Xi Dong ,&nbsp;Yuzhou Wan ,&nbsp;Jin Rong ,&nbsp;Kexu Chen ,&nbsp;Huimin Su ,&nbsp;Ping Li ,&nbsp;Yuxin Zhang ,&nbsp;Tingting Zhao","doi":"10.1016/j.phymed.2025.156858","DOIUrl":"10.1016/j.phymed.2025.156858","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX) is a widely used anticancer drug with a marked nephrotoxic effect. The Chinese medicine Tangshen Formula (TSF) has a kidney-protective effect in diabetic kidney disease patients and has been shown to attenuate kidney damage in rodents.</div></div><div><h3>Purpose</h3><div>Our study explored the putative targets and regulatory mechanisms of TSF in attenuating DOX-induced nephrotoxicity.</div></div><div><h3>Methods</h3><div>Protein factor microarray, bioinformatics analysis, MPC5 cell line were used in this work. Through the comprehensive means of biological information analysis, <em>in vitro</em> experiments, <em>in vivo</em> experiments and molecular docking, the pathological relationship between TSF and DOX induced nephrotoxic was revealed, and the potential small-molecule inhibitor were identified.</div></div><div><h3>Results</h3><div>TSF administration significantly alleviated albuminuria and histopathologic lesions. Rat renal cytokine array and GO analysis revealed that signaling pathways of TSF were closely related to apoptosis and pyroptosis. <em>In vivo</em> results verified that TSF inhibited the apoptosis and pyroptosis of DOX induced nephrotoxic rat podocyte. TSF increased levels of WT1, and nephrin, which are podocyte markers, and reduced levels of GSDMD, which is a pyroptosis marker protein in the rat kidney. Furthermore, immunofluorescence co-localization confirmed that TSF could decrease the level of BAX and increase the level of BCL2 in podocytes of DOX induced nephrotoxic rat. <em>In vitro</em>, BTSA1, which is a BAX activator, could mitigate the beneficial effects of TSF. In addition, we identified the compounds with high binding efficiency to BAX from TSF in plasma by CDOCKER, and the top three were selected for verification by western blot, ginsenoside having the best effect to MPC pyroptosis.</div></div><div><h3>Conclusion</h3><div>This study demonstrated a novel action of TSF in attenuating podocyte death by regulating BAX-mediated crosstalk between pyroptosis and apoptosis. TSF is a potential therapeutic herbal therapy against AN, and ginsenoside is the most effective inhibition of BAX levels.</div></div><div><h3>Chemical compounds</h3><div>Ginsenoside Rb1 (PubChem CID: 9898279); Notoginsenoside R1 (PubChem CID: 441934); Naringin (PubChem CID: 442428)</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156858"},"PeriodicalIF":6.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total glucosides of paeony ameliorates lupus nephritis by suppressing ZBP1-mediated PANoptosis in podocytes","authors":"Yi Wang ,&nbsp;Qian-Qian He ,&nbsp;Yan-Ting Zhu ,&nbsp;Yang Zhang ,&nbsp;Jun Yan ,&nbsp;Li-Fang Liang ,&nbsp;Xiao-Xia Zhan ,&nbsp;Song-Ling Cao ,&nbsp;Jie-Ye Huang ,&nbsp;Yan Peng ,&nbsp;Qiao-Xuan Zhang ,&nbsp;Min He ,&nbsp;Guo-Hua Li ,&nbsp;Chun-Min Kang ,&nbsp;Xian-Zhang Huang ,&nbsp;Hua Zhou ,&nbsp;Pei-Feng Ke","doi":"10.1016/j.phymed.2025.156996","DOIUrl":"10.1016/j.phymed.2025.156996","url":null,"abstract":"<div><h3>Background</h3><div>Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), lacks effective therapies because of its complex pathogenesis. PANoptosis, an integrated cell death pathway that combines apoptosis, pyroptosis, and necroptosis, has been implicated in inflammatory diseases; however, its role in LN and potential as a therapeutic target remain unexplored. Total glucosides of paeony (TGP), a traditional Chinese medicine derived from <em>Paeonia lactiflora</em> Pall, has shown promise in LN treatment due to its immunomodulatory and anti-inflammatory properties. Nevertheless, the mechanisms underlying its renoprotective effects, particularly its potential regulation of PANoptosis, are poorly understood.</div></div><div><h3>Purpose</h3><div>This study investigated the role of PANoptosis in LN pathogenesis and elucidated the therapeutic mechanisms of TGP, focusing on ZBP1-mediated podocytes PANoptosis.</div></div><div><h3>Methods</h3><div>Four mRNA microarray datasets of renal tissues from patients with LN and LN mouse models were obtained from the GEO database, and were performed with gene set enrichment analysis (GSEA) to identify PANoptosis-related pathways. Renal pathology was assessed using HE staining and proteinuria detection. Cell death was evaluated in vivo using TUNEL staining and in vitro through flow cytometry and LDH release assay. The protein levels of ZBP1 and PANoptosis markers were detected by immunoblotting and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>PANoptosis-related pathways were significantly enriched in LN kidneys. TGP treatment suppressed podocytes PANoptosis and alleviated renal injury in MRL/lpr mice. Mechanistically, TGP inhibited PANoptosis by regulating the STAT2–ZBP1 axis, with ZBP1 identified as a pivotal regulator. ZBP1 overexpression attenuated the therapeutic effects of TGP, confirming its central role in LN pathogenesis.</div></div><div><h3>Conclusion</h3><div>This study reveals ZBP1-mediated podocytes PANoptosis as a key mechanism in LN and establishes TGP as a promising therapeutic agent targeting this pathway. These findings provide a novel, clinically translatable strategy for LN treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156996"},"PeriodicalIF":6.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489550","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":"Cucurbitacin B stimulates PD-1 immunotherapy response in malignant breast cancer by covalent targeting MTCH2","authors":"Qianqian Xu ,&nbsp;Zeyu Jiang ,&nbsp;Yuqi Pan ,&nbsp;Sheng Li ,&nbsp;Zehong Cao ,&nbsp;Shengjie Hua ,&nbsp;Ruolan Yang ,&nbsp;Qinman He ,&nbsp;Hao Wu ,&nbsp;Hongmei Wen ,&nbsp;Bo Hang ,&nbsp;Hongli Yu ,&nbsp;Xinzhi Wang","doi":"10.1016/j.phymed.2025.157017","DOIUrl":"10.1016/j.phymed.2025.157017","url":null,"abstract":"<div><h3>Background</h3><div>Effective therapies for malignant breast cancer are urgently needed, as resistance and immunosuppressive microenvironments limit PD-1 blockade efficacy. The natural product Cucurbitacin B (CuB) reportedly sensitizes breast cancer to PD-1 immunotherapy, yet its molecular mechanism is undefined.</div></div><div><h3>Purpose</h3><div>Here, we sought to identify the direct molecular targets of CuB and elucidate the mechanisms responsible for its synergy with PD-1 blockade in breast cancer.</div></div><div><h3>Study design and methods</h3><div>We used Quantitative Thiol Reactivity Profiling (QTRP) to identify CuB-binding proteins. Binding interactions were validated using microscale thermophoresis (MST), cellular thermal shift assay (CETSA), and activity-based protein profiling (ABPP). The functional outcomes of CuB-protein interactions were explored using <em>in vitro</em>, e<em>x vivo</em>, and <em>in vivo</em> models, including cell lines, tumor organoids, and animal models of invasive breast cancer.</div></div><div><h3>Results</h3><div>We identified the mitochondrial outer membrane protein MTCH2, often overexpressed in aggressive breast cancer, as a direct covalent target of CuB. CuB binding to MTCH2 disrupted mitochondrial integrity, causing mitochondrial DNA (mtDNA) release into the cytosol and subsequent activation of the cGAS-STING innate immune pathway. This culminated in type I interferon production, activation of tumor-associated neutrophils, and enhanced anti-tumor immunity. Co-administration of CuB and PD-1 blockade demonstrated significant synergistic efficacy in preclinical breast cancer models.</div></div><div><h3>Conclusions</h3><div>This work elucidates a novel mechanism by which CuB enhances anti-tumor immunity: covalent targeting of MTCH2 triggers mitochondrial dysfunction and cGAS-STING pathway activation. Our findings establish MTCH2 as a key node linking mitochondrial function to tumor immunogenicity and provide a rationale for combining CuB, or potentially MTCH2 modulators, with PD-1 blockade for treating malignant breast cancer.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157017"},"PeriodicalIF":6.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510921","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-3,3′-digallate stabilizes vulnerable plaques by reprogramming metabolic homeostasis in neovascularization via HK2/TIGAR","authors":"Kuan Cen ,&nbsp;YinFei Huang ,&nbsp;Yu Xie,&nbsp;Renwei Zhang,&nbsp;Qi Cai,&nbsp;Li Zou,&nbsp;Qiaoyuan Xiang,&nbsp;Chunjiao Yang,&nbsp;YuMin Liu","doi":"10.1016/j.phymed.2025.157014","DOIUrl":"10.1016/j.phymed.2025.157014","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The leakage of vasa vasorum (VV) and intraplaque hemorrhage (IPH) pose significant risk for the instability and rupture of atherosclerosis (AS) plaques. The development of novel herbal monomers for anti-AS therapy has emerged as an increasingly promising strategy in combating cardiovascular diseases and stroke, which are frequently triggered by the rupture of vulnerable plaques.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to explore the protective effects of theaflavin-3,3′-digallate (TFDG) on plaque stability and its underlying mechanisms in preventing IPH through promoting VV maturation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A carotid vulnerable plaque mouse model was established via tandem stenosis surgery. Non-targeted metabolomics and proteomics were integrated to identify the metabolic targets of TFDG. Molecular docking, co-immunoprecipitation, and western blotting were employed to elucidate the interactions within the HK2/TIGAR/MAPK pathway. Additionally, the expression levels of inflammatory cytokines and the energy metabolism status associated with metabolic reprogramming were evaluated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;TFDG significantly modulated key serum inflammatory cytokines (IL-6, IL-1β, MCP-1, IL-4, NO) and lipid profiles (LDL, TC, HDL, TG), while suppressing AS plaque formation in Apoe&lt;sup&gt;−/−&lt;/sup&gt; mice. Quantitative analysis revealed that TFDG treatment increased fibrous cap thickness by 9.78 µm (p = 0.0085) and reduced lipid core size by 21% (p = 0.0004). Furthermore, TFDG improved the organization of the vascular lumen, restored pericyte synaptic function, and increased pericyte coverage by 8.42% (p &lt; 0.001), while concomitantly decreasing pericyte apoptosis. These effects collectively reduced the incidence of IPH from 56.25% to 26.67%, thereby enhancing plaque stability. At the molecular level, TFDG downregulated HK2 expression and rebalanced the dynamics between glycolysis and OXPHOS through the TIGAR/p38/JNK signaling axis, thereby shifting VV metabolism toward a low-energy state. This mechanism consequently inhibited excessive pathological vascular sprouting and promoted a 24% increase in pericyte quiescence and adhesion (p = 0.0037), ultimately stabilizing the microvascular network architecture within plaques. While focusing on male mice adheres to standard protocols for AS modeling, future investigations should explicitly address potential sex differences in disease progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrates that TFDG effectively inhibits AS progression via the HK2/TIGAR/MAPK axis, specifically by promoting the maturation of VV within plaques to reduce the incidence of IPH. The findings suggest that TFDG exhibits substantial potential for preventing acute cardiovascular and cerebrovascular events. The results provide promising directions and preliminary experimental evidence for future research aimed at preventing vulnerable plaque rupture.&lt;","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157014"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481373","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":"Salidroside alleviates bone cancer pain by inhibiting Th17/Treg imbalance through the AMPK/SIRT1 pathway","authors":"Kesong Zheng ,&nbsp;Chengwei Yang ,&nbsp;Mingming Han ,&nbsp;Fang Kang ,&nbsp;Juan Li","doi":"10.1016/j.phymed.2025.157000","DOIUrl":"10.1016/j.phymed.2025.157000","url":null,"abstract":"<div><h3>Background</h3><div>Bone cancer pain (BCP) remains a significant clinical challenge with poorly understood mechanisms. While Th17 and Treg cells have been implicated in pain pathways, their specific roles in BCP pathogenesis require further investigation. Salidroside (SAL), a natural compound with anti-inflammatory properties, shows potential for pain management but its mechanism in BCP is unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate SAL's analgesic effects in BCP and elucidate its mechanism of action through the AMPK/SIRT1 pathway and Th17/Treg cell regulation.</div></div><div><h3>Study design</h3><div>Experimental animal study using a well-established BCP mouse model with pharmacological interventions and cellular/molecular analyses.</div></div><div><h3>Methods</h3><div>C57BL/6 mice were used to establish a BCP model via tumor cell implantation. Behavioral tests assessed mechanical allodynia and thermal hyperalgesia. Flow cytometry analyzed spinal cord Th17/Treg populations, while Western blotting evaluated AMPK/SIRT1 pathway proteins. Pharmacological interventions included SAL administration, IL-17 neutralization, and AMPK/SIRT1 pathway modulation.</div></div><div><h3>Results</h3><div>SAL treatment significantly alleviated pain behaviors in BCP mice (<em>p</em> &lt; 0.01). Cellular analyses revealed SAL restored Th17/Treg balance by reducing Th17 markers (IL-17, RORγt, p-STAT3) and increasing Treg markers (FOXP3, p-STAT5). SAL activated the AMPK/SIRT1 pathway, while pathway inhibitors reversed SAL's therapeutic effects, confirming the mechanism.</div></div><div><h3>Conclusion</h3><div>SAL effectively alleviates BCP by modulating Th17/Treg cell differentiation through AMPK/SIRT1 pathway activation. These findings suggest SAL's potential as a novel immunomodulatory therapy for BCP management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157000"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522778","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":"Suppressing ferroptosis via modulating FTH1 by silybin for treatment of renal fibrosis","authors":"Jia-Qin Hu ,&nbsp;Cang-Qiong Ning ,&nbsp;Fang-Cao Pi ,&nbsp;Xue-Ni Cai ,&nbsp;Jian Zhou ,&nbsp;Nan Wang ,&nbsp;Li-Li Yu ,&nbsp;Hua Zhou ,&nbsp;Ying Xie","doi":"10.1016/j.phymed.2025.156937","DOIUrl":"10.1016/j.phymed.2025.156937","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis, a hallmark pathological manifestation of chronic kidney disease, arises from diverse etiological factors. While ferroptosis has emerged as a pivotal contributor to renal fibrogenesis, the regulatory mechanisms governing this process—particularly those involving iron metabolism—remain poorly characterized.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the molecular mechanism through which silybin modulates FTH1 to regulate iron homeostasis, thereby suppressing ferroptosis and attenuating fibrotic progression in renal pathology.</div></div><div><h3>Study Design</h3><div>The therapeutic efficacy of ferrostatin-1 (Fer-1) and silybin was systematically evaluated in complementary in vivo and in vitro renal fibrosis models. Mechanistic investigations employed FTH1 knockout and overexpression systems to validate its role as a therapeutic target.</div></div><div><h3>Methods</h3><div>Fibrotic inhibition was assessed histologically and via quantification of fibrotic markers. Iron ion concentrations and reactive oxygen species (ROS) levels were measured using standardized commercial assay kits. The silybin-FTH1 interaction was investigated through surface plasmon resonance (SPR) analysis.</div></div><div><h3>Results</h3><div>Silybin administration demonstrated potent ferroptosis inhibition, significantly ameliorating pathological alterations and fibrotic marker expression across experimental models. FTH1 ablation exacerbated ferroptotic cell death and fibrotic progression, whereas FTH1 overexpression conferred robust protection against renal fibrosis. Mechanistically, silybin directly bound FTH1 protein, stabilizing its expression to counteract iron overload-induced ferroptosis.</div></div><div><h3>Conclusions</h3><div>Our study unveils FTH1 stabilization as a mechanistically novel strategy to disrupt the vicious cycle of iron overload and ferroptosis in renal fibrosis, offering a superior alternative to conventional ferroptosis inhibitors targeting downstream effectors.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156937"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HIF-1α signaling pathway: A key approach to revealing the effects of Scutellaria baicalensis Georgi against lipopolysaccharide-induced spontaneous abortion","authors":"Jing-xin Gao ,&nbsp;Mei-ying Yue ,&nbsp;Jin-zhu Huang ,&nbsp;Ze-yi Guo ,&nbsp;Huan Wang ,&nbsp;Lin-wen Deng ,&nbsp;Wei-jun Ding ,&nbsp;Hang Zhou","doi":"10.1016/j.phymed.2025.157013","DOIUrl":"10.1016/j.phymed.2025.157013","url":null,"abstract":"<div><h3>Background</h3><div><em>Scutellaria baicalensis</em> Georgi (SBG) is traditionally used to prevent miscarriage through its anti-inflammatory, antioxidant, and antiapoptotic effects. However, its mechanisms in early-stage abortion (ESA) remain unclear.</div></div><div><h3>Materials and methods</h3><div>A novel network pharmacology workflow was developed to identify bioactive compounds in SBG, including the nontargeted detection of SBG components, extraction of compounds from the HERB database, manual screening and filtering. These compounds were confirmed via high-performance liquid chromatography (HPLC). Targets associated with bioactive compounds were enriched via the SWISS database, and disease-related targets were identified via GeneCards. Overlapping targets were analyzed to construct a protein - protein interaction (PPI) network, with interactions predicted via STRING and visualized via Cytoscape. Molecular docking, dynamic simulations, and transcriptomics were used to prioritize key bioactive compounds. Two ESA models were used to evaluate therapeutic effects: one induced by <em>lipopolysaccharide</em> (LPS) and the other by mifepristone (Ru486). Decidual histopathology was observed via transmission electron microscopy (TEM) and hematoxylin - eosin (HE) staining. Key targets and pathways were validated through network pharmacology, immunohistochemistry (IHC), immunofluorescence (IF), Western blotting (WB), and ELISA. Finally, the effects of SBG on pregnancy maintenance were investigated by modulating the HIF-1α pathway, with a focus on its impact on critical biomarkers identified through the screening process.</div></div><div><h3>Results</h3><div>Compared with RU486, SBG demonstrated greater efficacy in treating LPS-induced ESAs, as evidenced by lower embryo absorption rates, fewer miscarriages, and milder decidual pathological changes. Through multilevel screening, we identified 10 compounds in SBG with the highest drug potential, which were confirmed in the original plant. These compounds are predicted to specifically modulate LPS-ESA through 38 targets, influencing 525 biological processes and 126 signaling pathways. Integrated pharmacological analysis highlighted the HIF-1α signaling pathway as the key mechanism underlying the therapeutic effects of SBG on ESAs. Experiments involving HIF-1α pathway activation and inhibition confirmed that SBG inhibits decidual and embryonic cell apoptosis and hypoxia by blocking HIF-1α signal transmission.</div></div><div><h3>Conclusions</h3><div>This study established a rigorous framework for screening and analyzing the therapeutic components of SBG and revealed that SBG is specifically effective against ESAs and maternal–fetal interface inflammation through the HIF-1α signaling pathway. These findings highlight SBG as a therapeutic agent for ESA and provide a foundation for future mechanistic studies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157013"},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489546","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}