Phytomedicine最新文献

{"title":"Dahuang chuanxiong decoction against contrast-induced nephropathy: Multi-omics, crosstalk between BNIP3-mediated mitophagy and IL-17 pathway","authors":"Zhiyong Song, Jun Li, Xuezhong Gong","doi":"10.1016/j.phymed.2025.156416","DOIUrl":"10.1016/j.phymed.2025.156416","url":null,"abstract":"<div><h3>Background</h3><div>Contrast-induced nephropathy (CIN), also known as contrast-induced acute kidney injury (CI-AKI), represents a prevalent form of hospital-acquired renal injury. However, the mechanisms underlying its pathogenesis remain unclear. Based on our previous research findings, the Dahuang Chuanxiong decoction (DCH), composed of <em>Radix et Rhizoma Rhei</em> (DH) and <em>Rhizoma Chuanxiong</em> (CX), has demonstrated efficacy for inhibiting CI-AKI by attenuating oxidative stress and apoptosis in renal tubular epithelial cells. Despite these findings, the detailed mechanisms underlying the renoprotective actions have not been thoroughly clarified.</div></div><div><h3>Purpose</h3><div>The objective of this study was to screen potential targets and signaling pathways involved in inhibition of CI-AKI by DCH using multi-omics analysis and to verify whether the renoprotective mechanism of DCH is related to these identified targets or pathways through in vivo and in vitro experiments.</div></div><div><h3>Methods</h3><div>Initially, we identified the components of DCH using UPLC-Q-TOF-MS. Transcriptomics and proteomics, combined with experimental validation, were used to further elucidate the molecular mechanisms of the herbal pair in CI-AKI treatment. A CI-AKI rat model was established, and the expression levels of proteins related to mitophagy and the IL-17 signaling pathway were detected in renal tissues using immunofluorescence, immunohistochemistry, and western blotting analysis to elucidate the nephroprotective effects of DCH. Additionally, siRNA was used in the HK-2 cell model to investigate the crosstalk between the mitophagy and IL-17 signaling pathways and the impact on apoptosis when these pathways were inhibited.</div></div><div><h3>Results</h3><div>Multi-omics results revealed that the crucial signaling pathways involved were mitophagy, the MAPK signaling pathway, and the IL-17 signaling pathway. In vivo experiments indicated that contrast media (CM) led to an increase in AKI biomarkers, with upregulated expression of Parkin, BNIP3, IL-17, and p-NF-κB. Notably, pretreatment with DCH markedly reversed the expression of these proteins. Furthermore, we confirmed the importance of IL-17-mediated inflammation in the pathogenesis of CIN in vitro. We stimulated HK-2 cells with human IL-17 recombinant protein and observed an increase in the expression of p-NF-κB. Conversely, knockdown of IL-17 receptor A (IL-17RA) on the cell membrane reduced the expression of p-NF-κB and BNIP-3 under IL-17 stimulation. Additionally, the results revealed that BNIP3 knockdown reduced p-NF-κB production and alleviated the inflammation triggered by CM. The crosstalk between the two signaling pathways was initially explored.</div></div><div><h3>Conclusion</h3><div>In conclusion, these findings suggested that DCH may exert ameliorative effects on CI-AKI through a multifaceted approach, including inhibition of BNIP3-mediated mitophagy and IL-17-mediate","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156416"},"PeriodicalIF":6.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting membrane integrity and imidazoleglycerol-phosphate dehydratase: Sanguinarine multifaceted approach against Staphylococcus aureus biofilms","authors":"Qianwei Qu , Xingyu Huang , Zhenxin Zhu , Jun Wang , Mengmeng Zhao , Wenqiang Cui , Yadan Zheng , Yanyan Liu , Xueying Chen , Zhiyun Zhang , Na Dong , Chunliu Dong , Yanhua Li","doi":"10.1016/j.phymed.2025.156428","DOIUrl":"10.1016/j.phymed.2025.156428","url":null,"abstract":"<div><h3>Background</h3><div><em>Staphylococcus aureus</em> is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the <em>Sanguinaria canadensis L.</em> (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti-<em>S. aureus</em> effect. Nevertheless, the specific mechanism of action of sanguinarine against <em>S. aureus</em> biofilms remains unexplored.</div></div><div><h3>Purpose</h3><div>The objective of this study was to elucidate the target site of sanguinarine in <em>S. aureus</em>, as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics.</div></div><div><h3>Methods</h3><div>Initially, we assessed the <em>in vitro</em> anti-<em>S. aureus</em> properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with <em>S. aureus</em> biofilm formation was preliminarily analyzed <em>in vitro</em>. Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated <em>in vivo</em> using mouse models of biofilm and bacteremia.</div></div><div><h3>Results</h3><div>Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering <em>S. aureus</em> biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the <em>S. aureus</em> load in mouse organs and the formation of biofilm on the surface of implants <em>in vivo</em> without any resistance.</div></div><div><h3>Conclusions</h3><div>In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of <em>S. aureus</em> and targeting IGPD. These findings suggest that sanguinarine holds po","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156428"},"PeriodicalIF":6.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067380","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":"Targeting pyroptosis: A novel strategy of ginseng for the treatment of diabetes and its chronic complications","authors":"Ke Li ,&nbsp;Ya-jun Wang ,&nbsp;Chen Chen ,&nbsp;Xiao-jie Wang ,&nbsp;Wei Li","doi":"10.1016/j.phymed.2025.156430","DOIUrl":"10.1016/j.phymed.2025.156430","url":null,"abstract":"<div><h3>Background</h3><div>Pyroptosis is a recently identified form of programmed cell death that plays a crucial role in the pathogenesis and progression of diabetes and associated chronic complications, while the occurrence mechanism remains unclear. Ginseng (<em>Panax Ginseng</em> C. A. Mey.) is a valuable traditional medicinal material with proved therapeutic effects on prevention and treatment of diabetes and diabetic complications. Targeting pyroptosis pathway has become a focus of study for ginseng in improvement of diabetes and related chronic complications.</div></div><div><h3>Purpose</h3><div>The review aims to elucidate the happening mechanism of pyroptosis in diabetes and diabetic chronic complications, evaluate the effects of ginseng and its active components on diabetes and its chronic complications via pyroptosis-related pathways, and provide a new perspective for the management of diabetes.</div></div><div><h3>Methods</h3><div>We conducted the literature retrieval with PubMed, Web of Science, and ScienceDirect databases in a systematic manner (up to August 2024). The keywords included pyroptosis, diabetes, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic neuropathy, ginseng, ginseng extract, and ginsenoside. The obtained literatures were comprehensively sorted out.</div></div><div><h3>Results</h3><div>Oxidative stress, endoplasmic reticulum stress (ERS), and inflammatory responses were primary contributors to pyroptosis in diabetes and associated chronic complications. In addition, some RNA molecules (miRNAs, circRNAs, and lncRNAs) also contributed to pyroptosis under hyperglycemia. The signaling pathways mainly included Nrf2/HO-1, IκB/NF-κB/NLRP3, NOX1/NOX4/TXNIP, and P2X7R/TXNIP/NLRP3. Ginseng extracts, some ginsenosides and flavonoid (Quercetin) could exert anti-diabetic effect by regulating pyroptosis-related pathways. We also discussed the toxicity, side effects and clinical applications of ginseng.</div></div><div><h3>Conclusion</h3><div>In summary, this review elucidates the happening mechanisms of pyroptosis in diabetes and associated chronic complications, and summarizes published studies about ginseng and its active ingredients in improving diabetes by regulating pyroptosis-related pathways. However, almost all researches are limited to animal and cell experiments, and more clinical trials are required to prove the therapeutic effect of ginseng on diabetes by targeting pyroptosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156430"},"PeriodicalIF":6.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075193","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":"Bibliometric analysis of literature on natural medicines against chronic kidney disease from 2001 to 2024","authors":"Xiaoqing Shi ,&nbsp;Hongmei Yin ,&nbsp;Xiaodan Shi","doi":"10.1016/j.phymed.2025.156410","DOIUrl":"10.1016/j.phymed.2025.156410","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a globally common and progressive disease. There has been few bibliometric study to analyze the status, hot spots, and trends in the field of natural medicines (NMs) against CKD.</div></div><div><h3>Purpose</h3><div>To comprehensively understand the status, hot spots, and trends in the field of NMs against CKD.</div></div><div><h3>Methods</h3><div>The documents concerning NMs against CKD are extracted from the Web of Science Core Collection database (WOSCC). The literature analysis was conducted using VOSviewer 1.6.20 and CiteSpace 6.3.R1 software.</div></div><div><h3>Results</h3><div>In total, 641 publications were encompassed, which were produced by 3 548 authors and 823 organizations, 241 journals, and 56 countries/regions. The most productive author, institution, country, and journal were Li, Ping, Nanjing University of Chinese Medicine, China, and Journal of Ethnopharmacology, respectively. The first high-cited article was published in Medicinal Research Reviews with 457 citations authored by Huang and colleagues in 2007. Oxidative stress, anti-inflammatory, renal fibrosis, and gut microbiota were the emerging keywords. Rhubarb, Astragalus, Angelica, and Cordyceps, which contain anthraquinones, cordycepin, adenosine, or various polysaccharides, are promising NMs to prevent or treat CKD.</div></div><div><h3>Conclusion</h3><div>Currently, the main hot spot is the elucidation of cellular and molecular mechanisms using novel technologies such as network pharmacology, molecular docking, and experimental validation. Future studies are needed to focus on the inherent molecular mechanisms and clinical applications. In addition, potential side effects of the bioactive compounds cannot be ignored.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156410"},"PeriodicalIF":6.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated identification and mechanism exploration of bioactive ingredients from Salvia miltiorrhiza to induce vascular normalization","authors":"Cheng Qian ,&nbsp;Ying Huang ,&nbsp;Shan Zhang ,&nbsp;Chunmei Yang ,&nbsp;Weiwei Zheng ,&nbsp;Weiwei Tang ,&nbsp;Guiping Wan ,&nbsp;Aiyun Wang ,&nbsp;Yin Lu ,&nbsp;Yang Zhao","doi":"10.1016/j.phymed.2025.156427","DOIUrl":"10.1016/j.phymed.2025.156427","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The clinical management of ischemic disease and cancer is complex, with disruptions in local vascular function and tumor angiogenesis contributing to blood stasis, which complicates treatment strategies. &lt;em&gt;Salvia miltiorrhiza&lt;/em&gt;, a natural product, is known to restore vascular structure and function. However, its specific roles in concurrently addressing ischemic disease and cancer within the same organism remain poorly understood.&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 material basis, pharmacological effects, and underlying mechanisms of &lt;em&gt;Salvia miltiorrhiza&lt;/em&gt; extract (SME) in promoting blood flow recovery in ischemic hindlimbs and inducing tumor vascular normalization.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The pharmacological effects of SME were evaluated in a mouse model combining ischemic hindlimbs and tumors. Mice were administered low (SME-L) or high (SME-H) doses of SME daily, and the gastrocnemius muscle mass and tumor vascular structure were assessed. Laser Doppler perfusion imaging (LDPI) was used to monitor hindlimb blood flow recovery and tumor vascular perfusion. The pharmacokinetics of the key bioactive constituents in SME were characterized by liquid chromatography-mass spectrometry (LC-MS). Interactions between SME's active compounds and predicted targets were investigated using molecular docking, microscale thermophoresis (MST), and luciferase reporter assays. The synergistic effects of the primary components, Tanshinone I (Tan I) and Salvianolic acid A (Sal A), were analyzed through tube formation assays, enzyme-linked immunosorbent assays (ELISA), immunofluorescence staining, and western blot.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Phytochemical profiling revealed that SME contains several active compounds, including Danshensu, Sal A, Sal B, Tan IIA, and Tan I. SME treatment reduced the frequency of necrotic toes, increased muscle mass, and alleviated hypoxia in the gastrocnemius muscle. SME significantly improved tumor vascular perfusion and notably enhanced pericyte coverage and basement membrane integrity. Pharmacokinetic analysis identified Tan I and Sal A as the key bioactive components that promote vascular normalization. Tan I inhibited FoxO1, preventing endothelial cell activation induced by angiopoietin 2 (Ang2), while Sal A bound to Ang2, facilitating Tie2 activation mediated by Ang1. Both in vitro and in vivo results demonstrated that the combination of Tan I and Sal A exerted a synergistic therapeutic effect on correcting abnormal blood vessels in ischemic hindlimbs and tumors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our study innovatively revealed a reliable mouse model wherein the Ang2/Tie2 signaling cascade disrupted the endothelial homeostasis to aggravate the progression of hindlimb ischemia and tumor angiogenesis. This balance can be rescued by the combination therapy of Tan I and Sal A that were both from SME, leading to the occurrence of vascu","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156427"},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075066","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":"Juglone induces ferroptotic effect on hepatocellular carcinoma and pan-cancer via the FOSL1-HMOX1 axis","authors":"Chuyu Wang ,&nbsp;Ying Zhao ,&nbsp;Yingfei Peng ,&nbsp;Wei Chen ,&nbsp;Jie Zhu ,&nbsp;Chenzheng Gu ,&nbsp;Ran Huo ,&nbsp;Lin Ding ,&nbsp;Yu Liu ,&nbsp;Te Liu ,&nbsp;Chunyan Zhang ,&nbsp;Wenjing Yang ,&nbsp;Hao Wang ,&nbsp;Wei Guo ,&nbsp;Beili Wang","doi":"10.1016/j.phymed.2025.156417","DOIUrl":"10.1016/j.phymed.2025.156417","url":null,"abstract":"<div><h3>Background</h3><div>Drug therapy plays an essential role in the management of hepatocellular carcinoma (HCC). Recently, the use of natural products to suppress tumor cells has emerged as a promising direction for drug development. Juglone, a natural compound, exhibits anticancer activities across various cancer types. However, the precise mechanism underlying the anticancer effect of juglone, especially in HCC, remains elusive.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the potential inhibitory effects of juglone on HCC and pan-cancer, as well as elucidate the underlying mechanism.</div></div><div><h3>Methods</h3><div>Cell Counting Kit-8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration. Cell cycle distribution was assessed by flow cytometry. The <em>in vivo</em> effect of juglone on HCC was evaluated by establishing the HCC xenograft mice model. RNA sequencing and inhibitors targeting diverse modes of programmed cell death were applied to uncover the form of juglone-induced cell death. Integrated transcriptomic, and proteomic analyses unveiled the underlying mechanism. The dual-luciferase reporter assay was employed to verify the findings. The pan-cancer value of juglone was assessed using TCGA database analysis and cellular assays.</div></div><div><h3>Results</h3><div>Juglone suppressed HCC growth via ferroptosis <em>in vitro</em> and <em>in vivo</em>, which is evidenced by increased levels of iron, lipid peroxidation (LPO), reactive oxygen species (ROS), malondialdehyde (MDA), and decreased levels of glutathione (GSH). Omic analyses, gene silencing and functional analyses showed the upregulated HMOX1 and FOSL1 were the key effector molecule and transcriptional factor in juglone-induced ferroptosis, respectively. The binding site of FOSL1 at the promoter of HMOX1 was identified. Juglone could induce ferroptosis in pan-cancer by activating the FOSL1-HMOX1 axis.</div></div><div><h3>Conclusion</h3><div>Our findings, for the first time, demonstrate that juglone effectively inhibits tumor growth by inducing FOSL1-HMOX1-dependent ferroptosis, thereby offering a promising strategy for the development of anticancer drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156417"},"PeriodicalIF":6.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350494","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":"Exploring the active components and potential mechanisms of Zhimu-Huangbai herb-pair in the treatment of depression","authors":"Xia Lei ,&nbsp;Deping Zhao ,&nbsp;Tongtong Chen ,&nbsp;Qing Li ,&nbsp;Ao Xue ,&nbsp;Zhuoyi Hu ,&nbsp;Fan jia ,&nbsp;Xiaoliang Li","doi":"10.1016/j.phymed.2025.156365","DOIUrl":"10.1016/j.phymed.2025.156365","url":null,"abstract":"<div><h3>Background</h3><div>The Zhimu-Huangbai herb-pair (ZB) is commonly used to treat depression. Previous research has verified that ZB is effective as an antidepressant. Nevertheless, its active components and potential mechanism still require further elucidation.</div></div><div><h3>Purpose</h3><div>This study aims to analyze the compounds of ZB penetrating into the brain using UPLC-MS and investigate the potential mechanisms of ZB in the treatment of depression through <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Methods</h3><div>The compounds of ZB that penetrate into the brain were identified using the UPLC-MS method. Network pharmacology analysis was employed to predict the therapeutic targets and mechanisms of the compounds of ZB in the brain for the treatment of depression. Subsequently, the molecular docking method was used to analyze the binding between active compounds and target proteins. Rat depression models induced by CUMS were used to investigate the impact of ZB on depression. Finally, the mechanism of ZB treatment for depression was investigated using the LPS-induced BV2 cell inflammation model.</div></div><div><h3>Results</h3><div>A total of 17 compounds were identified in ZB that crossed the blood-brain barrier (BBB). The network pharmacological analysis showed that the anti-depressant mechanism of ZB is closely related to inflammatory cytokines, including TNF and IL-6. Furthermore, KEGG and PPI analyses demonstrated that ZB regulates the microglia M1/M2 phenotypic polarization by modulating inflammation-related pathways. ZB was found to improve depression-like behavior <em>in vivo</em>. The molecular docking indicated that the compounds in ZB that penetrate into the brain have a strong binding ability to RELA and PPAR-γ. ZB inhibited the expression of p-p65 and increased the expression of PPAR-γ in the mPFC. By rebalancing the ratio of pro-inflammatory/anti-inflammatory cytokines, ZB was able to reduce neuroinflammation in the mPFC and hippocampus regions. The immunofluorescence results showed that ZB-containing serum reduced M1 polarization induced by LPS in BV2 cells.</div></div><div><h3>Conclusion</h3><div>This study reveals that ZB effectively alleviates depression by regulating the M1/M2 phenotypic polarization of microglial cells. The mechanism may be that the active compounds of ZB reduce M1 phenotypic polarization by inhibiting P65 and increase M2 phenotypic polarization by promoting PPARγ.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156365"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101384","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":"Ginsenoside Rh2(S) maintains cytoskeleton homeostasis and inhibits pyroptosis to resist cisplatin-induced cardiotoxicity through FGFR1/HRAS axis","authors":"Hongbo Teng ,&nbsp;Shuai Huang ,&nbsp;Xialin Sun ,&nbsp;Haohao Wang ,&nbsp;Xv Wang ,&nbsp;Wenxin Zhang ,&nbsp;Haijing Wang ,&nbsp;Shurong Qu ,&nbsp;Zhengxuan Yu ,&nbsp;Yan Zhao ,&nbsp;Shuangli Liu","doi":"10.1016/j.phymed.2025.156425","DOIUrl":"10.1016/j.phymed.2025.156425","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer undergoing cisplatin chemotherapy frequently experience cardiotoxic side effects that significantly affect their prognosis and survival rates. Our study found that Panax ginseng root extract exerted a significant protective effect against cisplatin-induced myocardial cell injury.</div></div><div><h3>Purpose</h3><div>The present study aims to elucidate the underlying mechanisms by which the bioactive components of Panax ginseng mitigate cisplatin-induced cardiotoxicity (CIC).</div></div><div><h3>Methods</h3><div>In vitro, the candidate active components were screened by network pharmacological prediction and in neonatal rat ventricular myocytes (NRVMs), and their mechanisms of action were verified by transcriptome sequencing, western blotting, gene overexpression, immunoprecipitation, immunofluorescence, and cellular thermal shift assays. A C57BL/6 CIC mouse model was established to verify the protective effects of the candidate components and the in vivo mechanism of the candidate components.</div></div><div><h3>Results</h3><div>Through network pharmacology prediction and cellular activity screening of ginseng root compounds, ginsenoside Rh2(S) (Rh2) was identified as a significant active component. Transcriptomic, in vitro, and in vivo experiments demonstrated that Rh2 can activate the Pak1/Limk1/cofilin phosphorylation pathway, thereby inactivating the actin-severing protein cofilin and protecting cardiomyocytes from cisplatin-induced actin depolymerization. Additionally, Rh2 suppressed the ROS/caspase-3/GSDME pathway to inhibit cisplatin-induced pyroptosis. Furthermore, co-immunoprecipitation and overexpression experiments confirmed that Rh2 activated the FGFR1/HRAS axis, thereby simultaneously regulating the two aforementioned pathways to combat CIC.</div></div><div><h3>Conclusions</h3><div>This study demonstrated for the first time that Rh2 is the main active component in Panax ginseng that maintains cytoskeletal homeostasis and inhibits pyroptosis by regulating the FGFR1/HRAS pathway to resist CIC. This study aimed to provide a theoretical basis for expanding the targets and pathways of CIC treatment, and for the development of related drugs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156425"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067251","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":"Targeting the NF-κB p65-MMP28 axis: Wogonoside as a novel therapeutic agent for attenuating podocyte injury in diabetic nephropathy","authors":"Xiandeng Li ,&nbsp;Shuyan Zhao ,&nbsp;Jing Xie ,&nbsp;Mi Li ,&nbsp;Shuangmei Tong ,&nbsp;Jing Ma ,&nbsp;Rui Yang ,&nbsp;Qinjian Zhao ,&nbsp;Jian Zhang ,&nbsp;Ajing Xu","doi":"10.1016/j.phymed.2025.156406","DOIUrl":"10.1016/j.phymed.2025.156406","url":null,"abstract":"<div><h3>Background</h3><div>Although recent progress provides mechanistic insights into diabetic nephropathy (DN), effective treatments remain scarce. DN, characterized by proteinuria and a progressive decline in renal function, primarily arises from podocyte injury, which impairs the glomerular filtration barrier. Wogonoside, a bioactive compound from the traditional Chinese herb <em>Scutellaria baicalensis</em>, has not been explored for its role in DN.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the therapeutic effects of wogonoside on podocyte injury in DN and its molecular mechanisms.</div></div><div><h3>Methods</h3><div>The effects of wogonoside were examined using HFD/STZ-induced DN mouse models and high glucose (HG)-induced MPC-5 cells. Oxidative stress and inflammation markers were analyzed via Western blot and RT-qPCR. Wogonoside targets were identified through DARTS-MS and validated by SPR, molecular docking, alanine scanning, and CETSA. RNA-Seq analysis was employed to identify downstream targets, and the p65-MMP28 axis was explored through <em>p65</em> knockdown and overexpression studies. The regulatory effect of p65 on Mmp28 was confirmed through dual-luciferase reporter assays and ChIP-qPCR.</div></div><div><h3>Results</h3><div>Wogonoside treatment significantly reduced oxidative stress and inflammation in vivo and in vitro. Mechanistic studies identified p65 as a direct target of wogonoside, with SPR confirming a strong binding affinity (<em>K_D</em> = 25.05 μM). Molecular docking and alanine scanning identified LYS221 as a critical binding site, which was further supported by CETSA using the p65 K221A mutant. RNA-Seq analysis revealed <em>Mmp28</em> as a downstream effector of p65 involved in HG-induced podocyte injury. Functional studies demonstrated that wogonoside's protective effects on antioxidant and inflammatory pathways are mediated via the p65-MMP28 axis. Dual-luciferase reporter assays revealed that p65 regulates <em>Mmp28</em> transcription, and ChIP-qPCR confirmed its direct promoter binding.</div></div><div><h3>Conclusions</h3><div>This study highlights wogonoside as a promising candidate for the treatment of podocyte injury in DN by targeting the NF-κB p65-MMP28 signaling axis. These findings provide novel insights into wogonoside's therapeutic potential and its molecular mechanisms, paving the way for its further development as a DN intervention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156406"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xin-Ji-Er-Kang balances mitochondrial fusion and fission to protect cardiomyocytes in mice with heart failure by regulating the ERα/SIRT3 pathway","authors":"Wei-wei Cai ,&nbsp;Yuan-yuan Qin ,&nbsp;Fei Ge ,&nbsp;Qing Zhou ,&nbsp;Lei Huang ,&nbsp;Pang-bo Yang ,&nbsp;Jie Xia ,&nbsp;Ke-ke Li ,&nbsp;Yi-fan Hou ,&nbsp;Jia-min Wu ,&nbsp;Ding-Yan Wang ,&nbsp;Ya You ,&nbsp;Wen-jie Lu ,&nbsp;Shan Gao","doi":"10.1016/j.phymed.2025.156420","DOIUrl":"10.1016/j.phymed.2025.156420","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial dynamics imbalance is an essential pathological mechanism in heart failure (HF). The Chinese herbal formula Xin-Ji-Er-Kang (XJEK) has demonstrated good therapeutic effects in various cardiovascular disease models. However, whether XJEK treats HF by regulating mitochondrial dynamics homeostasis and its specific molecular mechanisms remain elusive.</div></div><div><h3>Purpose</h3><div>To investigate the effect of XJEK on restoring the disrupted mitochondrial dynamics homeostasis in HF and elucidate the potential regulatory mechanism.</div></div><div><h3>Study-design/methods</h3><div>A mouse model of myocardial ischemia-reperfusion (MIR)-induced HF was established to assess the cardioprotection of XJEK. Subsequently, network pharmacology was employed to predict the mechanism by which XJEK treated HF. Moreover, gene silencing was employed to explore the potential mechanisms behind the cardioprotective effects of XJEK in AC16 cells subjected to hypoxia/reoxygenation (H/R).</div></div><div><h3>Results</h3><div>XJEK treatment significantly attenuated myocardial fibrosis and ameliorated ventricular remodeling in post-MIR-induced HF mice. Network pharmacology analysis identified the estrogen receptor α (ERα) as a key regulator of XJEK-mediated cardioprotection. XJEK disordered mitochondrial dynamics in the hearts of MIR-induced HF mice. In addition, XJEK restored mitochondrial fusion-fission imbalance and facilitated ERα nuclear translocation to up-regulate sirtuin 3 (SIRT3) expression in the hearts of MIR-induced HF mice and H/R-induced AC16 cells. Notably, ERα depletion in cardiomyocytes completely abrogated the cardioprotective effects of XJEK.</div></div><div><h3>Conclusion</h3><div>XJEK safeguards the hearts in mice with MIR-induced HF by facilitating ERα nuclear translocation to up-regulate SIRT3 expression to rescue the mitochondrial fusion-fission imbalance. This study establishes a new theoretical basis for treating HF with XJEK.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156420"},"PeriodicalIF":6.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304848","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}