Journal of ethnopharmacology最新文献

{"title":"Epimedium and its chemical constituents in cancer treatment: A comprehensive review of traditional applications, antitumor effects, pharmacokinetics, delivery systems, and toxicology","authors":"Shujun Wang , Haichao Wang , Yinghan Zhang , Guoliang Yin , Xin Zhang , Fengxia Zhang","doi":"10.1016/j.jep.2025.119738","DOIUrl":"10.1016/j.jep.2025.119738","url":null,"abstract":"<div><h3>Ethnic pharmacological relevance</h3><div><em>Epimedium</em>, recognized within traditional Chinese medicine (TCM) as a tonic, is noted for its role in enhancing kidney Yang, fortifying muscles and bones, and alleviating wind and dampness. It also exhibits therapeutic and preventive properties against cancer. This study systematically analyzes the botany, traditional uses, principal chemical components, antitumor mechanisms, pharmacokinetics, toxicology, and drug delivery systems of <em>Epimedium</em>. It aims to further prospect the antitumor capabilities of <em>Epimedium</em> based on existing research.</div></div><div><h3>Aim of the study</h3><div>This review aims to explore the traditional antitumor applications of <em>Epimedium</em> and the contemporary pharmacological actions of its chemical components, providing robust theoretical support for further elucidating Epimedium's antitumor mechanisms. It also offers a comprehensive view for the research and development of cancer treatments involving <em>Epimedium</em>.</div></div><div><h3>Materials and methods</h3><div>We conducted searches in classical Chinese herbal medicine resources, PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) for studies on the antitumor effects of <em>Epimedium</em> and its components. Existing experimental and clinical studies were systematically summarized and analyzed to understand the mechanisms by which <em>Epimedium</em> treats cancer.</div></div><div><h3>Results</h3><div>In the realm of Chinese medicine, <em>Epimedium</em> is recognized for its cancer-treating capabilities. Besides its traditional effects, flavonoids and polysaccharides from <em>Epimedium</em> can inhibit tumor cell proliferation, induce apoptosis, promote autophagy, reduce drug resistance, and improve the tumor immune microenvironment (TIM), addressing cancers of the digestive system, such as liver, colon, and gastric cancers, and of the reproductive system, including breast, cervical, and ovarian cancers. Although the bioavailability of Epimedium flavonoids is low due to rapid absorption and elimination, the use of nanotechnology has significantly enhanced the efficacy of targeted antitumor therapies. Nevertheless, the mechanisms and safety of <em>Epimedium</em> in cancer treatment merit further investigation. Despite its low acute and long-term toxicity, additional research is required to clarify its hepatotoxicity, particularly in vivo, and to further explore its metabolic pathways, distribution, and mechanisms within the body.</div></div><div><h3>Conclusion</h3><div><em>Epimedium</em> and its chemical constituents have been shown to inhibit tumor initiation and progression, however, further clinical studies are required to validate these findings. Despite its potential, significant limitations remain in the current research on <em>Epimedium</em>, necessitating more comprehensive studies on its potent bioactive components, potential pharm","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119738"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the pharmacological substance basis and efficacy evaluation of fufang she-she-cao (Hedyotis diffusa formula) in repressing gastric cancer","authors":"Da-Hong Chen ,&nbsp;Peng-Juan Mao ,&nbsp;Wen-Jing Diao ,&nbsp;Jia-Qi Lu ,&nbsp;Shi-Lan Wu ,&nbsp;Qin Li","doi":"10.1016/j.jep.2025.119711","DOIUrl":"10.1016/j.jep.2025.119711","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Due to the low early diagnosis rate and strong heterogeneity, gastric cancer (GC), a malignant tumor of the digestive tract, still poses a serious threat to human health. Fufang She-She-Cao (<em>Hedyotis diffusa</em> formula, HDF), a classic ancient prescription used in Shanghai General Hospital, has been applied to prevent and treat precancerous lesions of GC for many years. However, it lacks systematic preclinical studies.</div></div><div><h3>Aim of the study</h3><div>The purpose of this study is to explore the pharmacodynamic material basis of HDF, evaluate its efficacy in GC, and elucidate its underlying pharmacological mechanisms.</div></div><div><h3>Materials and methods</h3><div>The chemical composition fingerprint of HDF was characterized by UPLC-HRMS. Based on the chemical components identified in HDF, a content determination method was established using UPLC-MS technology. “Compounds-target-disease' network was constructed by network pharmacology analysis. The inhibitory effect of HDF on GC in vitro was detected by CCK8, colony formation assay, EdU assay, wound healing assay, transwell assay and other methods. Nude mice were used to construct a cell-derived xenograft tumor model to evaluate the anti-GC efficacy of HDF in vivo. Preliminary exploration and verification of its potential pharmacological molecular mechanism through Western blot.</div></div><div><h3>Results</h3><div>HDF contains 1616 chemical components, belonging to 120 categories, including Quercetin, Engelitin and Dioscin, etc. A content detection method has been successfully established for these three components, with specificity, linear relationship, precision, and stability all meeting the content determination requirements. HDF significantly inhibited the proliferation, migration, and invasion abilities of GC cells, induced apoptosis of GC cells, and also had a significant anti-tumor effect in vivo. Based on the chemical component targets obtained by network pharmacology analysis, GO and KEGG analysis of core targets showed that they were involved in multiple classic tumor-related signaling pathways and cellular biological processes. WB results showed that HDF could significantly reduce Akt protein expression, enhance GSK3β phosphorylation and degradation of β-catenin, promote DKK1 protein expression, competitively bind to Wnt protein, and collaboratively reduce the activity of Wnt/β-catenin pathway.</div></div><div><h3>Conclusions</h3><div>HDF has the advantages of diverse active ingredients and multiple therapeutic targets, and it could inhibit the activity of the tumor-related classic signaling pathway Wnt/β-catenin to exert anti-GC effects. This study is the first to systematically evaluate the anti-GC effect of HDF and preliminarily explain its pharmacological mechanism, providing solid theoretical support for the clinical prevention and treatment of GC with HDF.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119711"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niuhuang jiedu prescription alleviates realgar-induced dopaminergic and GABAergic neurotoxicity in Caenorhabditis elegans","authors":"Ying Wang ,&nbsp;Linjuan Du ,&nbsp;Lingyue Zou ,&nbsp;Xiaowei Chen ,&nbsp;Jiansheng Zhu ,&nbsp;Qinli Ruan ,&nbsp;Guochun Li ,&nbsp;Ju Dong","doi":"10.1016/j.jep.2025.119721","DOIUrl":"10.1016/j.jep.2025.119721","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Niuhuang Jiedu (NHJD) is a Chinese medicine prescription containing realgar (As₂S₂), which is neurotoxic, and seven other traditional Chinese medicines (TCMs). However, whether the multiple TCMs contained in NHJD can mitigate the neurotoxicity of realgar is yet to be elucidated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the effect of NHJD on realgar-induced neurotoxicity and elucidate its underlying mechanisms.</div></div><div><h3>Material and methods</h3><div><em>Caenorhabditis elegans</em> was treated with realgar suspension (1–8 mg/mL) for 48 h. Transgenic nematode strains labeled with green fluorescent protein were used to evaluate neuronal structural damage. Locomotion and perception behaviors were assessed by measuring head thrashes, body bends, and chemotaxis. Oxidative stress was determined by detecting reactive oxygen species (ROS), lipofuscin, and glutathione-S-transferase-4 (GST-4) levels. Subsequently, a quantitative reverse transcription–polymerase chain reaction was employed to analyze gene expression associated with oxidative stress, whereas the role of the p38 MAPK pathway was investigated using KU25 nematodes. Finally, arsenic species in the nematodes were estimated using high-performance liquid chromatography–atomic fluorescence spectrometry. Data analysis was performed using analysis of variance or rank tests with SPSS 26.0.</div></div><div><h3>Results</h3><div>Treatment of nematodes with 8 mg/mL realgar resulted in significant damage to dopaminergic and GABAergic neurons, impaired locomotor and perceptual behavior (at 4–8 mg/mL), and induced oxidative damage (at 2–8 mg/mL). A neuron-defective model was established using 8 mg/mL realgar to gauge the effects of NHJD on realgar-induced damage. The findings indicated that NHJD, containing the same dose of realgar, significantly alleviated neuronal damage and neurobehavioral impairment and increased ROS, lipofuscin, and GST-4 levels. In addition, NHJD reduced the expressions of oxidative stress-related genes (<em>gst-4, skn-1, gcs-1, gss-1, ctl-2, ctl-3,</em> and <em>sod-1</em>) compared with realgar alone. Nonetheless, significant differences in <em>skn-1</em> expression, neurobehavior, ROS, or lipofuscin levels were not observed between the realgar and NHJD groups in KU25 nematodes. Moreover, arsenic methylation metabolites were not identified in the nematodes.</div></div><div><h3>Conclusions</h3><div>The multiple TCMs contained in NHJD effectively mitigated realgar-induced dopaminergic and GABAergic neurotoxicity in nematodes, and <em>pmk-1</em> may play a crucial role in NHJD's alleviating realgar-induced neurotoxicity via the p38 MAPK signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119721"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the molecular mechanism of Buzhong Yiqi Decoction for tendon bone healing on the basis of network pharmacology, molecular docking and experimental validation","authors":"Shibo Xu ,&nbsp;Yihang Yu ,&nbsp;Qizhong Xie ,&nbsp;Xiao Liu ,&nbsp;Anyang Zhang ,&nbsp;Hong Tang ,&nbsp;Zhiquan Zhu ,&nbsp;Xuting Bian ,&nbsp;Lin Guo","doi":"10.1016/j.jep.2025.119726","DOIUrl":"10.1016/j.jep.2025.119726","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Buzhong Yiqi Decoction (BD), a traditional formula in Chinese medicine, is clinically and historically recognized for its effectiveness in reducing physical fatigue and promoting strength, as well as enhancing bone remodeling. Nevertheless, its specific molecular mechanisms related to bone formation have yet to be thoroughly characterized.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the effects and mechanisms of BD on osteogenesis in bone marrow mesenchymal stem cells and in a model of tendon-bone junction injury in mice.</div></div><div><h3>Materials and methods</h3><div>By establishing a mouse model of tendon-bone junction injury, the pathological morphology of the tendon-bone junction in mice was observed. Determining the mechanism of action of BD in regulating osteogenic differentiation through network pharmacology and molecular docking. Flow analysis and osteogenic induction assay were utilized to verify the effect of BD in promoting BMSCs osteogenic differentiation in vitro. In vivo experiments were performed to validate the impact of BD in improving healing after tendon-bone junction injury in mice by promoting osteogenic differentiation.</div></div><div><h3>Results</h3><div>Bone loss at the heel bone end is an essential pathophysiologic process in the natural healing process after injury to the tendon-bone junction. Using network pharmacology and molecular docking, we identified the PI3K-Akt signaling pathway as a critical mediator of BD-induced osteogenic differentiation. In vitro experiments demonstrated that BD promoted BMSC osteogenesis, while in vivo assays confirmed the enhancement of tendon-bone healing in mice models.</div></div><div><h3>Conclusion</h3><div>These results suggest that BD can effectively promote tendon-bone repair, with the PI3K-Akt pathway playing a crucial role in its therapeutic effects, positioning BD as a promising candidate for improving musculoskeletal injury recovery.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119726"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining network pharmacology and transcriptomics to validate and explore the efficacy and mechanism of Huayu Wan in treating non-small cell lung cancer","authors":"Tangke Gao ,&nbsp;Shaopu Hu ,&nbsp;Min Jiang ,&nbsp;Guangyin Ou ,&nbsp;Ruikang Zhong ,&nbsp;Jingyi Sun ,&nbsp;Qian Yang ,&nbsp;Kaiwen Hu ,&nbsp;Lei Gao","doi":"10.1016/j.jep.2025.119724","DOIUrl":"10.1016/j.jep.2025.119724","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Huayu Wan (HYW), a traditional Chinese medicine prescription widely used in the clinical treatment of advanced lung cancer, has been clinically proven to effectively inhibit the progression of pulmonary tumors and improve patients' quality of life. However, its specific components and potential anti-cancer molecular mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>To explore the active ingredients of HYW and predict its effective targets and pathways against non-small cell lung cancer (NSCLC) using a combination of network pharmacology and transcriptomics. These predictions were subsequently validated through in vitro and <em>in vivo</em> experiments, providing a theoretical basis for its anti-cancer mechanism.</div></div><div><h3>Materials and methods</h3><div>We first established a LEWIS tumor-bearing mouse model to evaluate the dose-response relationship and inhibitory effect of HYW in NSCLC. Using Ultra-High Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UHPLC-Q-Orbitrap-HRMS), we comprehensively explored the material basis of HYW's therapeutic effect on lung cancer. Combining network pharmacology and transcriptomics, we further verified the potential molecular targets and pathways of HYW. Finally, in vitro and <em>in vivo</em> molecular biological experiments were conducted to validate the predicted results.</div></div><div><h3>Results</h3><div>HYW exhibited a dose-dependent tumor inhibitory effect in the LEWIS tumor-bearing mouse model. Comprehensive qualitative analysis of the chemical components of HYW through UHPLC-Q-Orbitrap HRMS identified 39 major active ingredients, including geniposide, quercetin, taurine, and paeoniflorin. The constructed HYW active compound-NSCLC target network revealed 48 core targets, which may play a critical role in HYW's anti-NSCLC therapeutic effects. Combining transcriptomic data from mouse tumor tissues, four core targets—Pik3ca, Akt1, Pdk1, and VEGFA—were identified, along with the key signaling pathway PI3K/AKT/VEGFA. Immunofluorescence results indicated that HYW dose-dependently inhibited the positive expression of Ki67 in mouse tumor tissues. <em>In vitro</em> experiments showed that HYW significantly suppressed the proliferation, migration, and invasion abilities of H1299 and A549 cells. qRT-PCR and Western blot analyses demonstrated that HYW treatment downregulated the expression of Pik3ca, Akt1, Pdk1, and VEGFA, and inhibited the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, and VEGFA.</div></div><div><h3>Conclusion</h3><div>HYW effectively inhibits the malignant proliferation of NSCLC cells. The mechanism of its anti-cancer effects is likely mediated by the suppression of the PI3K/AKT/VEGFA signaling pathway. This finding provides new molecular insights into the potential therapeutic application of HYW in the treatment of lung cancer.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119724"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperacute intervention with DGMI for optimized stroke recovery: Modulating immune and inflammatory pathways in motor and sensory cortices","authors":"Zi-Yin Wu ,&nbsp;Zhi-Hong Guo ,&nbsp;Wen-Xin Lv ,&nbsp;Le Zhan,&nbsp;Xin-Yao Zhang,&nbsp;Yan Gao,&nbsp;Lei Wang,&nbsp;Jia-Yu Dong,&nbsp;Wen-Jing Dai,&nbsp;Liang Cao,&nbsp;Tuan-jie Wang,&nbsp;Zhen-Zhong Wang,&nbsp;Xin-Zhuang Zhang,&nbsp;Wei Xiao","doi":"10.1016/j.jep.2025.119734","DOIUrl":"10.1016/j.jep.2025.119734","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Long-term neurological dysfunction following stroke significantly impairs patients' quality of life. <em>Ginkgo biloba</em> L (GBL), a traditional Chinese herbal medicine, has shown promise in treating ischemic stroke and related disorders. Diterpene Ginkgolides Meglumine Injection (DGMI), derived from GBL, has demonstrated improved recovery outcomes in stroke patients when administered during the hyperacute phase (HAP) in clinical studies, yet the underlying mechanisms remain elusive.</div></div><div><h3>Materials and methods</h3><div>Utilizing a Transient Middle Cerebral Artery Occlusion (tMCAO) model, we evaluated the effects of DGMI at varying doses and administration times on neurological function, brain injury, and identified key genes/pathways via RNA-seq and bioinformatics analyses, validated by RT-PCR. An <em>in vitro</em> LPS-induced astrocyte activation model was used to evaluate DGMI's anti-inflammatory effects.</div></div><div><h3>Results</h3><div>DGMI administered during the hyperacute phase (HAP, 0.5 h post-tMCAO) exhibited superior neuroprotection compared to the acute phase (AP, 24 h post-tMCAO) in mice. HAP-DGMI significantly enhanced survival rates, reduced neurological deficit scores, infarct sizes, and neuronal apoptosis, with more pronounced improvements observed on days 3 and 7 post-tMCAO. Transcriptome sequencing revealed that HAP-DGMI more effectively normalized abnormal gene expression profiles, particularly in genes involved in immune and inflammatory pathways, in both motor (M1) and sensory (S1) cortices. Additionally, HAP-DGMI reversed a higher proportion of disease-characteristic pathways compared to AP.</div></div><div><h3>Conclusions</h3><div>These findings underscore the potential of early HAP intervention with DGMI in enhancing neuroprotection and functional recovery in AIS bymodulating key immune and inflammatory genes and pathways, providing experimental and theoretical support for the clinical application of DGMI.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119734"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic analysis and experiment to verify the mechanism of Xiaoyao San in the treatment of irritable bowel syndrome with depression","authors":"Jiaoyan Yu ,&nbsp;Xi Li ,&nbsp;Yantao Sun ,&nbsp;Ludan Wang ,&nbsp;Yajun Zhang","doi":"10.1016/j.jep.2025.119732","DOIUrl":"10.1016/j.jep.2025.119732","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Xiaoyao san (XYS) is a classic traditional Chinese medicine compound first recorded in \"Taiping Huimin Heji Ju Fang\". Traditionally, it is used to treat irritable bowel syndrome (IBS) and depression. However, its mechanism of action in treating IBS patients with depressive symptoms is still unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the effects of XYS on intestinal and depressive symptoms in IBS and explore the mechanisms through transcriptomic analysis and pharmacological experiments.</div></div><div><h3>Materials and methods</h3><div>IBS was induced in mice through a combination of chronic unpredictable mild stress and intragastric senna leaf stimulation. We evaluated six depressive parameters, examined colon tissue with hematoxylin and eosin staining and transmission electron microscopy, analyzed related proteins using western blotting, and performed transcriptomics on brain and intestinal tissues. The possible mechanism of action was speculated by network analysis of transcriptome results and further verified using the IBS model.</div></div><div><h3>Results</h3><div>The results show that XYS restored mouse weight, reduced intestinal symptoms and sensitivity, suppressed villous loss and atrophy, and enhanced the integrity of the intestinal mucosal barrier. Notably, XYS decreased the depression-like behavior. Transcriptomic analysis combined with pharmacological experiments revealed that XYS inhibited the expression of proteins related to the intestinal ACT1/TRAF6/P38MAPK/AP-1 signaling pathway while activating the brain's DRD2/TH signaling pathway and increasing dopamine release in the brain.</div></div><div><h3>Conclusions</h3><div>XYS may regulate the brain-gut axis function and improve intestinal and depressive symptoms in IBS model mice through the intestinal ACT1/TRAF6/P38MAPK/AP-1 signaling pathway and the brain DRD2/TH signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119732"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendrobium nobile lindl extract modulates integrin αIIbβ3-mediated signaling pathways to inhibit platelet activation and thrombosis","authors":"Chaoying Hua ,&nbsp;Meng Wu ,&nbsp;Yi Xiao ,&nbsp;Rui Zhang ,&nbsp;Yujing Yuan ,&nbsp;Li Zhang ,&nbsp;Fang Guo ,&nbsp;Jian Liu ,&nbsp;Zhanzhan Yang ,&nbsp;Gang Liu","doi":"10.1016/j.jep.2025.119728","DOIUrl":"10.1016/j.jep.2025.119728","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Dendrobium nobile</em> Lindl. (DNL) is a promising medicinal plant. It has the traditional medicinal effects of promoting blood circulation and resolving stasis, as well as regulating the meridians and collaterals.</div></div><div><h3>Aim of the study</h3><div>We studyed how DNL extract was involved in platelet activation and thrombosis and used network pharmacology and molecular docking analysis to help clarify the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The effect of DNL extract on platelet aggregation and ATP release function was examined by aggregometer; The effect of DNL extract on the binding of PAC-1 and fibrinogen to integrin was determined by flow cytometry; The effect of DNL extract on “outside-in” platelet signals was detected by platelet adhesion, spreading and clot retraction; Key compounds and major targets of platelet interactions with DNL extract were analyzed by network pharmacology and molecular docking and verified against related pathway proteins by western blotting; The effect of DNL extract on thrombosis was tested by mesenteric artery embolism model.</div></div><div><h3>Results</h3><div>DNL extract exhibited inhibition of platelet function and PAC-1 and fibrinogen binding to integrin αIIbβ3. In addition, it delayed FeCl₃-induced mesenteric artery thrombosis without affecting the clotting time and the hemostatic time of tail in mice. The detection of platelet “inside-out” and “outside-in” signaling by Western blot further confirmed the inhibitory effect of DNL extract on platelet activation.</div></div><div><h3>Conclusions</h3><div>DNL extract may affect the thrombosis process by inhibiting platelet activation via inhibiting integrin αⅡbβ3-mediated bidirectional signaling pathway proteins.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119728"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Hydroxyboesenbergin B of Alpinia japonica protected gastrointestinal tract by inhibiting vancomycin-resistant enterococcus and balancing intestinal microbiota","authors":"Li-Na Mei ,&nbsp;Zhao-Jie Wang ,&nbsp;Yu Duan ,&nbsp;Jia-Shan Shen ,&nbsp;Hong-Bo Ye ,&nbsp;Yan-Yan Zhu ,&nbsp;Xiao-Dong Luo","doi":"10.1016/j.jep.2025.119737","DOIUrl":"10.1016/j.jep.2025.119737","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Alpinia japonica</em>, a traditional herb utilized in Miao medicine in southwestern China, has been employed to alleviate symptoms such as stomachache, diarrhea, and abdominal pain, some of these symptoms may be associated with bacterial infections of the gastrointestinal tract.</div></div><div><h3>Aim of the study</h3><div>To explore antimicrobial compounds related to traditional uses of <em>A. japonica</em> and its potential pathway <em>in vitro</em> and <em>in vivo.</em></div></div><div><h3>Materials and methods</h3><div>Bioactive components of <em>A</em>. <em>japonica</em> were isolated by bioguide separation method. The antibacterial bioactivity of 4-hydroxyboesenbergin B (4-HB) was evaluated by time-kill curve and drug resistance induction. The pathway of 4-HB against VRE was investigated through network pharmacological analysis and validated by <em>in vitro</em> experiments and RT-qPCR assays. Moreover, a mouse gastrointestinal tract model was established to validate the antibacterial bioactivity of 4-HB <em>in vivo</em>.</div></div><div><h3>Results</h3><div>4-HB from <em>A</em>. <em>japonica</em> inhibited VRE (MIC = 16 μg/mL), rapidly killed the bacteria within 4 h at the 4 MIC concentration and exhibited low susceptibility to drug resistance. 4-HB specifically targeted VRE biofilms by down-regulating the expression of <em>AtlA</em>, <em>SgrA</em>, <em>GelE</em>, and <em>Ace</em>. As a result, 4-HB diminished the adhesion and aggregation ability of VRE, reduced the extracellular matrix content, disrupted biofilm structure and morphology, thereby reducing VRE resistance and virulence. Additionally, 4-HB significantly reduced VRE colonization, enhanced intestinal microbiota diversity, and promoted the restoration of intestinal microbiota balance in <em>vivo</em>. Notably, 4-HB enhanced the abundance of beneficial bacteria genera, such as <em>Lactobacillus</em> and <em>Limosilactobacillus</em>.</div></div><div><h3>Conclusions</h3><div>4-HB has a significant ability to destroy VRE biofilms and balance intestinal microbiota, which might be responsible for the traditional use of <em>A. japonica</em> partly.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119737"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huaier enhances the antitumor effects of CDK 4/6 inhibitor by remodeling the immune microenvironment and gut microbiota in breast cancer","authors":"Yifei Wang ,&nbsp;Xiaolong Wang ,&nbsp;Wenhao Li ,&nbsp;Hanwen Huang ,&nbsp;Chenyu Di ,&nbsp;Qifeng Yang","doi":"10.1016/j.jep.2025.119723","DOIUrl":"10.1016/j.jep.2025.119723","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Trametes robiniophila Murr</em> (Huaier), a traditional Chinese medicine (TCM), has shown promising effects as a complementary therapy in the treatment of multiple kinds of cancers.</div></div><div><h3><em>Aim of the study</em></h3><div>This study aimed to systematically evaluate whether Huaier could enhance the antitumor effects of palbociclib, a highly selective CDK4/6 inhibitor.</div></div><div><h3>Materials and methods</h3><div>A breast cancer xenograft mouse model was constructed to assess the anticancer effects of Huaier and palbociclib. Transcriptomic analysis was performed to identify the differentially expressed genes and associated pathways. Flow cytometry, immunofluorescence and immunohistochemical staining were then conducted to observe the infiltration of immune cells in the tumor microenvironment (TME). The composition of the gut microbiota was explored through 16S rDNA sequencing, and a pseudosterile mouse model was established to verify the contribution of the gut microbiota to the antitumor effects of Huaier and palbociclib.</div></div><div><h3>Results</h3><div>Oral administration of Huaier enhanced the antitumor effects of palbociclib in breast cancer. Transcriptomic analysis of tumor tissues revealed that the differentially expressed genes were related to immune functions. Indeed, the addition of Huaier to palbociclib therapy further increased the ratio of CD8⁺/CD3⁺ T cells and the abundance of GzmB⁺CD8⁺ T cells in the TME. Mechanistically, sequencing of 16S rDNA revealed that Huaier reshaped the gut microbiota composition in favor of <em>Akkermansia</em>, which positively modulated antitumor immune responses. The pseudosterile mouse model verified the necessity of the gut microbiota for the synergistic effect of Huaier on palbociclib. Furthermore, butyrate, a metabolite of <em>Akkermansia</em>, synergized with palbociclib to suppress tumor progression and promote the infiltration of CD8⁺ T cells in the TME.</div></div><div><h3>Conclusions</h3><div>Our data suggested that Huaier augmented the antitumor effects of palbociclib by increasing the abundance of <em>Akkermansia</em> in gut microbiota, which contributed to the enhancement of anti-tumor immunity. Consequently, combining palbociclib with Huaier may serve as a promising strategy for the treatment of breast cancer.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"347 ","pages":"Article 119723"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}