PhytomedicinePub Date : 2025-06-08DOI: 10.1016/j.phymed.2025.156958
Xin Su , Wanyu Yang , Zhiqiang Yan , Zhihua Hao , Jing Jin , Yanyu Liu , Siqi Wu , Yutong He
{"title":"Targeting tumor metabolism: The dual attack of emodin on glycolysis and oxidative phosphorylation in esophageal squamous cell carcinoma","authors":"Xin Su , Wanyu Yang , Zhiqiang Yan , Zhihua Hao , Jing Jin , Yanyu Liu , Siqi Wu , Yutong He","doi":"10.1016/j.phymed.2025.156958","DOIUrl":"10.1016/j.phymed.2025.156958","url":null,"abstract":"<div><h3>Background</h3><div>Esophageal squamous cell carcinoma (ESCC) exhibits elevated death rate and varying resistance to multiple chemotherapeutic agents. Emodin, a key constituent of rhubarb, has demonstrated anticancer activities in colorectal and breast cancers. However, its application and mechanism in ESCC await full clarification.</div></div><div><h3>Purpose</h3><div>This study investigates emodin's inhibitory impacts on ESCC <em>in vitro</em> and <em>in vivo</em> and explores its underlying molecular mechanisms, with the aim of identifying a potential candidate for ESCC treatment.</div></div><div><h3>Methods</h3><div>To explore the mechanisms by which emodin acts in ESCC, network pharmacology, bioinformatics analysis, proteomic profiling, and Seahorse assays were employed to assess alterations in cellular energy metabolism. The expression extent of the end result markers and pathway proteins induced by emodin were assessed using Western blotting. To evaluate the potential toxicity and antitumor efficacy of emodin in ESCC, a xenograft tumor model was utilized <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Emodin inhibited ESCC cell proliferation, facilitated intrinsic apoptosis, and induced G2/M phase arrest. Proteomic analysis results showed that emodin disrupted cellular energy metabolism by inhibiting both mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. Network pharmacology and rescue experiments identified the p53 and FOXO signaling pathways as key mediators of these effects. <em>In vivo</em> xenograft experiments further supported the inhibitory activity of emodin in ESCC.</div></div><div><h3>Conclusion</h3><div>Emodin induces intrinsic apoptosis in ESCC cells by simultaneously inhibiting both glycolysis and OXPHOS. These results support emodin's potential as a candidate therapeutic candidate for ESCC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156958"},"PeriodicalIF":6.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263068","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":"Multi-omics characterization of prognostic signature and novel molecular subtypes associated with anoikis and in vitro validation of CDKN2A in thyroid carcinoma","authors":"Kaigang Xie, Xiaoming Hong, Xiaoting Ren, Zhenjun Tong","doi":"10.1016/j.phymed.2025.156956","DOIUrl":"10.1016/j.phymed.2025.156956","url":null,"abstract":"<div><h3>Background</h3><div>Anoikis plays a crucial role in thyroid carcinoma (THCA). Recent evidence has suggested CDKN2A as a key anoikis-related gene (ARG) associated with THCA. However, the multi-omics regulatory landscape of ARGs and their potential to define molecular subtypes with distinct therapeutic vulnerabilities remain unexplored.</div></div><div><h3>Methods</h3><div>We utilized multi-omics data from The Cancer Genome Atlas including transcriptomic, methylation, and miRNA profiles, to analyze ARG expression and survival outcomes in THCA patients. Single-cell sequencing and clustering analyses were conducted to identify distinct molecular subtypes. A risk scoring model was developed based on ARGs, and its predictive performance was validated. Drug vulnerability was assessed to determine the sensitivity of molecular subtypes to various therapies.</div></div><div><h3>Results</h3><div>Patients with THCA demonstrated a pronounced shift toward positive anoikis regulation compared with healthy controls. Integrated multi-omics analyses identified E2F1, LGALS3, CDKN2A, and LPAR1 as key prognostic genes. A risk score model incorporating these genes exhibited strong predictive accuracy, with a C-index of 0.85. Unsupervised clustering delineated two distinct molecular subtypes—Cluster 1 and Cluster 2—with Cluster 1 associated with enhanced inflammatory cell infiltration and superior overall survival. Drug sensitivity profiling further revealed differential responses to conventional chemotherapies and targeted therapies between the two subtypes. Functional validation established CDKN2A as a critical mediator of anoikis resistance and immune microenvironment modulation in THCA.</div></div><div><h3>Conclusions</h3><div>This study advances prior research by establishing the first multi-omics-driven molecular subtypes of THCA, and provides a comprehensive regulatory framework for anoikis in THCA. The identification of subtype-specific drug vulnerabilities and functional validation of CDKN2A's role in stromal crosstalk offer transformative insights for personalized therapy.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156956"},"PeriodicalIF":6.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298632","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}
PhytomedicinePub Date : 2025-06-07DOI: 10.1016/j.phymed.2025.156928
Minsong Guo , Zhengqin Wang , Xiaogang Zhou , Chonglin Yu , Jianming Wu , Lu Yu , Jianing Mi , Fang Ren , Betty Yuen Kwan Law , Hudan Pan , Vincent Kam Wai Wong , Dalian Qin , Anguo Wu
{"title":"Ciliatoside A attenuates neuroinflammation in Alzheimer's disease by activating mitophagy and inhibiting NLRP3 inflammasome activation","authors":"Minsong Guo , Zhengqin Wang , Xiaogang Zhou , Chonglin Yu , Jianming Wu , Lu Yu , Jianing Mi , Fang Ren , Betty Yuen Kwan Law , Hudan Pan , Vincent Kam Wai Wong , Dalian Qin , Anguo Wu","doi":"10.1016/j.phymed.2025.156928","DOIUrl":"10.1016/j.phymed.2025.156928","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a gradually worsening neurological condition that involves memory loss, brain inflammation, and impaired mitochondrial function. The NLRP3 inflammasome activation in microglia plays a pivotal role in promoting neuroinflammation and worsening disease progression. Mitochondrial dysfunction and impaired mitophagy further create a detrimental feedback loop of oxidative stress and inflammation. Despite extensive research, pharmacological agents capable of simultaneously targeting both NLRP3 inflammasome activation and impaired mitophagy remain scarce.</div></div><div><h3>Methods</h3><div>We explored the therapeutic potential of Ciliatoside A (CA), a novel natural compound isolated from <em>Peristrophe japonica</em>, utilizing comprehensive cellular and animal models. In lipopolysaccharide/nigericin (LPS/Nig)-stimulated BV-2 microglial cells, the impact of CA on inflammasome activation, pyroptosis, mitochondrial health, and oxidative stress was assessed. Mechanistic evaluations were conducted using Western blotting, immunofluorescence, and advanced mitophagy assays. Furthermore, the efficacy of CA was validated in <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) models expressing human amyloid-beta (Aβ) and the well-established 3xTg-AD mouse model.</div></div><div><h3>Results</h3><div>Our results demonstrate CA effectively inhibits NLRP3 inflammasome activation, reduces microglial pyroptosis, and mitigates oxidative stress-induced mitochondrial impairment in BV-2 cells. Notably, we identified the AMPK/ULK1 and PINK1/Parkin pathways as novel targets through which CA robustly activates mitophagy. Consistent therapeutic effects were observed in vivo, with CA significantly reducing Aβ-induced paralysis, ROS generation, and enhancing autophagy in worms. In 3xTg-AD mice, CA markedly improved cognitive function, diminished Aβ plaque deposition, alleviated neuroinflammation, and preserved neuronal integrity.</div></div><div><h3>Conclusion</h3><div>For the first time, this study reveals that CA offers dual neuroprotective benefits by promoting mitophagy while inhibiting NLRP3 inflammasome-mediated neuroinflammation. These novel insights highlight the innovative therapeutic potential of CA, suggesting its promising application in slowing AD progression and mitigating its pathological features.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156928"},"PeriodicalIF":6.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313060","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}
PhytomedicinePub Date : 2025-06-07DOI: 10.1016/j.phymed.2025.156923
Rui Li , Qi Lou , Yu Zhu , Min Si , Xiaoyu Zhu , Huiyu Jia , Haoran Yang , Tingting Ji , Dongrui Xu , Wulin Yang , Shengyong Luo , Yijun Wang
{"title":"Mechanism of Huoshan large-leaf yellow tea in treatment of diabetic cognitive dysfunction based on bioinformatics and network pharmacology","authors":"Rui Li , Qi Lou , Yu Zhu , Min Si , Xiaoyu Zhu , Huiyu Jia , Haoran Yang , Tingting Ji , Dongrui Xu , Wulin Yang , Shengyong Luo , Yijun Wang","doi":"10.1016/j.phymed.2025.156923","DOIUrl":"10.1016/j.phymed.2025.156923","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic cognitive dysfunction (DCD) is a prevalent complication of diabetes, characterized by progressive cognitive decline. Current pharmacological interventions have limited therapeutic efficacy in managing this condition. Huoshan large - leaf yellow tea (HLYT), derived from Camellia sinensis leaves, has demonstrated dual pharmacological properties in both glycemic regulation and cognitive enhancement, suggesting its potential as a preventive and therapeutic agent for DCD.</div></div><div><h3>Purpose</h3><div>The main purpose of this study was to clarify the regulatory effect of HLYT on DCD and explore its underlying mechanisms.</div></div><div><h3>Study design</h3><div>The research encompassed a comprehensive multi-phase investigation. Network pharmacological analysis identified HLYT's key target genes for DCD. Molecular docking screened hub target genes, which were further verified by molecular dynamic (MD) simulations. High-performance liquid chromatography (HPLC) quantified HLYT's active components for setting animal experiment dosages. A DCD model was established in rats by feeding them a high - fat diet and injecting streptozotocin (STZ). Subsequently, HLYT was administered to the rats via intragastric gavage for intervention. The results of this intervention were then verified through relevant animal experiments.</div></div><div><h3>Results</h3><div>Utilizing an integrated approach of network pharmacology and molecular docking, five pivotal target genes (Adora2a, Mapk8, Stat3, Vcam1, Edn1) were identified as the primary molecular targets of HLYT in DCD pathogenesis. Quercetin, kaempferol, caffeine, theobromine, and EGCG in HLYT exhibited significant binding affinities with these targets. The results of animal experiment have shown that HLYT can alleviate neuronal damage and cognitive dysfunction, reduce the levels of IL-6 and IL-1β in the serum and brain tissue in DCD rats. Furthermore, it can also inhibit the expression of Adora2a, Mapk8, Stat3, Vcam1, and Edn1 mRNA as well as the expression of STAT3, ADORA2A, JNK1, ET1, and VCAM1 proteins.</div></div><div><h3>Conclusion</h3><div>HLYT has a significant protective effect on DCD in rats by regulating Adora2a, Mapk8, Stat3, Vcam1, and Edn1 genes, suggesting that it has remarkable clinical potential in the treatment of DCD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156923"},"PeriodicalIF":6.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253938","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}
PhytomedicinePub Date : 2025-06-06DOI: 10.1016/j.phymed.2025.156949
Qijing Wang , Xuhui Yuan , Hongyan Li , Jiayu Li , Zhaoyang Wu , Wenming Zhang , Xinyu Fang
{"title":"Guggulsterone suppresses osteosarcoma progression by inhibiting glycolysis through MAPK signaling pathway","authors":"Qijing Wang , Xuhui Yuan , Hongyan Li , Jiayu Li , Zhaoyang Wu , Wenming Zhang , Xinyu Fang","doi":"10.1016/j.phymed.2025.156949","DOIUrl":"10.1016/j.phymed.2025.156949","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) represents an aggressive primary cancer originating in bone. It is predominantly diagnosed in pediatric and young adult populations, constituting approximately 20 % of bone malignancies in these age groups. Treatment efficacy is often hampered by chemoresistance. Guggulsterone (GS), a plant-derived sterol from Commiphora wightii, demonstrates promising anti-tumor potential, yet its effects on OS remain unexplored.</div></div><div><h3>Purpose</h3><div>The objective of this research was to clarify the anti-cancer mechanisms through which GS acts in OS and to evaluate its therapeutic prospects, with a particular focus on its influence over glycolysis and related signaling pathways.</div></div><div><h3>Methods</h3><div>In vitro investigations involved assessing cell viability, colony formation capability, apoptosis via flow cytometry, migration using Transwell assays, and protein levels by Western blot. Transcriptomic changes were evaluated using RNA sequencing. The anti-tumor efficacy of GS in vivo was confirmed using xenograft tumor models.</div></div><div><h3>Results</h3><div>GS treatment led to a significant decrease in OS cell proliferation, induced cell cycle arrest at the G2/M phase, and promoted apoptosis. Furthermore, GS suppressed OS cell migration and invasion, concurrent with modulation of proteins related to epithelial-mesenchymal transition (EMT). Mechanistically, GS targeted the MAPK signaling pathway, which resulted in impaired glycolytic activity and altered cellular energy metabolism. In vivo, administration of GS curtailed tumor growth without inducing noticeable systemic toxicity.</div></div><div><h3>Conclusion</h3><div>GS effectively counteracts OS progression by inhibiting glycolysis through MAPK pathway suppression. These findings suggest GS represents a promising therapeutic avenue for OS treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156949"},"PeriodicalIF":6.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279186","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}
PhytomedicinePub Date : 2025-06-06DOI: 10.1016/j.phymed.2025.156486
Abudureyimu Alimujiang , Yutong Kang , Wenjing Wei , Zehua Zhang , Yipeng Bai , Yong Zhu , Shixia Huo , Dengqiu Xu , Zhijian Li
{"title":"Apigenin suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting CDK2/E2F2 pathway","authors":"Abudureyimu Alimujiang , Yutong Kang , Wenjing Wei , Zehua Zhang , Yipeng Bai , Yong Zhu , Shixia Huo , Dengqiu Xu , Zhijian Li","doi":"10.1016/j.phymed.2025.156486","DOIUrl":"10.1016/j.phymed.2025.156486","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a long-lasting inflammatory skin condition marked by unusual growth of keratinocytes and infiltration of immune cells in the dermis and epidermis. Dijincao (DJC), a key component of Qing Xue Wan (QXW), is traditionally used to treat psoriasis. Although its clinical efficacy is well-recognized, the absence of pharmacological and mechanistic studies limits the validation of DJC as an effective and scientifically substantiated treatment for psoriasis.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-psoriasis activity of QXW and DJC, identify their most effective constituents, and elucidate the underlying mechanisms of action.</div></div><div><h3>Methods</h3><div>Mice with imiquimod (IMQ)-induced psoriasis were treated with QXW or DJC, and the therapeutic effects were evaluated using the Psoriasis Area and Severity Index (PASI), histological analysis, immunohistochemistry, immunofluorescence, RT-PCR, and ELISA. Additionally, UPLC-QTOF/MS technology and lipopolysaccharide (LPS)-induced human keratinocytes (HaCaT) cells were employed to identify the main active components of DJC. Mechanistic insights were gained through RNA sequencing, Western blotting, cell cycle analysis, and luciferase assays.</div></div><div><h3>Results</h3><div>Treatment with QXW and DJC resulted in a significant reduction of the PASI score, skin thickness, spleen index, and inflammatory cell infiltration. Moreover, both QXW and DJC reduced serum levels of pro-inflammatory cytokines. DJC alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response. UPLC-QTOF/MS analysis and LPS-induced HaCaT cell studies identified Apigenin as the principal active compound of DJC. Transcriptomic analysis, along with WB, cell cycle, and luciferase assays, revealed that Apigenin mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the CDK2/E2F2-mediated cell cycle and IL-17 signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study represents the first comprehensive comparison of the anti-psoriatic effects of QXW, DJC, and Apigenin. The findings suggest that the therapeutic effects of QXW and DJC are primarily attributed to Apigenin, which exerts anti-proliferative properties by inhibiting the CDK2/E2F2 signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156486"},"PeriodicalIF":6.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279185","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}
PhytomedicinePub Date : 2025-06-06DOI: 10.1016/j.phymed.2025.156944
Yu Cao , Kexuan Zhao , Yudi Zhao , Ying Ni , Zicheng Zhang , Xinyi Yuan , Jiamei Ning , Qinghua Song , Fan Zhao , Ling He , Tong Chen
{"title":"Arbutin ameliorated depression by inhibiting neuroinflammation and modulating intestinal flora","authors":"Yu Cao , Kexuan Zhao , Yudi Zhao , Ying Ni , Zicheng Zhang , Xinyi Yuan , Jiamei Ning , Qinghua Song , Fan Zhao , Ling He , Tong Chen","doi":"10.1016/j.phymed.2025.156944","DOIUrl":"10.1016/j.phymed.2025.156944","url":null,"abstract":"<div><h3>Background</h3><div>Arbutin (AR), a natural glycoside compound widely distributed in botanical sources, exerts neuroprotective properties. Nevertheless, the pharmacological effect of AR on depression and its underlying mechanism remain undefined.</div></div><div><h3>Methods</h3><div>The mice were induced by chronic unpredictable mild stress (CUMS) procedure 16S rRNA sequencing and metabolomic analyses were conducted. The <em>in vitro</em> neuroinflammatory model was established using lipopolysaccharide (LPS) stimulated BV2 microglia.</div></div><div><h3>Results</h3><div>The present study found that AR alleviated the depressive-like behaviors, inflammatory reaction, oxidative stress, restored neurotrophic factors and gut tight junction proteins. TLR4/NF-κB/IRAK1 signaling was involved in these alterations. 16S rRNA sequencing and metabolomics showed that AR enriched <em>muribaculaceae</em> and tryptophan metabolism. <em>Muribaculum intestinale</em> and AR ameliorated depressive-like behaviors, inflammation and 5-HT content, Tryptophan Hydroxylase 1 (TPH1) and Indoleamine 2,3-Dioxygenase 1 (IDO1) expressions, tryptophan metabolism and kynurenine route. The molecular docking and molecular dynamic suggested that AR might bind to TPH1 and IDO1.</div></div><div><h3>Conclusion</h3><div>In conclusion, AR alleviated depressive-like behavior in mice by reducing neuroinflammation, modulating gut microbiota, and TPH1/IDO1-mediated serotonin synthesis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156944"},"PeriodicalIF":6.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313058","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}
PhytomedicinePub Date : 2025-06-06DOI: 10.1016/j.phymed.2025.156915
Yongyan Chen , Xu Han , Yuxuan Hao , Xu Wang , Fupeng Wu , Sheng Tan , Huijing Ye , Yang Hong , Xiaoyan Shen
{"title":"Emodin-induced ERα degradation via SYVN1 alleviates vascular calcification by preventing HIF-1α deacetylation in chronic kidney disease","authors":"Yongyan Chen , Xu Han , Yuxuan Hao , Xu Wang , Fupeng Wu , Sheng Tan , Huijing Ye , Yang Hong , Xiaoyan Shen","doi":"10.1016/j.phymed.2025.156915","DOIUrl":"10.1016/j.phymed.2025.156915","url":null,"abstract":"<div><h3>Background</h3><div>Vascular calcification is a major cause of death in chronic kidney disease (CKD), with osteoblastic transdifferentiation of vascular smooth muscle cells (VSMCs) considered to be the crucial pathologic process. However, there remains a significant deficiency in effective prevention and treatment strategies.</div></div><div><h3>Purpose</h3><div>In an in vitro calcification screening model, we observed an inhibitory activity of Emodin on osteoblastic transdifferentiation of VSMCs. In the present study, we therefore aimed to evaluate its efficacy in CKD-induced medial vascular calcification in vitro and in vivo, and to further explore the underlying mechanisms.</div></div><div><h3>Study design</h3><div>A7R5 and MOVAS cells were treated with sodium phosphate to induce osteogenic transdifferentiation as in vitro models, while mice were fed with adenine and a high-phosphorus diet, and additionally received an intraperitoneal injection of 10,000 IU Vitamin D3 to induce chronic kidney disease (CKD) as an in vivo model. Vitamin K2 served as a positive control.</div></div><div><h3>Methods</h3><div>Alizarin Red S staining and VON-KOSSA staining were used to evaluate the effects of Emodin on osteogenic transdifferentiation. Western blotting, RT-qPCR and Von-Kossa staining were used to detect the effects of Emodin on aortic calcification in CKD mice in vivo. Chemical biology techniques including ITC, fluorescence titration, dual fluorescein reporter genes, CETSA, and DARTS, were used to detect the binding activity of Emodin to ERα and SYVN1. Immunoprecipitation, immunostaining, etc. were used to explore the mechanisms, and small molecule inhibitors and small RNA interference were used to verify the target of Emodin.</div></div><div><h3>Results</h3><div>Emodin could effectively inhibit the osteogenic transdifferentiation of A7R5 and MOVAS cells in vitro, and alleviate aortic calcification in CKD mice in vivo. Mechanism study revealed that Emodin could act as a molecular glue that binds directly to ERα and SYVN1 and enhances their interaction, thereby accelerating the ubiquitination degradation process of ERα. The decrease in ERα diminished the inhibition of ERα on the deacetylation of HIF-1α by SIRT6, thereby inhibiting VSMC osteogenic transdifferentiation and relieving the vascular cells calcification.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that ERα has a non-genomic effect to inhibit the deacetylation of HIF-1α by SIRT6, which can be abrogated by Emodin through SYVN1-mediated ERα degradation. These results provide evidences for Emodin to serve as a candidate drug for controlling clinical vascular calcification in CKD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156915"},"PeriodicalIF":6.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313059","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}
PhytomedicinePub Date : 2025-06-06DOI: 10.1016/j.phymed.2025.156903
Jiansheng Li , Hailong Zhang , Huanrong Ruan , Guixiang Zhao , Hailang He , Congxia Hou , Weixu Sun , Shuaihui Hou , Xiaozhuang Liu , Ya Li
{"title":"Efficacy and safety of Chinese medicine in treating risk window of AECOPD: A multicenter randomized controlled trial","authors":"Jiansheng Li , Hailong Zhang , Huanrong Ruan , Guixiang Zhao , Hailang He , Congxia Hou , Weixu Sun , Shuaihui Hou , Xiaozhuang Liu , Ya Li","doi":"10.1016/j.phymed.2025.156903","DOIUrl":"10.1016/j.phymed.2025.156903","url":null,"abstract":"<div><h3>Background</h3><div>Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) significantly accelerate disease progression and substantially increase mortality risk. The risk window of AECOPD (AECOPDRW) represents a time between acute exacerbation and recovery to a stable stage. Chinese medicine (CM) has shown significant therapeutic efficacy in COPD but CM treatment for AECOPDRW has not been validated by high-quality clinical studies.</div></div><div><h3>Purpose</h3><div>To assess the clinical effect of CM syndrome differentiation treatment for patients with AECOPDRW.</div></div><div><h3>Study design</h3><div>A multicenter, randomized, double-blind, placebo-controlled parallel trial.</div></div><div><h3>Methods</h3><div>336 eligible participants were included to the study. Both groups were based on the conventional treatment as the baseline therapy. The experimental group was administered Chinese herbal medicine granules based on CM syndrome differentiation, whereas the control group received a placebo in the form of Chinese herbal medicine granules. The intervention course lasted for 8-week, while the follow-up for 26-week. Primary outcomes were incidences of acute exacerbation and COPD Assessment Test (CAT) scores recorded during AECOPDRW. Secondary outcomes were the timing of the first acute exacerbation, incidence of exacerbations, acute exacerbation readmission rate, severity of exacerbation, and CAT scores during follow-up, pulmonary function, mMRC scale, clinical symptom scale, and the quality of life assessment tools.</div></div><div><h3>Results</h3><div>At 8-week, the risk of acute exacerbations and CAT score were significantly reduced in the experimental group between-group analysis with a risk ratio (RR) of 0.375(95 % confidence interval [CI]: 0.150 to 0.935; <em>p</em> = 0.027), and a mean difference (MD) of -2.476 score (95 % CI: -3.281 to -1.671; <em>p</em> < 0.001). At 26-week, experimental group showed statistically lower risk of acute exacerbation between-group analysis (RR: 0.519; 95 % CI: 0.282 to 0.953; <em>p</em> = 0.030). The first exacerbation time in the experimental group (97.63 ± 35.90) was statistically longer than in the control group (66.11 ± 25.25) (MD: 31.517 (95 % CI: 14.720 to 48.314; <em>p</em> < 0.001). The rates of acute exacerbation readmission were similar for both the groups during the risk window and follow-up period. After 26 weeks of follow-up, experimental group CAT score was reduced by 2.046 between-group analysis <em>(p</em> < 0.001). Furthermore, during the whole study, the experimental group showed significantly reduced in mMRC score, as well as FEV<sub>1</sub> and FVC values (all <em>p</em> < 0.05). During study period, the experimental group had a significant reduce in clinical symptom scores, including cough, expectoration, and fatigue, than the control group (<em>p</em> < 0.05). Regarding to SGRQ, mCOPD-PRO and mESQ-COPD, our results demonstrated that CM had b","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156903"},"PeriodicalIF":6.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270291","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}
PhytomedicinePub Date : 2025-06-05DOI: 10.1016/j.phymed.2025.156935
Wei Hu , Chen Li , Chenguang Wang , Wei Liu , Chuntong Li , Lihua Mu , Kun Wang , Mengli Chen
{"title":"Exploring the therapeutic mechanism of Miao nationality medicine Qijiao Shengbai capsule on leukopenia based on multi-omics, network pharmacology and experimental verification","authors":"Wei Hu , Chen Li , Chenguang Wang , Wei Liu , Chuntong Li , Lihua Mu , Kun Wang , Mengli Chen","doi":"10.1016/j.phymed.2025.156935","DOIUrl":"10.1016/j.phymed.2025.156935","url":null,"abstract":"<div><h3>Introduction</h3><div>Leukopenia is caused by numerous factors, and modern drug therapies have obvious side effects, Qijiao Shengbai Capsule (QJSB) is a compound prescription developed from Miao medicine, widely used in clinical treatment of leukopenia. However, its mechanism of action for treating leukopenia remains unclear.</div></div><div><h3>Objectives</h3><div>This study aims to investigate the active ingredients, effects and underlying mechanism of QJSB on leukopenia.</div></div><div><h3>Materials and methods</h3><div>In this study, the chemical components of QJSB and serum constituents were identified using UPLC-Q-Qrbitrap HRMS technology. The potential anti-leukopenia mechanism and crucial components of QJSB was deciphered using combined approaches of transcriptomic analysis and network pharmacology analysis. Finally, the expression of key targets and the intervene effects of QJSB in the cyclophosphamide-induced leukopenia model of rats was verified by in vivo experiments.</div></div><div><h3>Results</h3><div>In total, 51 and 58 chemical components were identified from QJSB and serum respectively. The network pharmacology analysis indicated that the key components of QJSB was genistein, quercetin, 5,6,7-trimethoxyisoflavone, carbacyclin, linoleic acid, and caffeic acid, the key targets were PTPN11, LCK, STAT3, GRB2, FYN, SRC, PIK3R1, LYN, EGFR, PIK3CA, and the key pathways were PI3K-Akt, lipid and atherosclerosis, JAK-STAT, FoxO, and linoleic acid metabolism. Transcriptomics analysis revealed that 1171 genes were down-regulated and 382 genes were up-regulated by QJSB compared with model group. KEGG pathway enrichment analysis indicated that the PI3K-AKT signaling pathway is closely related to leukopenia. Animal experiments demonstrated that QJSB and its active components effectively increased serum levels of hematopoietic and immune-related cytokines, improved thymus index, spleen index, and bone marrow nucleated cell count in model rats through regulating PI3K-AKT signaling pathway and downstream transcription factors mTOR and FOXO3A.</div></div><div><h3>Conclusion</h3><div>Our research demonstrated for the first time that genistein, quercetin, and caffeic acid is the key active components of QJSB and this miao nationality medicine can treat leukopenia through regulating the PI3K-AKT-mTOR/FoxO3a signaling axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156935"},"PeriodicalIF":6.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263065","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}