Combinatorial chemistry & high throughput screening最新文献

{"title":"Guanxinkang Decoction and Its Key Component Isotanshinone II Ameliorate Atherosclerosis Through Modulation of STAT3/ CD36 Signaling and Macrophage Efferocytosis: An Integrated Network Pharmacology and Experimental Validation Study.","authors":"Shuaijie Guo, Chen Gao, Hong Shen, Haixin Kou, Shuo Yang, Zhenyue Fu, Yifan Zhang, Yiru Wang, Ping Liu, Jing Wei","doi":"10.2174/0113862073490408260805053210","DOIUrl":"https://doi.org/10.2174/0113862073490408260805053210","url":null,"abstract":"<p><strong>Introduction: </strong>To investigate the potential anti-atherosclerotic mechanisms of Guanxinkang (GXK), with emphasis on its association with STAT3/CD36 pathway regulation and efferocytosis-related signaling.</p><p><strong>Methods: </strong>Network pharmacology identified key targets, which were validated by molecular docking and dynamics simulations. ApoE-/- mice and ox-LDL-induced foam cell models established in RAW264.7 macrophages were employed. GXK was administered at 7.22 and 14.43 g/kg/day in vivo and 0.5 and 2 mg/mL in vitro. In vivo and in vitro experiments assessed lipid profiles, plaque formation, inflammatory cytokines, and macrophage efferocytosis.</p><p><strong>Results: </strong>GXK at both low (7.22 g/kg, GXK-L) and high doses (14.43 g/kg with higher concentration, GXK-H) significantly improved serum lipid profiles (reduced TC, TG, LDL-C; increased HDL-C; P<0.05), reduced atherosclerotic plaque area, and suppressed pro-inflammatory cytokines IL-1β and IL-6 while upregulating IL-10 (P<0.05). Mechanistically, GXK significantly inhibited CD36 expression and reduced STAT3 phosphorylation (P<0.01) and modulated efferocytosis- related proteins TIM-4 (upregulated) and CD47 (downregulated) (P<0.05), suggesting enhanced macrophage efferocytosis capacity. Isotanshinone II, a key GXK component, exhibited similar effects in vitro, alleviating lipid accumulation and modulating CD36, STAT3, and efferocytosis-related proteins.</p><p><strong>Discussion: </strong>These results suggest that the therapeutic efficacy of GXK in atherosclerosis is attributed to its multi-target regulatory capacity. By suppressing the STAT3/CD36 axis, GXK not only restricts lipid influx but also restores the homeostatic clearance of apoptotic cells through enhanced efferocytosis.</p><p><strong>Conclusions: </strong>GXK may exert anti-atherosclerotic effects that are associated with modulation of the STAT3/CD36 axis and efferocytosis-related signaling; however, causal validation requires further investigation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention or Treatment of Dengue Virus Disease: An Update on Recent Vaccination and Therapeutics Globally.","authors":"Rajendra Kumar, Sampada Pendse, Jitendra Kumar, Rashi Shukla, Surendra Mehra, Saurabh Singh, Shubham Chaudhary, Ankit Sahu, Rituraj Niranjan","doi":"10.2174/0113862073471606260806033008","DOIUrl":"https://doi.org/10.2174/0113862073471606260806033008","url":null,"abstract":"<p><p>Dengue fever is one of the most serious public health issues in tropical and subtropical regions, transmitted by the mosquito Aedes. There are four serotypes of the Dengue virus [DENV, types 1-4]. Every year, millions of people contract dengue infection. Symptoms range from fever to the more complicated condition of hemorrhagic fever. Vector control remains an important tool for preventing dengue, but no antiviral drugs are available to date. Recent progress in prevention has been achieved through vaccine development with licensed vaccines such as Dengvaxia and TAK-003. Both are demonstrating varying degrees of efficacy, and many concerns related to safety and reduced effectiveness in seronegative or dengueuninfected individuals remain unresolved. In parallel, several RNA-based vaccines and antiviral agents are currently under investigation and may provide hope for improved and broader protection against DENV in the future. On the other hand, therapeutic approaches such as antiviral peptides, monoclonal antibodies, nanotechnology-based interventions, and compounds targeting viral replication have shown positive outcomes in preclinical and early clinical trials. Nevertheless, the presence of four serotypes and the complex immunopathology of DENV infection continue to complicate both vaccine and therapeutic development. Technological progress has significantly advanced dengue control by developing rapid diagnostic technologies and using data to predict disease outbreaks. A holistic approach encompassing vaccination, targeted therapeutics, vector control, diagnostic innovation, and global cooperation is imperative for mitigating the global threat of dengue. Although vaccines are indispensable for disease prevention, new treatment options are essential for directly managing dengue infections.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Physiological, Biochemical, and Pathological Characteristics of Adenine-Induced Kidney-Yang Deficiency in Rats.","authors":"Rong-Rui Wei, Qing-Yuan Lin, Zhao Geng, Qin-Ge Ma, Wen-Min Liu, Guo-Yue Zhong, Qing-Gang Zhou, Xu-Tao Wu","doi":"10.2174/0113862073478002260806105646","DOIUrl":"https://doi.org/10.2174/0113862073478002260806105646","url":null,"abstract":"<p><strong>Introduction: </strong>Kidney-Yang deficiency is a syndrome crucial for understanding the function of traditional Chinese medicine (TCM) in kidney diseases. The model enables us to explore the applications of TCM for treating Kidney-Yang deficiency and provide practical guidance for TCM.</p><p><strong>Methods: </strong>The rats were orally administered medication continuously for 21 days. The thymus, spleen, gland, testis, and epididymis were collected, and organ indices were calculated. The pathological sections of the kidney, spleen, and testis were prepared to observe morphological changes.</p><p><strong>Results: </strong>This study established a validated, reproducible biomarker framework linking adenineinduced renal injury to Kidney-Yang deficiency. High-dose adenine persistently disrupted the hypothalamic-pituitary-target gland axes and suppresses IL-2-mediated immune function, with causal mechanistic links rather than parallel descriptions. The T4, ACTH, GnRH, LH, and FSH gradually approached normal levels after one week. The high-dose adenine group significantly reduced serum IL-2 levels. Medium- and high-dose adenine induced notable kidney, spleen, and testicular pathological changes in rats. These integrated markers provided a scientifically reproducible bridge for defining Kidney-Yang deficiency with modern biomedical endpoints.</p><p><strong>Discussion: </strong>The Kidney-Yang deficiency model was established by inducing kidney injury in SD rats with adenine. The kidney injury was closely related to Kidney-Yang deficiency syndrome. The Kidney-Yang deficiency model is crucial for studying drug metabolism in the treatment of the syndrome.</p><p><strong>Conclusions: </strong>The low-, medium-, and high-dose adenine-induced Kidney-Yang deficiency models in SD rats impact liver/kidney function and immune indicators. Different adenine doses and modeling times affect biochemical indicators and the severity of Kidney-Yang deficiency to varying degrees.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDFA-MLP: Multi-scale Dilated Fusion Attention and Ensemble Framework for Anticancer Peptide Prediction.","authors":"Binyu Li, Zhihua Huang, Yijie Ding, Xiaoyi Guo","doi":"10.2174/0113862073468655260630193344","DOIUrl":"https://doi.org/10.2174/0113862073468655260630193344","url":null,"abstract":"<p><strong>Introduction: </strong>Experimental identification of anticancer peptides (ACPs) is timeconsuming and costly, which limits large-scale ACP discovery and screening. To address this challenge, we developed MDFA-MLP, a novel computational framework for ACP prediction that integrates multi-scale feature learning and ensemble classification strategies.</p><p><strong>Methods: </strong>The proposed framework combines physicochemical descriptors, including amino acid composition (AAC), dipeptide composition (DPC), composition-transition-distribution (CTD), and pseudo-amino acid composition (PseAAC), with ProtBERT-derived embeddings. A Multiscale Dilated Fusion Attention (MDFA) module was designed to capture sequence patterns at different scales and enhance feature fusion. An ensemble classifier consisting of a multilayer perceptron (MLP), support vector machine (SVM), and histogram-based gradient boosting (HGB) was employed to improve prediction robustness and stability.</p><p><strong>Results: </strong>The proposed model was evaluated on the AntiCP 2.0 dataset under the different negative-sample settings. On Dataset A, MDFA-MLP achieved an accuracy of 93.9%, sensitivity of 92.2%, specificity of 95.8%, and an MCC of 0.89. On the more challenging Dataset B, the model achieved an accuracy of 78.2%, sensitivity of 76.5%, specificity of 82.6%, and an MCC of 0.65. Comparative experiments demonstrated that MDFA-MLP achieved competitive and balanced performance across multiple evaluation metrics. Although the improvement over existing methods was moderate in some cases, the model maintained stable predictive performance under different negative-sample settings, indicating good robustness and generalization ability.</p><p><strong>Discussion: </strong>The results indicate that traditional sequence descriptors and deep protein language model embeddings provide complementary biological information. The MDFA module effectively enhances feature representation by integrating multi-scale sequence characteristics, while the ensemble strategy improves model robustness and generalization under varying data distributions.</p><p><strong>Conclusion: </strong>MDFA-MLP provides an effective and reliable framework for ACP prediction. By integrating handcrafted descriptors, protein language model representations, and ensemble learning, the proposed method can facilitate large-scale computational screening of candidate ACPs prior to experimental validation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physicochemical Characterization and Biological Activity of Ethanol- Extracted Residue of Saussurea involucrata.","authors":"He Cui, Qi Li, Yanna Yao, Xinyu Wang, Shuge Tian","doi":"10.2174/0113862073470898260602093207","DOIUrl":"https://doi.org/10.2174/0113862073470898260602093207","url":null,"abstract":"<p><strong>Introduction: </strong>Saussurea involucrata's ethanol-extracted residue (ROSI), a byproduct of its oral liquid preparation, nevertheless holds significant therapeutic promise. To evaluate its potential as a treatment for neurodegenerative illnesses, this study investigates its physicochemical properties and biological activity.</p><p><strong>Materials and methods: </strong>UV-Vis, IR spectroscopy, UHPLC-Q Exactive HFX systems, microscopy, powder characterisation, and thermogravimetric analysis were used to examine the physical and chemical characteristics of ROSI. Antioxidant activities and pancreatic lipase inhibition were assessed. Its therapeutic targets for neurodegenerative disorders were predicted by network pharmacology and molecular docking analyses.</p><p><strong>Results: </strong>ROSI demonstrated high organic acid content, a uniform porous structure, consistent particle size, and high thermal stability, meeting industrial flowability standards. While showing modest pancreatic lipase inhibition, it exhibited potent antioxidant activity. Pharmacomics analysis suggests ROSI may target multiple pathways involved in neurodegenerative diseases.</p><p><strong>Discussion: </strong>Despite its modest pancreatic lipase inhibitory effect, ROSI exhibits potent antioxidant activity and stable physicochemical properties suitable for industrial applications. Network pharmacology and molecular docking analyses reveal therapeutic potential for ROSI in neurodegenerative diseases such as Alzheimer's and Parkinson's. Consequently, ROSI serves as a natural antioxidant and a raw material for the development of functional foods and pharmaceuticals.</p><p><strong>Conclusion: </strong>ROSI holds promise as an adjunctive treatment for neurodegenerative diseases, particularly for its antioxidant effects and industrial applicability. Further research should optimize its use in chronic disease management and explore its broader medicinal potential.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th17 Cell-Related Gene Biomarkers in Autoimmune Thyroiditis: Comprehensive Bioinformatics Analysis and In Vivo Validation.","authors":"Ziyu Liu, Ming Ren, Jiayun Li, Zhuo Zhao, Hao Gao, Guanghan Wang, Ying Zhang","doi":"10.2174/0113862073420296251128070854","DOIUrl":"https://doi.org/10.2174/0113862073420296251128070854","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this research was to comprehensively explore the molecular pathways through which Th17 cells contribute to autoimmune thyroiditis (AIT). This was achieved by pinpointing key gene biomarkers associated with Th17 cell activity and elucidating their regulatory functions in thyroid inflammation.</p><p><strong>Methods: </strong>High-throughput sequencing data of thyroid tissues from AIT patients and controls were obtained from the GEO database. The transcriptomic analysis was performed to quantify immune cell infiltration using ImmunCellAI, with a particular focus on Th17 cells. Candidate genes were identified through differential expression analysis between the groups, with criteria of |log2FC| > 1 and p.adj < 0.05. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape to identify hub genes. The core genes were validated in an independent dataset (GSE29315) and further tested in a NOD.H-2h4 mouse model. The diagnostic efficacy of the identified genes was assessed using ROC curve analysis.</p><p><strong>Results: </strong>In patients with autoimmune thyroiditis (AIT), the proportion of Th17 cells was significantly elevated, along with increased expression of genes associated with Th17 cells. Through transcriptomic analysis, a total of 235 upregulated and 128 downregulated differentially expressed genes (DEGs) were identified. Protein-protein interaction (PPI) network analysis highlighted 10 hub genes, including TLR2, TROAP, AURKB, and TK1, which were correlated with Th17 cell infiltration. These genes demonstrated high diagnostic accuracy, with area under the curve (AUC) values ranging from 0.85 to 1.00. Additionally, these genes were found to be upregulated in the thyroid tissues of AIT mouse models and correlated with inflammation and antibody levels.</p><p><strong>Discussion: </strong>This study identified Th17-related biomarkers (TLR2, TROAP, AURKB, TK1) in autoimmune thyroiditis (AIT), offering new molecular targets for targeted therapies. Future research is needed to elucidate cell-type-specific mechanisms underlying AIT pathogenesis using in vitro and in vivo models, thereby advancing personalized treatment strategies.</p><p><strong>Conclusion: </strong>Th17-related genes TLR2, TROAP, AURKB, and TK1 serve as high-performance diagnostic biomarkers for autoimmune thyroiditis and offer novel molecular targets for precision therapy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mini-review on the Chemical Constituents and Biological Activities of Selliguea Bory.","authors":"Wenbin Zhang, Honglong Ding, Zejin Xie, Yuxi Chen, Dianchu Li, Jianping Yong","doi":"10.2174/0113862073464394260730055041","DOIUrl":"https://doi.org/10.2174/0113862073464394260730055041","url":null,"abstract":"<p><p>The genus Selliguea Bory represents one kind of fern with significant pharmacological potential and is rich in diverse bioactive compounds, including flavonoids, phenylpropanoids, terpenoids, and steroids, which make it exhibit a broad spectrum of biological activities, such as antioxidant, antidiabetic, antimicrobial, antifibrotic, anticancer, and postmenopausal osteoporosis- alleviating effects. However, the chemical constituents and biological activities of Selliguea Bory are yet to be systematically reviewed. Therefore, this review comprehensively summarizes the progress made over the past decade in the chemical components (50 reported compounds) and the biological activities of Selliguea Bory, providing a systematic scientific basis and highlighting future research directions for the further development of this genus.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic Fermentation Improves Shenzhi Decoction's Hepatoprotection via Gut-Liver Axis Modulation: A Multi-Omics Study on Acute Liver Injury.","authors":"Jing Wang, Xiaolei Tang, Lin Li, Zhuang Xiong, Jianmin Liu, Guangyu Cheng","doi":"10.2174/0113862073463143260727091908","DOIUrl":"https://doi.org/10.2174/0113862073463143260727091908","url":null,"abstract":"<p><strong>Introduction: </strong>Traditional Chinese Medicine (TCM), with its multi-target action and holistic regulatory mechanism, offers a promising alternative to modern health management. Shenzhi Decoction (SZD) is a case in point. It originated in the long-term application of TCM in liver health. In recent years, to enhance the bioavailability and biological activity of its components, researchers have further co-fermented SZD with specific probiotics to develop Shenzhi Jiaosu (SZJS). SZJS showed a better hepatoprotective effect than SZD, but its efficacy was unknown. This study aims to compare the protective effects of SZD and SZJS in a CCl4-induced acute liver injury model and to examine their potential mechanisms of action.</p><p><strong>Materials and methods: </strong>SZD uses a combination of probiotics for fermentation, including patented strains Lactobacillus plantarum (RZKLp100), Lactobacillus casei (ZKLc1221), and Lactobacillus acidophilus (RZKLa0701). TOF-MS was used to detect the chemical composition of SZD and SZJS. CCL4 was used to construct a mouse model for acute liver injury, and SZD or SZJS were given to treat the injury. Liver injury and oxidative stress were evaluated by measuring serum ALT/AST levels, antioxidant enzyme activities, and histopathological examination. Bulk RNA sequencing, network pharmacology, and molecular docking were employed to identify potential mechanisms and targets. HE staining and IHC were used to assess gut barrier integrity, and 16S rRNA sequencing was used to assess gut microbial diversity.</p><p><strong>Results: </strong>Probiotic fermentation significantly altered the chemical profile of SZD, enriching bioactive metabolites such as L-methionine and biochanin A derivatives. SZJS demonstrated superior efficacy compared with SZD in alleviating liver damage, reducing ALT/AST levels, restoring antioxidant enzyme activity, and reversing pathological changes. Transcriptome analysis revealed enhanced regulation of immune and metabolic pathways, while network pharmacology and molecular docking identified EGFR, PTGS2, and TLR9 as key molecular targets. Furthermore, SZJS improved gut barrier integrity and microbiota composition, enriching beneficial genera and microbial functions involved in detoxification and redox homeostasis.</p><p><strong>Discussion: </strong>These findings suggest that probiotic fermentation enhances the hepatoprotective activity of SZD by reshaping its chemical composition and promoting coordinated regulation of the gut-liver axis, inflammation, oxidative stress, and metabolic homeostasis.</p><p><strong>Conclusion: </strong>Probiotic fermentation can significantly enhance the liver-protecting efficacy of SZD by reshaping the chemical substance basis. By integrating multi-omics results, the synergistic mechanism may be related to the regulation of the \"gut-liver axis\".</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Danggui Shaoyao Powder in the Treatment of Ulcerative Colitis: A Network Pharmacology Approach with Experimental Validation.","authors":"Yanxia Huang, QiaoHong Lin, Min Zhu, Ke Chen, Xuehua Cai, Aizhen Pan, Bin Zhang","doi":"10.2174/0113862073461624260724044224","DOIUrl":"https://doi.org/10.2174/0113862073461624260724044224","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Danggui Shaoyao Powder (DSP), a classical prescription in Traditional Chinese Medicine (TCM), has garnered growing evidence for its promising therapeutic effects on ulcerative colitis (UC). Nevertheless, the specific molecular mechanisms responsible for its anti-UC activity remain poorly understood. Herein, we integrated network pharmacology with experimental validation to systematically explore and clarify the underlying mechanisms of DSP in the treatment of UC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Network pharmacology was utilized to identify the active components and therapeutic targets of DSP in the treatment of UC. Subsequently, a protein-protein interaction (PPI) network of the identified targets was constructed using the STRING database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to evaluate the binding affinity between the primary bioactive components of DSP and Th17-associated proteins. Finally, the protective efficacy of DSP in maintaining immune homeostasis and alleviating inflammation was validated in vivo using a dextran sulfate sodium (DSS)- induced UC mouse model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 51 active components of DSP and 103 corresponding targets were retrieved from the TCMSP database. Additionally, 4,419 potential targets associated with UC were identified from the OMIM, DisGeNET, and GeneCards databases. Sixty-three overlapping potential targets were identified as therapeutic targets of DSP against UC, which were subsequently refined to construct an optimized protein-protein interaction network containing 100 central nodes. Key hubs included IL-6, AKT1, ESR1, CASP3, PTGS2, BCL2, PPARG, HSP90AA1, TGF-β1, and JUN, and these targets were highly enriched in pathways associated with inflammatory regulation and immune signaling, with Th17 cell differentiation serving as a key biological process. Molecular docking demonstrated stable binding affinities between the DSP components Paeoniflorin and Stigmasterol and the core targets TGF-β1 and IL-6 (binding energy &lt; -5 kcal/mol). Furthermore, in vivo experiments demonstrated that DSP ameliorated symptoms and histological changes in DSS-induced colitis by inhibiting Th17 cell differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This study provides experimental evidence supporting the protective effects of DSP against UC, with its actions likely mediated, at least in part, through the modulation of Th17 cell differentiation. These results deepen our insight into the mechanistic underpinnings of DSP activity and can serve as a theoretical basis for the further advancement of DSP-based therapeutic strategies for UC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;DSP has shown potential as a therapeutic agent for UC by acting on multiple core targets and relevant signaling pathways, with the modulation of Th17 cell differentiation serving as a key mediating mechani","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tongnao Decoction Facilitates Angiogenesis via the VEGFA/ PI3K/AKT/JUNB Signaling Axis to Promote Stroke Recovery.","authors":"Wanhui Peng, Fei Ma, Yan Liu, Ziyan Cai, Yongxing Deng, Shufan Xu, Zhaoyao Chen, Qinghua Feng, Liqin Luan, Wenlei Li, Yuan Zhu, Minghua Wu","doi":"10.2174/0113862073467840260609152218","DOIUrl":"https://doi.org/10.2174/0113862073467840260609152218","url":null,"abstract":"<p><strong>Introduction: </strong>Acute ischemic stroke (AIS) is a leading cause of global disability and mortality, with treatments limited by narrow time windows. Tongnao Decoction (TND), a traditional Chinese medicine formula, has shown neuroprotective potential. This study investigates TND's mechanism in promoting post-stroke recovery.</p><p><strong>Methods: </strong>Chemical analysis of TND using UHPLC-QTOF-MS identified 20 bioactive compounds. A photothrombosis-induced mouse stroke model was established and confirmed by TTC staining and MRI.</p><p><strong>Results: </strong>Behavioral tests showed TND significantly improved motor function, an effect reduced by the VEGFR2 inhibitor SKLB1002.</p><p><strong>Discussion: </strong>In human cerebral microvascular endothelial cells (HCMECs), TND (1375 μg/mL) enhanced viability by 53.3%, proliferation by 1.5-fold, migration by 73%, and tube formation by 1.3-fold. Western blot analysis revealed that TND upregulates p-PI3K/PI3K, p-AKT/AKT, and JUNB, which was reversed by SKLB1002.</p><p><strong>Conclusion: </strong>In conclusion, TND facilitates functional recovery after AIS by promoting angiogenesis via the VEGFA/PI3K/AKT/JUNB pathway, supporting its therapeutic potential for ischemic stroke.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}