Combinatorial chemistry & high throughput screening最新文献

{"title":"HuangE Capsules Improve Bladder Function in BOO-induced Overactive Bladder Rats: Network Pharmacology and Experimental Validation.","authors":"Peizhe Li, Yuewen Pang, Shiyu Zhao, Heyang Liu, Siyu Han, Ran Zhong, Shuang He, Jing Shi, Haisheng Cheng, Yongji Yan, Junyao Duan, Huijie Gong","doi":"10.2174/0113862073373430250415070358","DOIUrl":"https://doi.org/10.2174/0113862073373430250415070358","url":null,"abstract":"<p><strong>Aims: </strong>Our objective is to assess the therapeutic impact of HEC on OAB rats and investigate potential mechanisms.</p><p><strong>Background: </strong>Overactive bladder (OAB) is a syndrome of urinary storage symptoms characterized by \"urinary urgency with or without urinary acute incontinence, usually accompanied by increased daytime and nocturnal urination\", which impacts patients' quality of life. We found the potential therapeutic impact of HuangE capsules (HEC) on OAB patients through clinical practice. However, the exact effect and mechanism of action remain unclear.</p><p><strong>Methods: </strong>We developed a \"drugs- active ingredients- targets- diseases\" network and employed the pathway enrichment analysis to identify the potential mechanisms of HEC on OAB. Bladder outlet obstruction (BOO) models and sham-operated ones were established in healthy male Wistar rats through surgical procedures. Following 28 days of continuous gavage administration of HEC, saturated copper sulfate test paper was utilized to quantify the frequency of urination over a 24- hour period. Subsequently, cystostomy was conducted to perform cystometry, and Masson staining was applied to a portion of the bladder tissue. Finally, we investigated the Rho/Rho-kinase pathway's expression and assessed the oxidative stress and inflammatory factor levels in the rat bladder through western blotting and ELISA techniques.</p><p><strong>Results: </strong>Through network pharmacological analysis, we identified RhoA/Rho-kinase pathway and cytokine including TNF-α, IL-6, SOD and MDA as potential mechanisms of HEC on OAB. The rats in the 2× HuangE group exhibited significantly enhanced urodynamic outcomes and decreased 24-hour urination frequency compared to the model group. Masson staining indicated a decrease in the proportion of collagenous tissue and an improvement in histomorphology. We observed a decrease expression of RhoA, ROCK1, and ROCK2 protein in the bladder tissue of 2× HuangE group rats, along with elevated SOD levels and decreased levels of TNF-α, IL-6, and MDA.</p><p><strong>Conclusion: </strong>HEC could improve bladder function and morphology in BOO-induced OAB rats by reducing the expression of RhoA, ROCK1, and ROCK2 and lowering levels of oxidative stress and inflammation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966841","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":"Shenhuang Liuwei Powder Alleviates Streptozotocin-Induced Diabetic Ulcers in Rats through the Inhibition of the AGE/RAGE Signaling Pathway and Promotion of Antibacterial Activity and Angiogenesis via Activation of the PI3K/Akt/eNOS/HIF-1α Pathway.","authors":"Jun Li, Qian Zhang, Shengnan Li, Shu Wang, Fengye Zhou, Haifeng Zhang, Jianping Chen","doi":"10.2174/0113862073370028250326071104","DOIUrl":"https://doi.org/10.2174/0113862073370028250326071104","url":null,"abstract":"<p><strong>Aims and objective: </strong>Shenhuang Liuwei powder (SHLWP) is frequently used to treat diabetic ulcers (DUs), but its mechanism of action remains poorly understood. This study aimed to identify the active compounds and mechanisms by which SHLWP alleviates DUs.</p><p><strong>Methods: </strong>The chemical components of SHLWP were analyzed using high-resolution mass spectrometry (HRMS). Network pharmacology based on HRMS data identified SHLWP-associated targets and signaling pathways. Its antibacterial activity was assessed using Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC) tests. Its in vivo pharmacological effects were evaluated in a streptozotocin-induced diabetic ulcer model in Sprague-Dawley (SD) rats.</p><p><strong>Results: </strong>Seventy-three components were identified in SHLWP, with key constituents including caffeic acid (13.11 ± 0.14 μg/g), ferulic acid (20.40 ± 0.24 μg/g), quercetin (8.49 ± 0.18 μg/g), luteolin (36.63 ± 0.19 μg/g), apigenin (82.14 ± 1.60 μg/g), and linoleic acid (507.59 ± 1.46 μg/g). SHLWP exhibited strong antibacterial activity against Staphylococcus aureus (MIC = 7.8125 μg/mL), Streptococcus pyogenes (MIC < 3.90625 μg/mL), and Streptococcus epidermidis (MIC < 3.90625 μg/mL). Network pharmacology revealed significant enrichment of the AGE/RAGE, HIF-1, and PI3K-Akt pathways, which was validated in vivo using qPCR, immunohistochemistry, and Western blot.</p><p><strong>Conclusion: </strong>SHLWP alleviated streptozotocin-induced diabetic ulcers by inhibiting the AGE/RAGE pathway and promoting antibacterial activity and angiogenesis via the PI3K/Akt/eNOS/HIF-1α pathway, providing a biological basis for its therapeutic effects.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968329","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":"Eco-friendly Advancements through Fish Waste: A Review of Therapeutic and Industrial Innovations.","authors":"Saddam Hussain, Aminur Rahman, Pranab Borah, Arlin Sen, Raju Bharalee, Mayuri Chabukdhara, Hrishikesh Upadhyaya, Akalesh Kumar Verma","doi":"10.2174/0113862073372954250408181058","DOIUrl":"https://doi.org/10.2174/0113862073372954250408181058","url":null,"abstract":"<p><p>Fish waste, a significant by-product of the fisheries industry, presents both an environmental challenge and a valuable resource. This review delves into the innovative approaches to harness the potential of fish waste for various applications, particularly in the biomedical and industrial sectors. Therapeutically, fish waste yields valuable bioactive compounds such as omega-3 fatty acids, collagen peptides, and gelatine, which are known to benefit cardiovascular, skin, and immune health. Fish-derived collagen, for instance, is employed in wound healing, bone regeneration, and cosmetic applications due to its biocompatibility and lower infection risk compared to land-animal sources. Omega-3 fatty acids from fish waste exhibit anti-inflammatory, anticancer adding value to pharmaceutical industries. Industrially, fish waste can be transformed into eco-friendly materials like bioplastics, biofuels, and biofertilizers, contributing to environmental sustainability. Bioplastics synthesized from fish scales and biotextiles developed from collagen-modified polyester exemplify sustainable alternatives to synthetic materials. Additionally, fish-based biofertilizers enhance soil fertility, promoting greener agriculture. Innovations also include the production of fish-based leather, low-cost fish peptones for microbial culture, and fish oil-based biofuel with diesel-like properties, showcasing versatile applications. This review explores the untapped potential of fish waste, emphasizing its underutilized yet high-value therapeutic and industrial applications. Unlike existing studies, it focuses on lesser-explored areas such as fish-derived biofertilizers for precision agriculture and fish-based bioplastics for sustainable packaging. These applications can significantly reduce pollution, promote non-toxic alternatives, and contribute to sustainable industries. By leveraging fish waste, this review aims to address environmental challenges, support global health initiatives, and highlight innovative solutions for a circular economy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969440","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":"Qishen Huoxue Granule Ameliorates LPS-induced Cardiomyocyte Injury by Suppressing Excessive Autophagy via MasR/PI3K-AKT-mTOR Pathway.","authors":"Yu-Fan Du, Zheng Wang, Huan Tang, Zhao-Qing Lu, Guo-Xing Wang","doi":"10.2174/0113862073359792250401180222","DOIUrl":"https://doi.org/10.2174/0113862073359792250401180222","url":null,"abstract":"<p><strong>Objective: </strong>Qishen Huoxue Granule (QHG), a classical Traditional Chinese Medicine prescription, can reduce septic cardiomyopathy in the clinic. However, the mechanism of QHG remains unclear. This study aims to investigate the mechanism and effect of QHG-contained serum (QHG-CS) on sepsis-induced cardiomyopathy (SICM).</p><p><strong>Methods: </strong>QHG was administered to Wistar rats via gavage to obtain QHG-CS. The chemical constituents of QHG-CS were identified via UPLC-Q-TOF-MS. In vitro, rat cardiomyocytes H9c2 cells isolated from embryonic BD1X rat heart tissue, and septic myocardial injury model was established by inducing H9c2 cells with lipopolysaccharide (LPS). Cell viability was assessed through CCK-8. Protein expression was determined using western blot, and gene expression was measured using real-time quantitative PCR. Cell autophagy was investigated by detecting LC3 expression using flow cytometry and immunofluorescence. In addition, three inhibitors, A779 (MasR), wortmannin (PI3K) and rapamycin (mTOR) were used to focus the potential therapeutic targets.</p><p><strong>Results: </strong>QHG-CS significantly improved the survival of septic cardiomyocytes (p<0.0001). The expression of autophagy-related markers Beclin1, ATG5, and LC3II/I was increased in LPSinduced cardiomyocytes, which could be inhibited by QHG-CS. QHG-CS upregulated the mRNA expression of MasR, PI3K, and AKT, as well as the phosphorylation of PI3K, AKT, and mTOR. Moreover, A779 markedly lowered mRNA levels of MasR, PI3K, and mTOR, while wortmannin decreased mRNA levels of PI3K and mTOR, whereas rapamycin only suppressed mTOR phosphorylation.</p><p><strong>Conclusions: </strong>By inhibiting excessive autophagy through upregulation of the MasR/PI3K-AKTmTOR pathway, QHG can alleviate sepsis-induced cardiomyocyte damage. This study provides novel perspectives for the management of sepsis-induced cardiac damage.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957436","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":"MiR-26a-5p/EZH2 Mediates Wnt2 Promoter Methylation to Regulate Trophoblast Dysfunction.","authors":"Xiaoyu Zhou, Shiqi Wei, Ning Yu, Yufang Liu","doi":"10.2174/0113862073360368250404104831","DOIUrl":"https://doi.org/10.2174/0113862073360368250404104831","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is a common complication of pregnancy, with a concomitant incidence rate of up to 10% among pregnant women worldwide.</p><p><strong>Methods: </strong>In the current research, we explored the role and mechanism of miR-26a-5p in trophoblast function using CCK-8, colony formation assay, and flow cytometry. The interaction between miR-26a-5p and EZH2 was analyzed using a luciferase reporter assay. Methylationspecific PCR was performed to detect the methylation level of Wnt2 in HTR8 cells.</p><p><strong>Results: </strong>Wnt2 and miR-26a-5p promoted the proliferation and inhibited the apoptosis in trophoblasts (P<0.05). The secretion of inflammatory cytokines was suppressed by Wnt2 and miR-26a- 5p (P<0.05). EZH2 was identified as a regulatory target of miR-26a-5p using HTR8 cells and bioinformatic tools. miR-26a-5p inhibited expression through direct binding to EZH2. Importantly, miR-26a-5p mediated DNA methylation of Wnt2 to regulate Wnt2 expression in HTR8 cells.</p><p><strong>Conclusion: </strong>It was found that miR-26a-5p increased the expression of Wnt2 by downregulating EZH2. Moreover, miR-26a-5p/EZH2/Wnt2 promoted the proliferation and inhibited the inflammation and apoptosis in trophoblasts. This research provides insight into the role of miR-26a- 5p/EZH2/Wnt2 as a novel indicator for the prevention and treatment of PE.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971720","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 Mechanism of Ranunculus ternatus Thunb. against Esophageal Squamous Cell Carcinoma Based on Network Pharmacology and Experimental Verification.","authors":"Michen Deng, Yanhong Deng, Zugui Tang, Wenqiang Nie, Yi Lu, Xicheng Wang, Zhe Wang, Yi Kong","doi":"10.2174/0113862073376779250410054456","DOIUrl":"https://doi.org/10.2174/0113862073376779250410054456","url":null,"abstract":"<p><strong>Background: </strong>Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health challenge, underscoring the urgent need for the development of innovative therapeutic approaches. Ranunculus ternatus Thunb., a traditional herbal medicine, has shown potential anticancer properties, but its pharmacological mechanisms against ESCC remain poorly understood. This study aimed to elucidate the molecular mechanisms of the ethyl acetate extract of Ranunculus ternatus Thunb. (RTE) against ESCC by integrating network pharmacology analysis with experimental validation.</p><p><strong>Methods: </strong>Potential targets of RTE and ESCC were identified through network pharmacology using public databases. A Protein-Protein Interaction (PPI) network was constructed to identify key targets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore biological processes and signaling pathways. The predicted mechanisms were experimentally validated using in vitro assays, including cell proliferation analysis and western blot assay in ESCC cell lines.</p><p><strong>Results: </strong>Network pharmacology analysis identified 274 potential targets, with 14 key genes implicated in the therapeutic effects of RTE. GO analysis revealed significant involvement in the inflammatory response and apoptotic signaling pathways. KEGG pathway analysis highlighted the MAPK, Relaxin, and PI3K/Akt signaling pathways as critical mechanisms. In vitro experiments demonstrated that RTE significantly inhibited the proliferation of EC-109 and TE-13 cells by modulating the MAPK/ERK and PI3K/Akt pathways.</p><p><strong>Conclusion: </strong>This study provides a comprehensive understanding of the molecular mechanisms underlying the anticancer effects of RTE against ESCC. These findings underscore the potential of RTE as a promising natural compound for ESCC treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986885","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":"Exploring the Comorbidity Mechanism among Functional Diarrhea, Irritable Bowel Syndrome with Predominant Diarrhea, and Functional Dyspepsia through the Gut-brain Axis and the Pharmacological Mechanisms of Shen-Ling-Bai-Zhu-San Therapy.","authors":"Chunfeng Mei, Lili Han, Hong Xue","doi":"10.2174/0113862073329698250102120037","DOIUrl":"https://doi.org/10.2174/0113862073329698250102120037","url":null,"abstract":"<p><strong>Background: </strong>Functional Diarrhea (FDr), Irritable Bowel Syndrome with predominant diarrhea (IBS-D), and Functional Dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) with significant impacts on quality of life. While the gut-brain axis and key regulators like 5-hydroxytryptamine (5-HT), dopamine (DA), and butyrate are known to play crucial roles in these conditions, the mechanisms underlying their comorbidities remain unclear. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional herbal formula, is effective in treating FGIDs. Still, the specific components and mechanisms mediating its therapeutic effects via the gut-brain axis are not well understood.</p><p><strong>Methods: </strong>This study identified molecular links among FDr, IBS-D, and FD from the gut-brain axis using integrated biological information. The pharmacological mechanisms of SLBZS were explored through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro bio-layer interferometry (BLI) validation.</p><p><strong>Results: </strong>A total of 328 common targets were identified among FDr, IBS-D, and FD, with 22 hub genes in the protein-protein interaction (PPI) network associated with 5-HT/DA/butyrate pathways. Virtual screening revealed seven key targets (AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2, and IL1B) and 14 bioactive components (e.g., diosgenin and luteolin) from SLBZS. Molecular docking indicated strong binding affinities between key components and targets, while molecular dynamics simulations confirmed stable interactions, particularly between PTGS2 and diosgenin/luteolin. BLI experiments further validated the strong binding affinity of PTGS2 for diosgenin.</p><p><strong>Conclusion: </strong>This study elucidates potential targets shared by FDr, IBS-D, and FD through the gut-brain axis, highlighting diosgenin's interaction with PTGS2 as a potential mechanism of SLBZS's therapeutic effects. These findings provide valuable insights into the pharmacological mechanisms of SLBZS in treating FGIDs and suggest new avenues for targeted therapies.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964880","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":"Identification of the Role of Necroptosis-Related Genes in the Oxidative Damage of Lens Epithelial Cells and Validation in Ultraviolet B-induced Cataract in Rats.","authors":"Yongshun Liang, Qingqiao Gan, Xin Zhong, Tian Lan, Yingqin Yang, Hao Liang","doi":"10.2174/0113862073365864250312043532","DOIUrl":"https://doi.org/10.2174/0113862073365864250312043532","url":null,"abstract":"<p><strong>Introduction: </strong>The specific role of necroptosis in the pathogenesis of cataracts remains unclear. This study aimed to identify and validate the genes related to necroptosis in the development of cataracts through bioinformatics analysis.</p><p><strong>Method: </strong>We utilized RNA sequencing data (GSE161701) from the Gene Expression Omnibus (GEO) database and employed R software to perform differential expression analysis of necroptosis- related genes (NRGs) in lens epithelial cells (LECs) under oxidative stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to evaluate the functions of necroptosis-related differentially expressed genes (NRDEGs) and their associated pathways. Additionally, a diagnostic model was established using LASSO regression to select hub genes, and protein-protein interaction (PPI) networks, mRNA-miRNA, and mRNAdrug regulatory networks were constructed. Immune infiltration analysis was performed using the xCell and CIBERSORT algorithms, and the differential expression of hub genes was validated in a UVB-induced rat cataract model using RT-qPCR and immunohistochemistry.</p><p><strong>Results: </strong>The results indicated that oxidative stress promoted necroptosis in LECs, involving 86 NRDEGs and nine hub genes. GO and KEGG analyses revealed significant enrichment in necroptosis- associated pathways. Furthermore, we identified 58 mRNA-miRNA interactions and 131 potential molecular compounds or drugs. The immune infiltration analysis showed that certain immune cells exhibited significantly elevated expression in the cataract group, with notable correlations between some immune cells and hub genes. RT-qPCR and immunohistochemistry confirmed the expression of 9 hub genes and 3 key necroptosis genes. BAX, CXCL1, EPAS1, JUN, LRP1, RBM14, SERTAD1, and TNFAIP3 were highlighted as potential diagnostic and therapeutic targets.</p><p><strong>Conclusion: </strong>This study identified key NRDEGs involved in the pathogenesis of cataracts under oxidative stress through bioinformatics analyses, potentially providing new targets and research directions for future cataract prevention and treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981906","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":"Fuzi-Baijiangcao Herb Pair Alleviates DSS-induced Ulcerative Colitis in Mice via Inhibiting the p38 MAPK/NF-κB/HIF-1α Signaling Pathway.","authors":"Chengxin Sun, Yinghao Jiang, Xiaoyan Wang","doi":"10.2174/0113862073342236250103112654","DOIUrl":"https://doi.org/10.2174/0113862073342236250103112654","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis is an inflammatory intestinal tract disease that is complex and, difficult to heal, and prone to recurrence. The Fuzi-Baijiangcao (FB) herb pair is a commonly used drug combination for the clinical treatment of UC in China. However, its underlying mechanisms have not been elucidated. In this study, we explored the active ingredients of the FB herb pair and its potential mechanisms in the treatment of UC.</p><p><strong>Methods: </strong>Firstly, the active ingredients and potential targets of Aconitum carmichaelii Debeaux (Fuzi) and Patrinia villosa (Thunb.) Juss (Baijiangcao) were obtained through network pharmacology. We identified differentially expressed genes (DEGs) in UC by bioinformatics analysis. Then, the common targets of the FB herb pair and UC were obtained, and the protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R language. The potential mechanism of the herb pair was validated through DSS induced UC mouse model.</p><p><strong>Results: </strong>Thirty-four active ingredients corresponding to 546 potential targets were screened in the FB herb pair. Bioinformatics analysis revealed 2125 DEGs in UC. The GO and KEGG enrichment analyses showed that the FB herb pair was able to exert therapeutic effects by modulating multiple inflammatory pathways, including MAPK, HIF-1, and TNF. The results of animal experiments demonstrated that the FB herb pair could significantly downregulate the gene and protein expression of key molecules in the p38 MAPK/NF-κB/HIF-1α signaling pathway, thereby reducing the expression of pro-inflammatory factors and cell adhesion molecules, significantly improving the symptoms and intestinal pathology, and repairing the damage of the intestinal mucosa in the UC mice.</p><p><strong>Conclusions: </strong>FB herb pair has Apparent therapeutic effects on UC, and its mechanisms may be related to the regulation of the p38 MAPK/NF-κB/HIF-1α signaling pathway to reduce the expression of inflammatory factors and repair intestinal mucosal damage.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982775","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":"Xuebijing Alleviates Microglial Activation after Traumatic Brain Injury via Regulation of NF-κB Pathway: Network Pharmacology and Experimental Validation.","authors":"Hongran Fu, Xiaoyu Wang, Xuelin Mo, Jingwei Li, Dongkai Guo","doi":"10.2174/0113862073364997250324231219","DOIUrl":"https://doi.org/10.2174/0113862073364997250324231219","url":null,"abstract":"<p><strong>Objective: </strong>Xuebijing (XBJ) injection, a traditional Chinese medicine (TCM) widely used in China for treating sepsis and multiple organ dysfunction, has shown neuroprotective effects in traumatic brain injury (TBI). However, the mechanisms underlying these effects remain unclear. This study aims to elucidate the neuroprotective and pharmacological molecular mechanisms of XBJ and its active monomer, Hydroxy-safflor yellow A (HSYA), in treating TBI through network pharmacology and experimental validation.</p><p><strong>Methods: </strong>Potential therapeutic targets for TBI were collected from TCMSP, TTD, OMIM, and GeneCards databases. Active compounds and targets of XBJ injection were obtained from TCMSP. The STRING database and Cytoscape software constructed a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database and visualized with Bioinformatics tools. Neuroprotective effects of XBJ were verified in vitro using BV2 and primary microglia cells stimulated by Lipopolysaccharide (LPS). Additionally, a TBI mice model was used to identify microglial activation in vivo.</p><p><strong>Results: </strong>A total of 161 common targets related to TBI were identified. Network pharmacological analysis suggested that XBJ targets proteins involved in inflammation. In vitro results showed that XBJ and HSYA inhibited LPS-induced microglial activation via the NF-κB pathway. Furthermore, XBJ was found to inhibit microglial activation in TBI mice.</p><p><strong>Conclusion: </strong>These findings indicate that XBJ and HSYA may treat TBI by repressing microglial activation through the NF-κB pathway. Our study provides valuable evidence supporting XBJ as an effective therapy for TBI.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986132","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}