Combinatorial chemistry & high throughput screening最新文献

{"title":"Integrative Network Pharmacology, Molecular docking and Experimental Validation Uncover the Mechanism of Detoxifying Fumigation and Washing Granules against Hemorrhoids.","authors":"Zhi Chang, Xuhong Shao, Yuhua Li, Fang Zhang, Liwen Zeng, Wenbo Li, Meidong Si, Yaping Jiang, Ru Zhou","doi":"10.2174/0113862073485357260927072628","DOIUrl":"https://doi.org/10.2174/0113862073485357260927072628","url":null,"abstract":"<p><strong>Introduction: </strong>Hemorrhoids significantly impair the quality of life of patients, primarily manifesting as pain, bleeding, and prolapse. Detoxifying fumigation and washing granules (DFWG), a traditional Chinese medicine, have demonstrated potential for alleviating hemorrhoids; however, its underlying mechanisms of action have yet to be fully elucidated. This study aimed to investigate the putative active constituents and possible mechanisms of DFWG in the treatment of hemorrhoids.</p><p><strong>Methods: </strong>Active compounds in DFWG were identified through network pharmacology, and targets were screened using protein-protein interaction (PPI) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify core signaling pathways, and in vivo validation was conducted in a rat model of perianal edema.</p><p><strong>Results: </strong>Network pharmacology identified 328 active compounds and 1020 targets from DFWG, along with 314 hemorrhoid-related targets, yielding 46 overlapping targets. PPI analysis revealed 10 core targets, while GO and KEGG analyses indicated roles in regulating apoptosis and inflammation. Molecular docking results indicated that the binding energies between core target proteins and compounds were consistently below -5.0 kcal/mol. In vivo, DFWG reduced perianal swelling and rectoanal coefficient in model rats, lowered serum IL-1β, TNF-α, and IL-6, and suppressed p-NF-κB p65/NF-κB p65 expression in perianal tissues.</p><p><strong>Discussion: </strong>The findings of network pharmacology indicate that DFWG primarily alleviates hemorrhoidal symptoms by modulating key inflammatory mediators. This mechanism is further supported by the observed reduction in inflammatory responses in model rats, along with concurrent improvements in pathological manifestations.</p><p><strong>Conclusion: </strong>DFWG exerts protective effects against hemorrhoids in rats, likely by suppressing inflammation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179894","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 Protective Effect of Xiangsha Yangwei Pills on Alcohol-Induced Gastric Injury Using an Integrated Approach.","authors":"Yuxiang Huang, Yang Zhou, Shuaijun Guo, Chengsi Wu, Xinru Shao, Chenlu Liu, Xinting Cui, Li Li, Hao Zang, Guangqing Xia","doi":"10.2174/0113862073482825260917105544","DOIUrl":"https://doi.org/10.2174/0113862073482825260917105544","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Alcohol-induced gastric injury is a common clinical problem with few good preventive options. In this study, we examined whether Xiangsha Yangwei Pills (XS), a traditional herbal formula used for digestive issues, could protect against ethanol-induced gastric damage and sought to elucidate how it might work.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We combined network toxicology and network pharmacology to identify the main active compounds in XS and their potential biological targets. Two key components that emerged from this analysis, quercetin and borneol, were then examined using computational methods to predict their antioxidant activity-specifically their electron-acquisition ability and frontier orbital energy gaps. We also conducted in vitro experiments to directly test how well XS scavenges free radicals and chelates metal ions. For in vivo testing, we used a mouse model of alcohol-induced gastric injury and measured parameters such as gastric mucosal lesion severity, ulcer index scores, and total ulcer area to assess whether XS had a protective effect.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The network analysis identified nineteen central targets, many of which were antioxidant-related enzymes such as superoxide dismutase, catalase, and myeloperoxidase. Our computational results suggested that the main active compounds have strong antioxidant potential, which was supported by the in vitro findings, showing that XS effectively scavenges free radicals and chelates metal ions. In the animal model, administering XS beforehand significantly reduced gastric mucosal damage, reducing both ulcer scores and the affected area by more than 80%. At the molecular level, XS treatment increased the activity of the body's own antioxidant enzymes (superoxide dismutase, catalase) and reduced tissue levels of oxidative stress markers such as malondialdehyde and myeloperoxidase.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The integration of network toxicology and pharmacology revealed 19 overlapping targets, predominantly antioxidant enzymes, suggesting that the gastroprotective effect of XS is mechanistically mediated by mitigating oxidative stress. This computational prediction was empirically validated by the observed increase in superoxide dismutase and catalase activities and the reduction in malondialdehyde and myeloperoxidase levels in vivo. Notably, the high binding affinities of core components such as quercetin and borneol to key targets (e.g., AKT1, TNF, TP53) suggest that XS may exert synergistic, multi-target modulation beyond direct radical scavenging, potentially influencing cell survival and inflammatory pathways. These findings position XS as a promising multi-component strategy for managing alcohol-induced gastric injury, bridging traditional use with modern mechanistic evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, our findings show that XS offers strong protection against alcohol-induced gastric injury. The main mechanism","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179912","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":"Danggui Shaoyao Powder Alleviates MAFLD by Regulating the AMPK/Nrf2/NF-κB Signaling Pathway.","authors":"Yaning Biao, Xinqiao Chu, Xingxing Gao, Dou Zhang, Ying Gu, Yafen Wang, Yixin Zhang","doi":"10.2174/0113862073477943260930051022","DOIUrl":"https://doi.org/10.2174/0113862073477943260930051022","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the mechanisms by which Danggui Shaoyao powder (DSP) treats metabolic dysfunction-associated fatty liver disease (MAFLD).</p><p><strong>Methods: </strong>The MAFLD rats were established by feeding a high-fat diet (HFD). After 12 weeks of modeling, DSP treatment was administered simultaneously with the modeling for 4 weeks. Parameters assessed included lipid metabolism, liver function, oxidative stress, inflammatory factors, and reactive oxygen species (ROS) levels. Hepatic histopathological changes were also evaluated. Proteins associated with the AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor-κB (NF-κB) signaling pathway were analyzed using western blot. Additionally, the involvement of the AMPK/Nrf2/NF-κB signaling pathway in palmitic acid (PA)-induced HepG2 cells was confirmed using an AMPK activator and AMPK and Nrf2 inhibitors.</p><p><strong>Results: </strong>Findings demonstrated that DSP effectively regulated lipid metabolism, improved liver function, and reduced oxidative injury and inflammation in MAFLD rats. In PA-treated HepG2 cells, DSP significantly decreased lipid accumulation, oxidative stress, and inflammation. Furthermore, DSP increased AMPK phosphorylation, leading to Nrf2 activation and inhibition of NF-κB phosphorylation in both MAFLD rats and HepG2 cells.</p><p><strong>Conclusion: </strong>The results indicate that DSP mitigates oxidative damage and inflammation associated with MAFLD, likely by modulating the AMPK/Nrf2/NF-κB signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179873","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":"Efficacy and Safety of Acupoint Catgut Embedding Combined with Hormone Replacement Therapy versus Sham Acupoint Embedding Combined with Hormone Replacement Therapy for Diminished Ovarian Reserve: A Single-Blind Randomized Controlled Trial.","authors":"Yijin Zhang, Wei Sun, Jianting Lao, Yueping Wang, Jiahui Li, Yunlan Wang, Yao Wang, Hong Yang","doi":"10.2174/0113862073473958260916111037","DOIUrl":"https://doi.org/10.2174/0113862073473958260916111037","url":null,"abstract":"<p><strong>Introduction: </strong>To investigate the differences in efficacy between Hormone Replacement Therapy (HRT) combined with Acupoint Catgut Embedding (ACE) and HRT combined with Sham Acupoint Embedding (SAM) in patients with Diminished Ovarian Reserve (DOR).</p><p><strong>Methods: </strong>A prospective, multicenter, randomized, single blind, controlled trial design was employed. Participants were randomly allocated to either the HRT + ACE group or the HRT + SAM group. Active treatment lasted 3 menstrual cycles, followed by 3 cycles of follow-up. Serum AMH, AFC, Ovarian volume, and serum Testosterone (T), FSH, LH, Estradiol (E2), Prolactin (PRL), and Cytokines (IL-2, IL-6, IL-17) levels were measured pre-treatment and post 3- treatment cycles and at follow-up for 3 treatment cycles.</p><p><strong>Results: </strong>In the treatment group, after 3 treatment cycles, AMH levels increased from baseline (P < 0.05). AFC, ovarian volume, and E2 all increased significantly in both groups compared with baseline (P < 0.05). Basal FSH (bFSH), basal LH (bLH), and IL-2 levels significantly decreased in the two groups (P < 0.05). All indicators in the treatment group at both post-treatment and 3- month follow-up were significantly better than baseline (P < 0.05). The treatment group was better than the control group in terms of AMH, AFC, bFSH, bLH, and IL-2 after 3 months and 6 months follow-up (P < 0.05). No serious adverse events occurred in either group.</p><p><strong>Discussion: </strong>This study demonstrates that HRT combined with ACE can regulate neuroendocrine function, stimulate the reproductive axis, and modulate HPO axis function to improve ovarian function. Although ACE cannot normalize ovarian function, it optimizes follicle development and menstruation. It is a promising low-risk alternative for HRT-intolerant DOR patients.</p><p><strong>Conclusion: </strong>HRT combined with ACE can improve certain ovarian reserve indicators, including increasing AMH levels, AFC, and ovarian volume in DOR patients, with effects superior to those of HRT combined with SAM, suggesting that HRT combined with ACE may enhance ovarian function in DOR patients.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179906","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":"Study of the Mechanism of Xianglian Anchang Decoction Ameliorating Ulcerative Colitis Based on Transcriptomics and Network Pharmacology Analysis.","authors":"Tianyu Gao, Cuimei Zhao, Lishan Lu, Ziyue Luo, Chen Wang, Junzhuo Ma, Xuetong Ren, Xiaosong Xu, Jiong Chen, Jingjing Lv, Shixiong Zhang, Qian Yang, Yangang Wang","doi":"10.2174/0113862073486769260919093835","DOIUrl":"https://doi.org/10.2174/0113862073486769260919093835","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The therapeutic efficacy of Xianglian Anchang Decoction (XLAC) in Ulcerative Colitis (UC) has been established, but the underlying pharmacological mechanisms have remained poorly elucidated. In this study, we employed an integrated strategy combining network pharmacology, transcriptomic profiling, and in vivo experimentation to reveal these mechanisms, with a particular focus on how XLAC modulates the IL-17/AP-1 signaling axis to attenuate intestinal inflammation and promote mucosal repair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;UC was induced in mice by 2% Dextran Sulfate Sodium (DSS) administration in drinking water. The animals were randomly divided into five groups: control (untreated), model (DSS only), XLAC-L (12.4 g/kg/day XLAC extract), XLAC-H (24.8 g/kg/day XLAC extract), and sulfasalazine reference (SASP) (5 g/kg/day sulfasalazine reference drug). Following a 7-day treatment period, various parameters were evaluated, including body mass fluctuations, colon dimensions, microscopic tissue alterations, and intestinal barrier integrity biomarker levels. A computational target prediction analysis was performed to elucidate the pharmacological mechanisms of XLAC, with subsequent transcriptome sequencing verification. Analytical techniques including fluorescence-activated cell sorting, protein immunoblotting, and tissue staining were employed to investigate the modulatory impact of XLAC on UC via the IL-17/AP-1 molecular cascade. Molecular docking and molecular dynamics simulations were performed to evaluate constituent-target binding and complex stability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;XLAC significantly prevented DSS-induced body weight loss, preserved colon length, and reduced the severity of colonic histopathological injury. The XLAC intervention suppressed the secretion of inflammatory mediators such as IL-6 and TNF-α, while concurrently promoting the expression of the tight junctional protein ZO-1. Integrated network pharmacology and transcriptomic profiling identified the IL-17 signaling pathway as a potential mechanism underlying the therapeutic effect of XLAC against UC. Further experiments validated that XLAC decreased IL-17A levels and inhibited both the expression and phosphorylation of the AP-1 transcription factors c-Jun and c-Fos. Molecular docking revealed stable binding between the principal bioactive constituents of XLAC (β-sitosterol and quercetin) and the c-Jun/c-Fos protein complex. Molecular dynamics simulations demonstrate the structural stability of the β-sitosterol-c-FOS complex.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Our findings reveal a critical role of the IL‑17/AP‑1 signaling axis in the pathogenesis of Ulcerative Colitis (UC) and demonstrate that XLAC may exert its therapeutic effects through this pathway. The multi‑target regulatory mechanism of XLAC provides a molecular basis for its superior efficacy and fewer side effects compared with conventional single‑target therapies. These data ","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165053","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 Therapeutic Efficacy and Molecular Mechanisms of Fu-zheng-yi-qi Recipe in Ameliorating Cancer Cachexia-associated Muscle Atrophy.","authors":"Guangran Hu, Xuan Li, Yinqiu Wu, Shengzhe Zhang, Guilan Jin, Ning Ding, Jun Zhang, Hua Dai","doi":"10.2174/0113862073496059260917104847","DOIUrl":"https://doi.org/10.2174/0113862073496059260917104847","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer Cachexia (CC) is a systemic wasting syndrome characterized by persistent skeletal muscle depletion. This study aims to systematically evaluate the therapeutic effect of the Fu-zheng-yi-qi recipe (FZYQR) against CC and to explore the potential molecular mechanisms underlying its ameliorative effects on muscle atrophy.</p><p><strong>Methods: </strong>The components of FZYQR were characterized using UPLC-Class Plus/VION IMS QTof. Pharmacological network analysis was performed to predict the therapeutic targets of FZYQR. An in vivo tumor cachexia model was established by subcutaneously implanting C26 tumor cells into male BALB/c mice. The therapeutic efficacy of FZYQR was evaluated by monitoring changes in body weight, grip strength, skeletal muscle mass, pathological progression, blood biochemical parameters, and inflammatory cytokine levels. The therapeutic mechanism underlying muscle atrophy was validated by qPCR and Western blot.</p><p><strong>Results: </strong>Among the major bioactive components of FZYQR, luteolin and quercetin play critical roles in treating CC. FZYQR significantly ameliorated muscle atrophy and associated symptoms in a well-established mouse model of CC. Mechanistically, upon FZYQR intervention, the expression level of JUN in skeletal muscle tissues of cachectic mice was markedly inhibited, accompanied by downregulation of the muscle atrophy biomarkers Atrogin-1 and MuRF1.</p><p><strong>Discussion: </strong>The specific mechanism underlying CC-induced muscle atrophy remains to be further elucidated. This study demonstrates the therapeutic potential of FZYQR for CC, and also provides a research strategy for the future development of natural products with anti-muscle atrophy effects.</p><p><strong>Conclusion: </strong>FZYQR exerts protective effects against CC-induced muscle atrophy, potentially through the modulation of the JNK/c-Jun signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168540","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":"Metal Nanoparticles as Modulators of the NF-κB Signaling Pathway: Emerging Concepts in Inflammation Research.","authors":"Suraj N Mali, Gerald H Lushington","doi":"10.2174/0113862073516316260910115503","DOIUrl":"https://doi.org/10.2174/0113862073516316260910115503","url":null,"abstract":"<p><p>The NF-κB signaling pathway is a key regulator of inflammation and an attractive therapeutic target in inflammatory diseases. Metal nanoparticles (MNPs) have emerged as promising modulators of this pathway through mechanisms involving reactive oxygen species, IκBα degradation, p65 nuclear translocation, and crosstalk with MAPK, PI3K/AKT, JAK/STAT, Nrf2, and NLRP3 signaling. This editorial summarizes recent advances in the dual immunomodulatory roles of MNPs, highlighting how their composition, size, surface characteristics, and dose determine their pro- or anti-inflammatory effects.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105197","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":"Metabolomic Fingerprints of L-PRP and P-PRP: Formulation differences and Storage-induced Shifts.","authors":"Emine Koç, Bilge Başak Fidan, Ozan Kaplan, Petek Korkusuz, Emine Ciftci, Mustafa Çelebier, Feza Korkusuz","doi":"10.2174/0113862073509062260915135412","DOIUrl":"https://doi.org/10.2174/0113862073509062260915135412","url":null,"abstract":"<p><strong>Introduction: </strong>Platelet-rich plasma (PRP) preparation and storage conditions are thought to influence its clinical efficacy in osteoarthritis; however, molecular evidence supporting this assumption remains limited. This study aimed to compare the metabolomic profiles of leukocyte- rich PRP (L-PRP) and pure/leukocyte-poor PRP (P-PRP) and to evaluate the effect of shortterm frozen storage on their metabolite composition.</p><p><strong>Methods: </strong>L-PRP and P-PRP samples were collected from six healthy male donors and analysed using untargeted quadrupole time-of-flight liquid chromatography-mass spectrometry (Q-TOF LC/MS)-based metabolomics. Each sample was analysed immediately after preparation and after one week of storage at -20 °C. Multivariate and univariate statistical analyses were performed to identify formulation-specific and storage-related metabolic alterations.</p><p><strong>Results: </strong>Distinct metabolomic differences were observed between L-PRP and P-PRP. L-tyrosine, D-glucuronic acid, nicotinamide ribotide, and epinephrine were among the metabolites that best discriminated the two formulations. Frozen storage induced formulation-dependent metabolic changes. In L-PRP, nicotinamide ribotide and prostaglandin H2 changed, whereas P-PRP showed alterations in phosphocreatine, citric acid, and glutathione. These changes were consistent across all donors.</p><p><strong>Discussion: </strong>Both PRP formulation and frozen storage influenced metabolite composition, indicating that biochemical differences extend beyond platelet and leukocyte content. Although the clinical significance of these alterations remains unclear, they may contribute to differences in PRP biological activity. Further studies integrating metabolomic and proteomic analyses are needed.</p><p><strong>Conclusion: </strong>Short-term frozen storage induces reproducible, formulation-dependent metabolomic changes in PRP. These findings emphasize the importance of storage conditions and provide a basis for future studies investigating their impact on PRP therapeutic efficacy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105194","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":"Screening of Programmed Cell Death-Related Biomarkers and Exploration of Mechanisms in Zhenwu Decoction for Treating Chronic Kidney Disease.","authors":"Ruiping Li, Tao Zhang, Liuyun Li, Xingyao Li, Qi Gao, Xili Wu, Sicen Wang, Peng An","doi":"10.2174/0113862073423674260909100001","DOIUrl":"https://doi.org/10.2174/0113862073423674260909100001","url":null,"abstract":"<p><strong>Introduction: </strong>Programmed Cell Death (PCD) is pivotal in Chronic Kidney Disease (CKD), yet the therapeutic mechanism of Zhenwu Decoction (ZWD) targeting PCD remains unclear. This study integrated CKD transcriptomics (GSE15072 dataset) and network pharmacology to identify PCD-related biomarkers and elucidate ZWD's action.</p><p><strong>Methods: </strong>Differential expression analysis identified CKD-related genes. Active ZWD ingredients and targets were screened via TCMSP. Overlapping genes from PCD-Related Genes (PCDRGs), Differentially Expressed Genes (DEGs), and ZWD targets were subjected to machine learning for biomarker selection. Biomarkers were validated through nomogram construction, enrichment analysis, immune infiltration assessment, molecular docking, and RT-qPCR.</p><p><strong>Results: </strong>TCMSP identified 61 active ingredients and 777 targets for ZWD; 14 candidate genes were screened from 822 DEGs, 1548 PCD-RGs, and ZWD targets. Machine learning yielded 5 downregulated CKD biomarkers (SQLE, PRKACA, PARP2, RPS6KB1, ALOX12) with a wellperforming nomogram. GSEA linked SQLE, PRKACA, and ALOX12 to SARS-CoV-2 nsp1- related translation initiation; PARP2/RPS6KB1 negatively correlated with effector memory CD8 T cells, γδ T cells, NK cells, and neutrophils. PARP2 bound ignavine (Aconiti Lateralis Radix Praeparata) with -11.6 kcal/mol; RT-qPCR confirmed significant downregulation of 4 biomarkers, with PRKACA showing no difference.</p><p><strong>Discussion: </strong>CKD is a global burden with unclear mechanisms, in which dysregulated PCD worsens renal injury; ZWD has clinical efficacy in CKD, but its PCD-related targets were unknown. This study identified five downregulated biomarkers (SQLE, PRKACA, PARP2, RPS6KB1, ALOX12) via integrative bioinformatics and machine learning, which participate in lipid metabolism, inflammation, oxidative stress, and ferroptosis. PARP2 binds ZWD-derived ignavine (-11.6 kcal/mol), biomarkers correlate with immune cells, and ZWD exerts renoprotection by regulating PCD, immune homeostasis, and DNA repair, providing novel therapeutic insights.</p><p><strong>Conclusion: </strong>SQLE, PRKACA, PARP2, RPS6KB1, and ALOX12 were recognized as PCDrelated biomarkers for ZWD treatment of CKD, providing important references for the mechanism and clinical application of ZWD treatment of CKD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105115","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":"Cuscuta chinensis Lam. Ameliorates Pulmonary Arterial Hypertension via the PI3K/Akt/mTOR/HIF-1α Pathway: Evidence from Network Pharmacology and In Vivo Validation.","authors":"Liwei Wang, Rui Wang, Jie Wang, Qin Luo, Yun Wu","doi":"10.2174/0113862073517454260913163238","DOIUrl":"https://doi.org/10.2174/0113862073517454260913163238","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary Arterial Hypertension (PAH) is a progressive and lifethreatening cardiopulmonary disorder, primarily characterized by sustained elevation of pulmonary vascular resistance and structural remodeling of pulmonary vessels, which eventually leads to right ventricular failure and death. Cuscuta chinensis Lam. (CCL), a traditional medicinal herb from Xinjiang, has been reported to exert cardiovascular protective effects, including antiinflammatory, antioxidant, and pro-apoptotic activities. Nevertheless, the precise pharmacological role of CCL in alleviating PAH and the molecular mechanisms underlying this effect remain largely unexplored.</p><p><strong>Methods: </strong>The therapeutic efficacy of CCL was first evaluated in an MCT-induced rat model of PAH by measuring mean Pulmonary Artery Pressure (mPAP), mean Right Ventricular Pressure (mRVP), and pulmonary vascular remodeling. Network pharmacology was subsequently used to identify the potential bioactive compounds, candidate targets, and enriched signaling pathways associated with the observed therapeutic effects. Molecular docking was performed to evaluate the predicted interactions between the principal compounds and selected target proteins. Finally, the predicted PI3K/Akt/mTOR/HIF-1α pathway was examined using RT-qPCR and Western blotting.</p><p><strong>Results: </strong>CCL treatment significantly reduced mPAP and mRVP, and ameliorated pulmonary arterial wall thickening and luminal narrowing in MCT-induced PAH rats. These findings provided direct in vivo evidence of CCL's therapeutic effects against experimental PAH. Subsequent network pharmacology identified 64 overlapping targets between CCL-associated and PAHassociated target sets, with quercetin and kaempferol emerging as principal candidate compounds. Enrichment and docking analyses implicated the PI3K/Akt/mTOR/HIF-1α signaling axis. Consistent with this prediction, CCL reduced PI3K and Akt phosphorylation and downregulated mTOR and HIF-1α expression in lung tissues.</p><p><strong>Discussion: </strong>The study's findings demonstrate that CCL effectively ameliorates the core pathological features of PAH. These favorable outcomes are potentially associated with the suppression of inflammatory responses, the disruption of the PI3K/Akt/mTOR/HIF-1α pathway, and the prevention of structural vascular remodeling. Furthermore, although key regulatory targets were validated, the broader predicted interactome requires further experimental scrutiny.</p><p><strong>Conclusion: </strong>This study revealed that CCL alleviates PAH potentially by suppressing the PI3K/Akt/mTOR/HIF-1α signaling pathway. This provides new insights into the identification and utilization of Xinjiang's distinctive medicinal plants for the treatment of PAH.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079734","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}