Combinatorial chemistry & high throughput screening最新文献

{"title":"Qihuang Zhuyu Formula Attenuates Myocardial Ischemia Reperfusion Injury by Regulating Autophagy via the NF-κB P65/TRAIL Pathway.","authors":"Siyuan Yin, Manlu Fan, Chunxiao Wang, Jie Han, Songyi Cheng, Tong Sun, Peng Xue, Yuhan Ding, Mengxi Wang, Qian Xiang, Xiaohu Chen, Huaqin Tong","doi":"10.2174/0113862073479699260416070028","DOIUrl":"https://doi.org/10.2174/0113862073479699260416070028","url":null,"abstract":"<p><strong>Introduction: </strong>Myocardial Ischemia Reperfusion Injury (MIRI) contributes to adverse cardiovascular outcomes. Dysregulated myocardial autophagy plays a key role in MIRI, yet therapeutic strategies targeting this process are limited. Qihuang Zhuyu Formula (QHZYF), a traditional Chinese herbal compound, exhibits cardiovascular protective effects, but its molecular mechanism in MIRI remains unclear. The NF-κB P65/TRAIL signaling axis regulates autophagy in MIRI and may serve as a critical target for QHZYF intervention.</p><p><strong>Methods: </strong>QHZYF components were analyzed using UPLC-Q-TOF-MS. Network pharmacology identified the NF-κB P65/TRAIL pathway as a core mechanism. In vivo, a rat MIRI model was treated with QHZYF; myocardial injury was assessed via histology, electrocardiography, echocardiography, immunohistochemistry, western blot, and RT-qPCR. In vitro, H9C2 cells underwent hypoxia/reoxygenation and were treated with QHZYF. Autophagy and pathway-related markers, including NF-κB p65, TRAIL, Beclin 1, LC3, and P62, were measured.</p><p><strong>Results: </strong>Network pharmacology and experimental results confirmed that QHZYF targets NF-κB P65/TRAIL to restore myocardial autophagic homeostasis. Treatment reduced cardiomyocyte injury and normalized autophagy markers in both in vivo and in vitro models.</p><p><strong>Discussion: </strong>This study demonstrates that QHZYF exerts cardioprotective effects against MIRI by regulating autophagy and suppressing NF-κB P65/TRAIL signaling. Integration of compound analysis and experimental models revealed the pathway's key role in autophagic imbalance and myocardial injury. QHZYF intervention restored autophagic homeostasis and mitigated cardiomyocyte damage, highlighting its potential application for MIRI prevention and therapy.</p><p><strong>Conclusion: </strong>QHZYF alleviates myocardial autophagy imbalance via the NF-κB P65/TRAIL pathway, providing mechanistic insight into its therapeutic potential in MIRI management.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981014","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":"sh-lncRNA-SNHG4 Regulates Cell Proliferation, Apoptosis, and EMT in Osteosarcoma Cells via Regulating miR-204-5p to Target LRP8.","authors":"Zhennan Tian, Huilei Qiu, Yaoguo Lang, Yang Zhou, Xiangjing Yu","doi":"10.2174/0113862073444907260321211329","DOIUrl":"https://doi.org/10.2174/0113862073444907260321211329","url":null,"abstract":"<p><strong>Introduction: </strong>To explore the function of the LncRNA SNHG4/miR-204-5p/LRP8 axis in the development of osteosarcoma (OS), especially in the process of epithelial-mesenchymal transition (EMT).</p><p><strong>Methods: </strong>The expression of SNHG4 was evaluated between various human OS cell lines, and 143B cell lines were screened out. Lentiviral vectors were used to interfere with the expression of SNHG4 and LRP8, while overexpressing the expression of miR-204-5p. The abilities of cell proliferation, migration, invasion, and apoptosis were evaluated by CCK-8, Transwell, and flow cytometry, respectively. The expression of related proteins (such as EMT markers, etc.) was detected by qRT-PCR and Western Blot. The dual-luciferase reporter gene assay verified the targeting relationship between miR-204-5p and LRP8. In vivo, the transplanted tumor model was established, and the role of this pathway was further verified, combined with immunohistochemistry and Western Blot.</p><p><strong>Results: </strong>SNHG4 is significantly highly expressed in OS cells, especially in 143B cells. In vivo, sh-lnc-SNHG4, ov-miR-204-5p, or sh-LRP8 can effectively inhibit the proliferation, migration, and invasion of OS cells and promote their apoptosis, while reversing the EMT process. SNHG4 may act as a competitive endogenous RNA to adsorb miR-204-5p, thereby relieving the inhibitory effect of miR-204-5p on its target gene LRP8 and further activating the Wnt/β-catenin pathway. In vivo experiments have confirmed that intervention in this pathway can significantly inhibit the growth of tumors in nude mice.</p><p><strong>Discussion: </strong>This study highlights the oncogenic role of lncRNA-SNHG4, which is highly expressed in OS and associated with tumor progression, while miR-204-5p has been reported to be a tumor suppressor. Inhibiting lncRNA- SNHG4 or overexpressing miR-204-5p suppressed OS cell proliferation, migration, invasion, and EMT, and promoted apoptosis by targeting LRP8. Consistently, sh-lnc-SNHG4 or ov-miR-204-5p reduced tumor growth and EMT in vivo.</p><p><strong>Conclusion: </strong>The lncRNA SNHG4/miR-204-5p/LRP8 axis plays a critical role in OS and may serve as a potential therapeutic target.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981011","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":"Coptidis Rhizoma and Rheum officinale Supplementation Protects β-cells in Diabetic Rats by Suppressing the NLRP3 Inflammasome and Regulating the Gut Microbiota.","authors":"Zhenhua Li, Boxun Zhang, Maoyi Yang, Rensong Yue, Yuan Chen","doi":"10.2174/0113862073458542260409114205","DOIUrl":"https://doi.org/10.2174/0113862073458542260409114205","url":null,"abstract":"<p><strong>Introduction: </strong>Coptidis Rhizoma and Rheum Officinale (CR) are frequently used herbs in traditional Chinese medicine for managing Type 2 Diabetes Mellitus (T2DM). This study investigated the protective effects of CR on pancreatic β-cells in T2DM rats and elucidated the underlying mechanisms.</p><p><strong>Methods: </strong>A T2DM model was established using spontaneously diabetic Goto-Kakizaki (GK) rats. GK rats were administered varying doses of CR (low, mid, and high) for 8 weeks via gavage. After this period, changes in glycolipid levels, histopathology, insulin signalling pathways, NLRP3 inflammasome-related proteins, and gut microbiota were examined.</p><p><strong>Results: </strong>CR treatment exerted modulatory effects on glucolipid metabolism disorders in GK rats, ameliorating histopathological injury to the pancreas. It increased insulin-positive cell expression and secretion, reduced cell death, lowered the levels of NLRP3, ASC, and caspase 1 proteins, and enhanced insulin signal transduction. Additionally, it regulated gut microbiota, promoting microbiota richness and diversity and restructuring its equilibrium at various taxonomic levels, including the phylum and genus levels.</p><p><strong>Discussion: </strong>Our results demonstrate that CR supplementation concurrently suppresses the NLRP3 inflammasome pathway and modulates the gut microbiota, both of which are implicated in β-cell protection. While the precise interplay between these two systems in the context of CR treatment requires further investigation, the coordinated suppression of inflammation and amelioration of gut dysbiosis highlight a potential multi-targeted mechanism of action for this herbal formulation, which aligns with the holistic principles of traditional Chinese medicine.</p><p><strong>Conclusion: </strong>CR exerts protective effects on pancreatic β-cells, which are associated with the suppression of NLRP3 inflammasome activation-mediated inflammatory responses and modulation of gut microbiota.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980944","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":"Chuangling Liquid Mitigates Plasma Cell Mastitis via STAT3 Pathway Inhibition: Pharmacological and Experimental Insights.","authors":"Ti Zhang, Shikun Ma, Ming Reng, Jianzhong Shi, Chang Yao","doi":"10.2174/0113862073424052260305133726","DOIUrl":"https://doi.org/10.2174/0113862073424052260305133726","url":null,"abstract":"<p><strong>Introduction: </strong>Chuangling Liquid (CLL) is a clinically effective preparation for inflammatory and ulcerative wounds; however, its systematic pharmacological mechanisms, particularly for plasma cell mastitis (PCM), remain largely unexplored. This study aims to evaluate the therapeutic potential of CLL in PCM and clarify its potential molecular mechanism, focusing on the STAT3 signaling pathway.</p><p><strong>Methods: </strong>An integrated method combining network pharmacology and validation in vivo was used. The common target between CLL and PCM was identified by network pharmacological analysis. Molecular docking was performed to evaluate the binding interactions between key CLL compounds and core targets. The mouse PCM model was used for experimental verification, including measurements of phosphorylated STAT3, inflammatory cytokines, macrophage polarization, and collagen deposition. A STAT3 agonist was co-administered to confirm the pathway-specificity of CLL effects.</p><p><strong>Results: </strong>STAT3 was identified as the central target. Myricetin, a bioactive component of CLL, showed ultra-strong binding to STAT3 (-9.2 kcal/mol). In vivo, CLL dose-dependently inhibited STAT3 phosphorylation by 92%, reduced IL-1β and TNF-α levels by 85% and 81%, respectively, promoted M2 macrophage polarization (4.2-fold increase in CD206), and enhanced collagen1 expression (5.75-fold). All therapeutic effects were abolished by STAT3 activation.</p><p><strong>Discussion: </strong>CLL alleviates PCM through potent inhibition of the STAT3 pathway, disrupting the IL-6/STAT3 inflammatory feedback loop, reducing cytokine release, promoting M2 macrophage polarization, and restoring tissue homeostasis.</p><p><strong>Conclusion: </strong>These findings provide a mechanistic basis for the clinical application of CLL, and emphasize its multi-target anti-inflammatory and tissue repair properties.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980877","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":"Microbiome and Lipidomics Reveal the Mechanism of Eight Zhes Decoction on MAFLD.","authors":"Daijun Lu, Jingxuan Lu, Ping Yang, Linjie Lou, Wenjie Li, Yuping Zhou","doi":"10.2174/0113862073460107260407065758","DOIUrl":"https://doi.org/10.2174/0113862073460107260407065758","url":null,"abstract":"<p><strong>Introduction: </strong>The therapeutic potential of Eight Zhes Decoction (EZD) against metabolic dysfunction-associated fatty liver disease (MAFLD) is well-recognized; however, the underlying biological pathways are not well understood. To address this gap, an integrated investigation using both lipidomics and metagenomics was conducted to reveal the mechanistic rationale behind the effects of EZD.</p><p><strong>Methods: </strong>A MAFLD mouse model was established using a Methionine-Choline-Deficient (MCD) diet combined with CCl₁. The mice were treated with EZD for four weeks. Hepatic injury was assessed via H&E, Oil Red O, and Masson staining. Untargeted hepatic lipidomics and shotgun metagenomics were employed to profile lipid species and the gut microbiota composition, respectively.</p><p><strong>Results: </strong>Histopathological analysis confirmed that EZD significantly alleviated hepatic steatosis, ballooning degeneration, and fibrosis. Lipidomics identified 277 differential lipids; EZD treatment notably downregulated 24 TGs and modulated pathways related to arachidonic acid metabolism and bile secretion. Metagenomics revealed that EZD reshaped the gut microbiota, significantly increasing the abundance of Alistipes sp. while reducing the abundance of Faecalibaculum rodentium.</p><p><strong>Discussion: </strong>Correlation analysis demonstrated that the restored Alistipes sp. was negatively correlated with multiple hepatic TGs, whereas Faecalibaculum rodentium was positively correlated with lipid accumulation.</p><p><strong>Conclusion: </strong>EZD mitigates MAFLD in mice by synergistically regulating hepatic lipid metabolism and gut microbiota. Specifically, the therapeutic effect involves restoring Alistipes sp. and modulating the gut-liver axis, providing experimental evidence for the clinical application of EZD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980899","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":"Ethnopharmacology, Phytochemistry, and Pharmacology of Lophatheri Herba (Dan-Zhu-Ye): A Comprehensive Review and Future Perspectives.","authors":"Zuoliang Zheng, Lihui Mou, Zhiwei Liu, Yulin He, Jiaying Li, Xinran Xiong, Yuping Zhong","doi":"10.2174/0113862073455119260424073215","DOIUrl":"https://doi.org/10.2174/0113862073455119260424073215","url":null,"abstract":"<p><p>Lophatheri Herba (LH), commonly referred to as Dan-Zhu-Ye, is a traditional Chinese medicine with both medicinal and edible applications. In recent decades, modern research has greatly expanded our understanding of its material basis and pharmacological potential. This review comprehensively synthesizes the current knowledge on LH. To date, a total of 89 phytochemical constituents have been isolated or identified, with flavonoids as the predominant class. Modern pharmacological studies have demonstrated that LH extracts and their key constituents, particularly the C-glycosylated flavonoids such as isoorientin, exhibit a wide range of bioactivities. These include hepatoprotection, anti-osteoporosis effects, antiviral properties, anticancer potential, and antibacterial action, suggesting a scientific basis for exploring its broader application beyond its traditional ethnomedicinal scope. This review comprehensively integrates findings from ethnopharmacology, phytochemistry, and pharmacology to bridge traditional wisdom with contemporary scientific evidence. However, several research gaps persist, including the identification of robust quality control biomarkers, insufficient mechanistic understanding of multitarget synergies among constituents, and a notable lack of clinical and safety evaluation data. Future in-depth studies on the material basis, precise mechanisms, and well-designed clinical trials are crucial for future investigations aimed at evaluating whether LH could serve as a source for therapeutic development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980950","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":"Mechanistic Insights into the Anti-Constipation Potential of Zeng Ye Tang Compound: UHPLC-Q-TOF MS/MS, Network Pharmacology, and In vivo Experimental Validation.","authors":"Xue Wu, Yan Wan, Linao Zhang, Shifang Luo, Feifan Liu, Yuanmei Bai, Qing Li, Xianjin Tang, Tao Li, Hua Tang, Yanyan Zhang, Yuhuan Xie, Peixin Guo","doi":"10.2174/0113862073433005251206045709","DOIUrl":"https://doi.org/10.2174/0113862073433005251206045709","url":null,"abstract":"<p><strong>Introduction: </strong>Zeng Ye Tang (ZYT) is used to treat constipation caused by various factors. However, the precise mechanism underlying its therapeutic effects remains unclear.</p><p><strong>Methods: </strong>An integrative approach combining UHPLC-Q-TOF MS analysis, network pharmacology, and in vivo validation was employed to elucidate the therapeutic basis of ZYT against constipation systematically.</p><p><strong>Results: </strong>The analysis identified 166 active ingredients in the ZYT formula, targeting 144 core constipation-related genes. ZYT modulated constipation progression primarily through the cAMP signaling pathway. Animal studies showed that ZYT treatment significantly increased defecation frequency and fecal water content. Additionally, ZYT alleviated histopathological damage in the colonic tissues of constipated mice, regulated serum levels of both excitatory and inhibitory neurotransmitters, and increased ET and VIP concentrations. ZYT also enhanced colonic protein expression of VIP, cAMP, PKA, and AQP3.</p><p><strong>Discussion: </strong>By integrating network pharmacology with experimental verification, this study confirmed that ZYT exerts therapeutic effects against constipation by regulating the VIP-cAMPPKA- AQP3 signaling axis. This pathway influences gastrointestinal motility, modulates neurotransmitter release, and regulates intestinal fluid and electrolyte secretion.</p><p><strong>Conclusions: </strong>ZYT demonstrates anti-constipation effects by modulating the VIP-cAMP-PKAAQP3 signaling pathway. These findings provide experimental support for its therapeutic potential and mechanism of action as a laxative, offering valuable guidance for clinical application.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980896","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":"Network Pharmacology and Experimental Validation to Investigate the Effects of Huatan Huoluo Decoction on Enhancing Lipid Metabolism Mechanism.","authors":"Yuan Wang, Huiying Zhou, Bo Wang, Hong Zhang, Kaihua Long, Yuxi Liu","doi":"10.2174/0113862073439918260410090027","DOIUrl":"https://doi.org/10.2174/0113862073439918260410090027","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperlipidemia (HLP) is a disorder of lipid metabolism, and dyslipidemia represents a major risk factor for Atherosclerosis (AS) and cardiovascular diseases. HuaTan HuoLuo (HTHL) Decoction, a Chinese herbal formulation, has demonstrated significant therapeutic efficacy in the clinical management of HLP. Nevertheless, the underlying molecular mechanisms by which HTHL exerts its lipid-lowering effects remain poorly understood.</p><p><strong>Methods: </strong>A combined strategy integrating network pharmacology analysis and experimental validation was employed to investigate the active components, key targets, and potential mechanisms of HTHL in the treatment of HLP. Body weight, liver index, and serum biochemical parameters were assessed. Histopathological alterations in the liver, kidney, heart, and aorta were evaluated using hematoxylin and eosin (H&E) staining. Furthermore, the pharmacological effects and molecular mechanisms of HTHL in hyperlipidemia (HLP) Sprague-Dawley (SD) rats were examined using Western blotting (WB), Reverse transcription-quantitative PCR (RTqPCR), immunofluorescence, and immunohistochemistry.</p><p><strong>Results: </strong>Network pharmacology analysis effectively identified 273 active components in HTHL Decoction and 121 potential therapeutic targets associated with HLP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 186 signaling pathways. The experimental results indicated that the anti-HLP effects of HTHL may be closely linked to key targets such as AKT1. Following HTHL administration, serum total cholesterol (TC) levels decreased to 1.69 ± 0.30 mmol/L, while Triglyceride (TG) levels decreased to 0.41 ± 0.13 mmol/L. WB revealed that HTHL significantly downregulated the expression of PI3K, AKT, phosphorylated AKT (p-AKT), and phosphorylated PI3K (p-PI3K). Immunofluorescence analysis showed that HTHL suppressed the expression of phosphorylated mTOR (p-mTOR), while immunohistochemical analysis indicated a marked reduction in PTEN expression.</p><p><strong>Discussion: </strong>Given the increasing global prevalence of metabolic disorders, elucidating the therapeutic efficacy and molecular mechanism of HTHL Decoction in HLP provides an important experimental basis and potential translational value for clinical application.</p><p><strong>Conclusion: </strong>This study suggests HTHL Decoction improves lipid metabolism, potentially through modulation of the PI3K-AKT signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980904","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 Effect and Mechanism of Zhuang Medicine Shuanglu Tongnao Formula in the Treatment of Cerebral Ischemia/Reperfusion Injury.","authors":"Yang Zhai, Yan Pang, Mingfu Pan, Kaihua Wang, Yuandai Luo, Xiaoping Mei, Ying Chen, Min Zou, Peng Yang, Wei Ma, Yangling Wu, Liang Liang","doi":"10.2174/0113862073428159260111142933","DOIUrl":"https://doi.org/10.2174/0113862073428159260111142933","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke (IS), characterized by high rates of disability and mortality, is among the most severe cerebrovascular diseases affecting the elderly. Shuanglu Tongnao Formula (SLT), a traditional Chinese Zhuang medicine, has been proposed as a prospective therapeutic agent for IS. However, the potential mechanism of the treatment of IS by SLT remains largely unknown. This study aimed to evaluate the therapeutic effect of SLT on IS and its possible mechanisms.</p><p><strong>Methods: </strong>The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established to induce focal cerebral ischemia/reperfusion (I/R) injury in male Sprague Dawley rats. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Ischemic brain tissue damage was evaluated by Haematoxylin-eosin staining and transmission electron microscopy. The serum levels of inflammation markers (TGF-β1 and TNF-α) and oxidative stress markers (ROS and MDA) were examined. Apoptotic markers (Bad, Cleaved Caspase-3, and Bcl-2), Blood-brain barrier (BBB) proteins (ZO-1, Occludin, and Claudin-5), and the activation of the TLR4/NF-κB signaling pathway were detected by Western blot (WB). The effect of SLT on gene expression of ischemic brain tissue was analyzed by RNA sequencing.</p><p><strong>Results: </strong>SLT attenuated I/R injury as evidenced by the reduction in the cerebral infarct volume and amelioration of the neurological deficits. Moreover, SLT mitigated cerebral histopathological damage, abnormal mitochondrial morphology, inflammation, and oxidative stress after cerebral I/R in rats. Additionally, SLT attenuated apoptosis and recovered BBB integrity in cerebral I/R rats. RNA sequencing revealed that SLT may alleviate cerebral I/R injury by regulating inflammation and oxidative stress signaling pathways in rats. WB results showed that SLT downregulated the protein expression of TLR4, p-NF-κB, and p-IκB after cerebral I/R in rats.</p><p><strong>Discussion: </strong>SLT can alleviate cerebral I/R injury in rats. Mechanistically, SLT may inhibit the activation of the TLR4/NF-κB signaling pathway, thereby limiting downstream inflammatory and oxidative stress cascades. These findings suggested that SLT exerts neuroprotective effects through anti-inflammatory and antioxidant mechanisms.</p><p><strong>Conclusion: </strong>SLT could alleviate cerebral I/R injury by inhibiting TLR4/NF-κB signaling pathways. Our study will enrich the theoretical foundation of SLT in the treatment of IS and promote its clinical application in managing IS.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970817","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 Antioxidant Paradox in Soccer: Striking the Balance between Protection and Performance.","authors":"Manaf AlMatar, Fatma Hassan Abd Elbasset Mourgan, Eman Abdelhalim Mohamed Ali, Nana ELDawy Ahmed Hefny, Wafaa Mohmoud Abdellatif Bekir","doi":"10.2174/0113862073442299260217110531","DOIUrl":"https://doi.org/10.2174/0113862073442299260217110531","url":null,"abstract":"<p><p>Antioxidants are also taken by athletes to facilitate recovery and performance, especially by soccer players, given their high-level physical activity, which has been reported to produce ROS that contribute to the severity of muscle injury and fatigue. However, ROS also act as signaling mediators, crucial for muscle adaptation and mitochondrial function. The recent study aims to discuss the potential dual role of antioxidant intake in soccer, emphasizing that chronic intake can inhibit adaptations via ROS signaling, whereas acute intake can be useful for athletes, especially during periods with congested fixtures. The study involves the role of vitamin C and vitamin E, Coenzyme Q10 (CoQ10), Docosahexaenoic Acid (DHA), polyphenols, as well as other commonly supplemented antioxidants with further explanation on the potential role of the time, dosage, and duration associated with recovery, findings showing potential enhanced recovery for soccer players following intake but with high dosage potentially associated with inhibited adaptations. Recommendations for soccer players, specifically coaches, relate to the appropriate timing of antioxidant supplementation to prevent inhibited adaptations following permissible levels of use during training.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970819","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}