Combinatorial chemistry & high throughput screening最新文献

{"title":"Paederia Foetida Linn (Rubiaceae): Chemical Diversity, Phytopharmacological Potential, Quantitative Analysis and Clinical Approaches.","authors":"Jyotsana Dwivedi, Pranay Wal, Vijay D Wagh, Pranjal Sachan, Neha Shukla Joshi, Swapnil Goyal, Arpan Kumar Tripathi","doi":"10.2174/0113862073314773241115100620","DOIUrl":"https://doi.org/10.2174/0113862073314773241115100620","url":null,"abstract":"<p><p>The discovery of novel counteractive pharmaceuticals, which have recently generated much interest, has played a significant role in the development of drugs derived from herbal medicines or botanical sources. Paederia foetida (P. foetida) is one such example of a role in both traditional and traditional medicine. Owing to its popularity in folk medicine, it has been the subject of intense pharmacological and chemical studies for the last 30 years. They are locally known as \"Gandhavadulia\" or \"GandhaPrasarini\" (English name \"skunkvine\") and belong to the family Rubiaceae. This plant has a broad range of applications in the treatment of several illnesses, including anti-inflammatory, antinociceptive, antitussive, thrombolytic, antidiabetic, antihyperlipidaemic, antioxidant, nephroprotective, anti-inflammatory, hepatoprotective, anthelmintic, and antidiarrheal effects. Additionally, it contains a variety of phytochemicals, such as asperuloside, paederosidic acid, sitosterols, campesterol, lignans, alkaloids, volatile oils, iridoids, methylindooxy substances, stigmasterol, tannins, triterpenoids, ellagic acid, ursolic acid, epifriedelinol, and phenolic compounds. Recently, mounting data on numerous active ingredients have indicated that they may be beneficial for spermatogenesis, wound healing, inflammatory illnesses, and cancer. This review describes the phytochemistry and mechanisms of action of these pharmacological effects and provides insights into potential pharmacological targets. These results highlight the need for additional studies on this medicinal plant and the investigation of new counteractive medications to determine their mode of action before use in healthcare.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945643","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 Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma.","authors":"Nuo Yao, Kexin Lin, Xiaodong Qu, Xuezhi Li, Xingyu Zhao, Songbo Li, Jie Zhang, Yongquan Shi","doi":"10.2174/0113862073353612241030061241","DOIUrl":"https://doi.org/10.2174/0113862073353612241030061241","url":null,"abstract":"<p><strong>Background: </strong>Stomach adenocarcinoma (STAD) is the fifth most common tumor worldwide, imposing a significant disease burden on populations, particularly in Asia. Oxidative stress is well-known to play an essential role in the occurrence and progression of malignancies. Our study aimed to construct a prediction model by exploring the correlation between oxidative stress-related genes and the prognosis of patients with STAD.</p><p><strong>Method: </strong>STAD data from TCGA were used to identify the differentially expressed oxidative stress-related genes (OSGs), with data from GEO serving as the validation cohort. Univariate Cox and LASSO regression analyses were performed to select prognosis-related genes for the risk model, which was then integrated with clinical features into a nomogram. The physiological functions and pathways of these identified genes were explored using GO and KEGG analyses. After evaluating the prediction value of the prognostic model in the GEO cohort, drug sensitivity and immune infiltration were comprehensively analyzed using R. Expression levels of the prognostic genes were verified by quantitative real-time PCR in gastric cancer and paired normal tissues.</p><p><strong>Results: </strong>Cox regression and LASSO regression analysis identified SERPINE1, VHL, CD36, NOS3, ANXA5, ADCYAP1, POLRMT and GPX3 as the signature genes from 160 differentially expressed OSGs. Both Kaplan-Meier survival analysis and ROC curve at 5 years in the TCGA and the GEO cohort exhibited great predictive ability of the prognostic model, with the AUC >0.7 in TCGA. Validated as an independent risk factor, the model was integrated with clinicopathological variables (including age, stage, and gender) to build a nomogram for more accurate risk stratification. Moreover, therapy sensitivity analysis between the low- and high-risk categories showed that those who scored higher would benefit more from BEZ235, Dasatinib, Pazopanib, and Saracatinib. Meanwhile, differences in the tumor environment, immune infiltration and response to immunotherapy between the two groups were noted. Finally, qRT-PCR validated the differential expression of these genes in STAD and paired normal tissues.</p><p><strong>Conclusion: </strong>Our study has effectively established an oxidative stress-related prognostic model, providing a promising tool for personalized clinical strategies and improved STAD patient outcomes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945861","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":"Exploration of the Mechanism of Tanre Qing Injection in Treating Acute Respiratory Distress Syndrome through Network Pharmacology, Molecular Docking, and Animal Experiments.","authors":"Liang Wang, Ganqun Lu, Tianyu Cheng, Shuangquan Wen, Wenxiang Ma, Yixuan Li","doi":"10.2174/0113862073331156241029074305","DOIUrl":"https://doi.org/10.2174/0113862073331156241029074305","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the active components and potential mechanism of Tanre Qing Injection (TRQI) in the treatment of Acute Respiratory Distress Syndrome (ARDS) using network pharmacology, molecular docking, and animal experiments.</p><p><strong>Methods: </strong>The targets of active ingredients were identified using the TCMSP and Swiss Target Prediction databases. The targets associated with ARDS were obtained from the GeneCards database, Mala card database, and Open Targets Platform. A Protein-protein Interaction network (PPI) was constructed, and the core targets were subjected to Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, molecular docking technology and a mouse model of lipopolysaccharide-induced acute lung injury validated the experimental results.</p><p><strong>Results: </strong>The results of network pharmacology showed the active components of TRQI in the treatment of ARDS to be baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid, and the core targets to be TP53, ESR1, AKT1, JUN, and SRC. KEGG analysis showed 181 signaling pathways, primarily including the IL-17 signaling pathway, endocrine resistance, lipid metabolism, and atherosclerosis. Molecular docking results demonstrated that baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid in TRQI exhibited the strongest affinity for TP53, ESR1, and SRC. Furthermore, the results of animal experiments have indicated TRQI to have a significant inhibitory effect on inflammatory factors TNF-α, IL-1β, and IL-6, and effectively alleviate the pathological damage of ARDS to lung tissue.</p><p><strong>Conclusion: </strong>TRQI may exert its therapeutic effects on ARDS through multiple targets and pathways, providing a research basis for its clinical application and further development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945894","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":"Integrated Network Pharmacology and Transcriptomics Analysis to Elucidate the Mechanism of Huoxue Tongluo Qiwei Decoction in the Treatment of Erectile Dysfunction in Spontaneously Hypertensive Rats through Angii-Activated Pkcε Pathway.","authors":"Junlong Feng, Sheng Deng, Bin Wang, Cong Zhao, Kali Zou, Haisong Li, Jisheng Wang","doi":"10.2174/0113862073330086241016115236","DOIUrl":"https://doi.org/10.2174/0113862073330086241016115236","url":null,"abstract":"<p><strong>Background and aim: </strong>As a classical formula to invigorate blood circulation, Huoxue Tongluo Qiwei Decoction (HTQD) can effectively treat hypertensive erectile dysfunction (ED), but its exact mechanism of action is not yet clear. The goal of this research was to explore the potential mechanism of HTQD in improving hypertensive erectile dysfunction in rats through transcriptomics, network pharmacology, and associated animal experimentations.</p><p><strong>Methods: </strong>The HTQD chemical constituents were screened using high-performance liquid chromatography- tandem mass spectrometry (HPLC-MS/MS). Furthermore, transcriptomics analysis was performed via mRNA sequencing to identify significantly differentially expressed proteins. Moreover, the key target proteins of HTQD in the treatment of hypertensive ED were screened by network pharmacology and transcriptomics. In addition, the endothelial cells of the corpus cavernosum were assessed using hematoxylin-eosin staining. The transcript and protein expressions were evaluated via western blotting and Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>The network pharmacology and transcriptome mRNA sequencing revealed that KCNE1 may be the target protein of HTQD in improving hypertensive ED. After HTQD treatment, the systolic and diastolic blood pressure (BP) of hypertensive rats decreased, the number of erections increased, and the pathological structure of the penis was improved. Moreover, HTQD downregulated the protein and mRNA expression of AngII, AT1R, DAG, and PKCε, whereas it upregulated the transcript and protein expression of KCNE1.</p><p><strong>Conclusion: </strong>HTQD may activate the PKCε pathway through AngII, inhibit the expression of KCNE1 protein, relax vascular smooth muscles, and improve erectile function.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945901","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":"Therapeutic Bioactivities and Chemical Composition Analysis of Rhizome Oleoresin of Hedychium coronarium Collected from Uttarakhand, India.","authors":"Sushila Arya, Ravendra Kumar, Om Prakash, Mamta Latwal, Ganesh Pandey, Satya Kumar, R M Srivastava, Suraj N Mali","doi":"10.2174/0113862073327439241119113953","DOIUrl":"https://doi.org/10.2174/0113862073327439241119113953","url":null,"abstract":"<p><strong>Introduction: </strong>Hedychium coronarium J. König, from the Zingiberaceae family, is a rhizomatous herb used in Ayurvedic medicine for its febrifuge, anti-rheumatic, and anthelmintic properties.</p><p><strong>Method: </strong>This study characterizes the chemical diversity and biological activities of H. coronarium oleoresins collected from four locations in Uttarakhand: Pantnagar (HCPNOR), Bageshwar (HCBOR), Nainital (HCNOR) and Pithoragarh (HCPOR). GC-MS analysis identified key constituents, including n-Hexadecanoic acid (8.3-9.8%), photocitral B (4.8- 27.6%), (Z)-9- eicosenoic acid (0.7-6.5%), α-pinene (2.5-3.5%) and trans-13-octadecenoic acid (7.5%). Heat map clustering, Venn diagrams, and PCA revealed compositional variations.</p><p><strong>Result: </strong>The oleoresins showed potent nematicidal, insecticidal, herbicidal, and antifungal activities against Meloidogyne incognita, Spodoptera litura, Raphanus raphanistrum subsp. sativus, Fusarium oxysporum, and Curvularia lunata.</p><p><strong>Conclusion: </strong>These findings highlight the potential of H. coronarium oleoresins for pest and pathogen management, with chemical variation driven by environmental factors.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022477","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":"Investigation of the Potential Pharmacological Substance Basis and Mechanism of Action of Xuantu Granules in Treating Diabetic Kidney Disease Based on UHPLC-Q-Exactive-HRMS and Bioinformatics.","authors":"Jingna Fan, Chang Kong, Bin Yu, Rong Wang, Zhenqiang Qi","doi":"10.2174/0113862073364424241202111833","DOIUrl":"https://doi.org/10.2174/0113862073364424241202111833","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to analyze and identify the main chemical components and blood-absorbed components of Xuantu Granules and predict their pharmacological substance basis and mechanism in the treatment of DKD.</p><p><strong>Methods: </strong>A DKD rat model was established by feeding SD rats a high-fat and high-sugar diet and administering intraperitoneal injections of streptozotocin (STZ). The therapeutic effect of Xuantu granules was evaluated. Drug-containing serum was prepared after gavage, and the major chemical components of Xuantu Granules and the drug-containing serum were detected using UHPLC-Q-Exactive-HRMS. Blood-absorbed components were identified based on retention time, mass-to-charge ratio, and MS/MS spectrum. Blood-absorbed components' target proteins were searched using the CTD, SwissTarget, BindingDB, and TargetNet databases. DKD disease target genes were screened from the GEO database using WGCNA. A \"bioactive blood-absorbed component-target-disease\" PPI network was constructed using Cytoscape software, and the key clustering subnetworks were identified by MCODE plugin. GO functional analysis and KEGG pathway enrichment analysis were performed on subnetworks.</p><p><strong>Results: </strong>Xuantu Granules lowered fasting blood glucose, improved renal function, reduced proteinuria, and improved renal tissue pathological changes in DKD rats. 36 chemical components were identified, among which 12 compounds, including β -Carboline-1-propionic acid, Morin, Afzelin, Schizandrin, Gomisin A were identified as blood-absorbed components. Bioinformatics analysis indicated that AKT1, TNF, TP53, IL6, SRC, IL1B, EGFR, JUN, BCL2, and CASP3 might be the main therapeutic targets. The involved pathways included the IL-17 signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications and so on.</p><p><strong>Conclusion: </strong>Xuantu Granules may exert therapeutic effects on DKD through multiple targets and pathways.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945246","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":"Unveiling the Interplay between Dopamine-like Molecules and Β-Amyloid Peptide: A Combined Molecular Dynamic and DFT Approach.","authors":"Mohammad Erfan Zand, Mohammad Reza Bozorgmehr, Mohammad Momen Heravi, S Ali Beyramabadi","doi":"10.2174/0113862073331831241015103725","DOIUrl":"https://doi.org/10.2174/0113862073331831241015103725","url":null,"abstract":"<p><strong>Aims: </strong>This study aims explore the impact of catechol, dopamine, and L-DOPA on the stability and toxicity of β-amyloid peptides, which play a key role in the neurodegenerative process of Alzheimer's disease, to assess their potential as therapeutic agents.</p><p><strong>Background: </strong>Alzheimer's disease is marked by the aggregation of β-amyloid peptides, which contribute to neurodegeneration. Exploring how various compounds interact with β-amyloid peptides can offer valuable insights into potential therapeutic strategies.</p><p><strong>Objective: </strong>The objective of this research is to explore the interaction mechanisms of catechol, dopamine, and L-DOPA with β-amyloid peptides and assess their impact on peptide stability and aggregation.</p><p><strong>Method: </strong>This study employs molecular dynamics simulations combined with density functional theory to investigate the interactions between β-amyloid and the three compounds. It evaluates changes in peptide stability and salt bridge lengths and performs electronic structure analyses using the Electron Localization Function (ELF) and Harmonic Oscillator Model of Aromaticity (HOMA).</p><p><strong>Results: </strong>The findings reveal that β-amyloid stability decreases significantly when interacting with dopamine and L-DOPA compared to catechol. All three compounds inhibit β-amyloid, with dopamine and L-DOPA showing stronger effects. Catechol primarily interacts through hydrophobic interactions, while dopamine and L-DOPA also form hydrogen bonds with β-amyloid. Electronic structure analysis shows catechol has higher electron localization and anti-aromatic character, affecting its interactions differently than dopamine and L-DOPA. A decrease in the HOMO-LUMO gap from catechol to L-DOPA to dopamine indicates increasing reactivity towards β-amyloid.</p><p><strong>Conclusion: </strong>Dopamine and L-DOPA more effectively disrupt β-amyloid aggregation than catechol, likely due to additional hydrogen bonding and increased electronic reactivity. These insights are crucial for developing therapeutic strategies targeting β-amyloid aggregation in Alzheimer's disease, emphasizing the importance of molecular interactions in modulating peptide stability and toxicity. The study also provides a comparative analysis of the electronic properties and interaction dynamics of the compounds, which can guide future research in the design of β-amyloid inhibitors. The utilization of advanced simulation techniques underscores the potential for computational methods in understanding complex biological interactions and developing novel therapeutic agents. Furthermore, the insights into the differential effects of hydrophobic interactions versus hydrogen bonding offer valuable information for the synthesis of new compounds aimed at mitigating β-amyloid toxicity.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930817","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":"Ferroptosis-related Biotargets and Network Mechanisms of Maslinic Acid Against Myocardial Ischemia-reperfusion Injury: An Integrated Bioinformatic and Experimental Approach.","authors":"Qi Li, Guiyuan He, Rujie Zheng, Chunlei Liu, Che Wang, Zhihao Liu, Zhuqing Li, Chengzhi Lu","doi":"10.2174/0113862073354768241217162514","DOIUrl":"https://doi.org/10.2174/0113862073354768241217162514","url":null,"abstract":"<p><strong>Background: </strong>Maslinic acid (MA), a pentacyclic triterpenoid compound derived from leaves and fruits of Olea europaea, bears multi-pharmacological properties. Our previous studies found that MA exerted a cardioprotective effect by modulating oxidative stress, inflammation, and apoptosis during myocardial ischemia-reperfusion injury (MIRI). Nevertheless, data regarding the anti-ferroptosis effects of MA on MI/RI remains unidentified.</p><p><strong>Aim of the study: </strong>This study aimed to explore the effects of MA on ferroptosis induced by MI/RI, with a focus on elucidating the underlying mechanisms through an integrated approach of network pharmacology and experimental validation.</p><p><strong>Materials and methods: </strong>Several public databases and a protein-protein interaction (PPI) network were used to identify the core targets shared by MI/RI, ferroptosis, and MA. The molecular function, cell component, biological process, and potential signaling pathways of core genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Subsequently, molecular docking and in vitro experiments were carried out to further validate network pharmacology results.</p><p><strong>Results: </strong>A total of 21 unique intersection genes were obtained as potential targets of MA in treating MI/RI-induced ferroptosis. The 10 hub genes with the highest interaction scores were identified from PPI analysis. GO and KEGG enrichment showed the contribution of the core genes to pharmacological actions and mechanisms in MA treatment of MI/RI, especially the ferroptosis-related signaling pathways. Additionally, MA docked well with ranked core targets, including MAPK, MTOR, STAT3, PTGS2, and MDM2. Subsequently, in vitro experiments revealed that MA notably alleviated oxidative damage, reduced ferrous iron overload and ferroptosis, and regulated the expression of ferroptosis-related genes (GPX4, PTGS2, and ACSL4) in erastin-induced H9c2 cells. Meanwhile, MA could significantly reduce phosphorylation of MAPK (ERK1/2) levels in H9c2 cells.</p><p><strong>Conclusion: </strong>By utilizing network pharmacology and experimental data, our study revealed the correlation between MA and ferroptosis following MI/RI, and concluded that MA might protect against MI/RI by reducing ferroptosis through the ERK1/2 signaling pathway. This finding offered fresh insights into the pharmacological mechanisms of MA against MI/RI.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930569","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":"Verification of Qianlong Shutong Formula in the Treatment of Benign Prostatic Hyperplasia.","authors":"Ze-Chao Zhang, Min Zhu, Shu-Ping Huang, Zhi-Feng Wei, Yu Chen, Chang-Jie Shang","doi":"10.2174/0113862073336172241220182220","DOIUrl":"https://doi.org/10.2174/0113862073336172241220182220","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the mechanisms through which Qianlong Shutong Formula (QLSTF) exerts its effects on the management of benign prostatic hyperplasia (BPH).</p><p><strong>Background: </strong>BPH is a prevalent condition among older men and poses significant management challenges due to the limited effectiveness and potential side effects associated with current treatment options. QLSTF, a traditional Chinese medicine, has been utilized in the treatment of BPH; however, its mechanism of action remains inadequately understood.</p><p><strong>Objective: </strong>This study aimed to identify potential therapeutic targets of QLSTF for the management of BPH through the application of network pharmacology and subsequent experimental validation.</p><p><strong>Methods: </strong>QLSTF compounds were identified utilizing liquid chromatography-mass spectrometry (LC-MS). Potential targets of QLSTF, as well as BPH-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro and in vivo experiments were conducted to further verify the findings.</p><p><strong>Results: </strong>A total of 52 bioactive ingredients of QLSTF and 760 QLSTF-BPH-related targets were screened. Bioinformatics analysis revealed that Afzelin, Ononin, Glycitin, Emodin and Erythritol may be potential candidate agents. AKT1, SRC, STAT3, GRB2, HRAS, MAPK3, PIK3CA, PIK3R1, HSP90AA1, and EP300 could become potential therapeutic targets. PI3KAKT signaling pathway might play an important role in QLSTF against BPH. Moreover, molecular docking suggested that Afzelin, Ononin, Glycitin, Emodin, and Erythritol combined well with AKT1, SRC, STAT3, HRAS, MAPK3, PIK3CA, and PIK3R1, respectively. In vitro and in vivo experiments showed that QLSTF could inhibit the proliferation of cells, as well as the PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology strategy and molecular docking.</p><p><strong>Conclusions: </strong>QLSTF may exert its therapeutic effects on BPH by modulating the PI3K/AKT signaling pathway and inhibiting glandular hyperplasia. This study offers valuable insights into the therapeutic targets of QLSTF in the management of BPH.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930818","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":"Nanomaterials for Temporomandibular Joint Osteoarthritis Therapy: A Mini-Review.","authors":"Lulu Chen, Chengcheng Liao","doi":"10.2174/0113862073339608241214053500","DOIUrl":"https://doi.org/10.2174/0113862073339608241214053500","url":null,"abstract":"<p><p>Osteoarthritis, particularly temporomandibular joint (TMJ) osteoarthritis (OA), poses significant challenges in diagnosis and treatment. Recent studies suggest that nanomaterials hold considerable promise in treating TMJ-OA, showing validated efficacy in animal models. However, further research is required to ensure their long-term safety within the TMJ-OA environment. Nanomaterials can facilitate drug delivery and encapsulate functional cells and extracellular vesicles, offering new avenues for exploration. This paper reviews the current research status of nanomaterials in TMJ-OA treatment, including drug delivery, anti-inflammatory, lubricating and buffering, antioxidant, tissue regeneration, scaffold, and stimuli-responsive nanomaterials. Additionally, the paper explores the development and future prospects of nanomaterials in TMJOA treatment, highlighting their unique contributions and aiming to provide new perspectives and solutions for unexplored areas.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930816","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}