Current pharmaceutical design最新文献

{"title":"Design, Molecular Docking, In Vitro and In Vivo Evaluation of Dimenhydrinate-Cyclodextrin Complex for Fast-Disintegrating Tablet.","authors":"Randa Khalid Samara, Rana M F Sammour, Veronique Seidel, Bazigha K Abdul Rasool","doi":"10.2174/0113816128398157250610113637","DOIUrl":"https://doi.org/10.2174/0113816128398157250610113637","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to formulate and evaluate dimenhydrinate (DMH) as fastdisintegrating tablets (FDTs) complexed with β-cyclodextrin (β-CD) to enhance its solubility, dissolution profile, and pharmacological performance.</p><p><strong>Methods: </strong>A DMH:β-CD inclusion complex was prepared at a 1:1 molar ratio using the kneading method. Characterization was performed through phase solubility studies, FTIR analysis, molecular docking, and in vitro dissolution testing. FDTs were developed using various superdisintegrants and assessed for quality attributes of a tablet, including hardness, friability, wetting time, water absorption ratio, and drug content.</p><p><strong>Results: </strong>Phase solubility and FTIR analyses confirmed the formation of a stable DMH:β-CD complex. Molecular docking indicated a binding affinity of -4.2 kcal/mol between β-CD and diphenhydramine. Among the FDT formulations, CP3 containing 9% crospovidone showed the best performance, with a disintegration time of 4.3 seconds and the highest drug release rate. In vivo pharmacological tests demonstrated enhanced sedative and antiemetic activities of the optimized FDTs compared to conventional DMH formulations.</p><p><strong>Discussion: </strong>The findings suggest that cyclodextrin-based complexation combined with orodispersible tablet technology can significantly enhance DMH's pharmacological efficacy and patient compliance. However, additional investigations on long-term stability, pharmacokinetics, and clinical scalability are warranted.</p><p><strong>Conclusion: </strong>The DMH:β-CD FDTs developed in this study offer promising improvements in solubility, dissolution, and therapeutic performance, indicating their potential for better clinical outcomes and patient acceptability.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316072","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":"An in silico Approach for Identification of Novel Natural Selective ALR2 Inhibitors from Cynomorium songaricum for Treating Diabetic Complications.","authors":"Khalid Alshaghdali, Munazzah Tasleem, Talal Alharazi, Tolgahan Acar, Gamal Mohamed Elawad Ahmed, Emad Abboh, Kamal Yassin, Amre Nasr, Mohd Saeed, Dharmendra Kumar Yadav, Amir Saeed","doi":"10.2174/0113816128372035250526145207","DOIUrl":"https://doi.org/10.2174/0113816128372035250526145207","url":null,"abstract":"<p><strong>Introduction: </strong>Aldose reductase-2 (ALR2) is a key enzyme in the polyol pathway whose overexpression is implicated in several diabetic complications, including neuropathy, nephropathy, retinopathy, and atherosclerotic plaque formation. Under hyperglycemic conditions, the intracellular accumulation of sorbitol and the depletion of NADPH lead to osmotic imbalance and oxidative stress, driven by the formation of reactive oxygen species and advanced glycation end products. Although various ALR2 inhibitors have been developed, their clinical application has been hampered by nonselective inhibition of both ALR2 and the homologous enzyme ALR1.</p><p><strong>Method: </strong>In this study, we employed a comprehensive in silico approach to evaluate the inhibitory potential of natural compounds from Cynomorium songaricum against ALR2. Our workflow integrated with ADMET, molecular docking with scoring function and glide XP, molecular dynamics (MD) simulations, PCA, FEL, and MM/GBSA. Through this analysis, four natural compounds of C. songaricum (Compound Name: p-Coumaric acid, Vanillic acid, 4-Oxoniobenzoate, and Phloroglucinol) displayed significant bonds formation including hydrogen and hydrophobic bonds with the target protein.</p><p><strong>Results: </strong>These bonds exhibited the ligand stability. Further, the MD simulation analysis, followed by postsimulation analysis, verified the dynamic stability of these four natural compounds and compared them with the native ligand of the target protein. These natural compounds exhibit particularly stable binding within the ALR2 selectivity pocket, demonstrating an inhibitory effect over ALR1 when compared with the reference inhibitor, Epalrestat.</p><p><strong>Conclusion: </strong>These promising in silico findings suggest that CID: 8468 and CID: 135 merit further evaluation through in vitro, in vivo, and clinical studies as potential selective inhibitors for the treatment of diabetic complications.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282801","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":"Astragalus Injection Modulates the Pharmacokinetics of Doxorubicin and CYP450 Enzymes.","authors":"Wenjun Shi, Tian Liu, Kaihe Wang, Leixin Mu, Li Ji, Yanling Li, Yi Zhang, Qun Ma","doi":"10.2174/0113816128362829250527023843","DOIUrl":"https://doi.org/10.2174/0113816128362829250527023843","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is a widely used anthracycline antibiotic for the treatment of breast cancer, liver cancer, lymphoma, and other malignant tumors. However, its clinical application is limited by the side effects and drug resistance. Astragalus injection has been combined with DOX in the treatment of cancer, which improves the curative effect and reduces drug resistance. This study investigated the interaction between DOX and Astragalus injection and elucidated the potential mechanism.</p><p><strong>Methods: </strong>The pharmacokinetics of DOX injection (7 mg/kg, intraperitoneal injection) with or without Astragalus injection (4.25 mL/kg/day for 14 days, intraperitoneal injection) were investigated in plasma from male Sprague-Dawley rats (n = 6) by UPLC-MS/MS. The group without the Astragalus injection was set as the control group. Additionally, the effects of Astragalus injection on CYP450 enzyme activities were assessed using a rat liver microsome incubation system with cocktail probe drugs.</p><p><strong>Results: </strong>Astragalus injection significantly increased the Cmax (2090.01 ± 99.60 vs. 5262.77 ± 111.15 ng/mL) and AUC0-t (1190.23 ± 104.43 vs. 3777.27 ± 130.55 μg/L × h) and prolonged the t1/2α (0.09 ± 0.02 vs. 0.14 ± 0.04 h) of DOX. Astragalus injection significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4, and enhanced the activity of CYP2D1 with a metabolic elimination rate of 30.11 ± 2.67% vs. 19.66 ± 3.41%, 35.95 ± 2.57% vs. 23.26 ± 3.57%, 13.43 ± 2.56% vs. 9.06 ± 2.51%, 47.90 ± 6.30% vs. 25.87 ± 2.55%, 17.62 ± 1.49% vs. 24.12 ± 2.91%, respectively (p < 0.05).</p><p><strong>Conclusion: </strong>The co-administration of DOX and Astragalus injection alters the systemic exposure of DOX by affecting the metabolism of DOX and the activity of CYP450 enzymes. These findings highlight the importance of drug-drug interactions when combining Astragalus injection with DOX and provide a basis for optimizing combination therapies to address DOX resistance and toxicity.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224638","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":"Revolutionizing Antibiotic Delivery: Harnessing 3D-Printing Technology to Combat Bacterial Resistance.","authors":"Shubham Singh, Mohit Kumar, Deeksha Choudhary, Dikshant -, Devesh Kumar, Shruti Chopra, Amit Bhatia","doi":"10.2174/0113816128365632250524160128","DOIUrl":"https://doi.org/10.2174/0113816128365632250524160128","url":null,"abstract":"<p><p>Antibiotic resistance poses a significant threat to public health, rendering many life-saving medications ineffective as pathogenic microorganisms develop resistance spontaneously. This results in infections that are difficult to treat, with limited or no treatment options. Traditionally, addressing this challenge involves developing new pharmaceuticals, a lengthy and costly process. However, a more efficient approach lies in improving drug delivery methods, which can be quicker and more economical. In recent years, 3D printing technology has emerged as a groundbreaking, industry-accepted technique that enables the affordable, simple, and rapid manufacturing of pharmaceuticals. This technology supports iterative design-build-test cycles, facilitating the development of a wide range of products, from simple 3D-printed tablets to complex medical devices, tailored for diverse applications. This article explores innovative strategies in the search for novel antibiotics, the development of more effective preventative measures, and, crucially, a deeper understanding of the ecology of antibiotics and antibiotic resistance. It provides an overview of these issues' historical and current status, emphasizing the potential of 3D printing to address antibiotic resistance. Additionally, it discusses how to expand conceptual frameworks in response to recent advancements in chemotherapy, antimicrobials, and antibiotic resistance. The article highlights various notable efforts in utilizing 3D printing to develop antimicrobial dosage forms and medical devices, offering insights into future possibilities.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224639","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":"Unraveling the Pivotal Role of Nanovesicle Drug Delivery Systems in Colorectal Cancer: A New Paradigm in Therapeutics.","authors":"Sukhbir Singh, Himanshu Mehendiratta, Neelam Sharma, Ladli Kishore","doi":"10.2174/0113816128362419250523061958","DOIUrl":"https://doi.org/10.2174/0113816128362419250523061958","url":null,"abstract":"<p><p>Colorectal cancer is a highly prevalent gastrointestinal malignancy leading to mortality. The prolonged efficacy of chemotherapeutic medications has been hindered by their limited capacity to reach the intended target, their lack of specificity in targeting tumors, their non-specific dispersion throughout the body and limited availability at the tumor location, and their undesired adverse effects. Targeted drug delivery to the colon enhances drug concentration at the desired location, resulting in a reduced dosage requirement and consequently, fewer side effects. This review article provides a thorough discussion of the numerous pathways that may cause colorectal cancer. The concept of drug targeting in colorectal cancer using nanovesicles has been addressed in detail in this article. This can be accomplished either by passive targeting or active targeting through receptor-ligand interaction by attaching certain active targeting moieties, such as folic acid, epidermal growth factor receptor, GE-11 peptide, EpCAM aptamer, and transferrin, over the surface of nanovesicle. This review showcases applications of nanovesicle systems, such as liposomes, phytosomes, polymeric micelles, niosomes, cubosomes, emulsomes, polymersomes and lipopolymersomes in drug delivery for the management of colorectal cancer. The nanovesicle systems have significant potential in managing colorectal cancer and overcoming the challenges encountered with current therapy methods.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207916","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":"Unlocking the Enigmas of Plasmodium Aspartyl Protease in Antimalarial Therapy: Flap Region Dynamics and Enzyme Repression of Non-Food Vacuole Using Molecular Dynamics Simulations.","authors":"Ransford Oduro Kumi, Mahmoud E S Soliman","doi":"10.2174/0113816128288035240130102943","DOIUrl":"https://doi.org/10.2174/0113816128288035240130102943","url":null,"abstract":"<p><strong>Introduction: </strong>Plasmepsin X (PMX) is a crucial aspartyl protease that prevents malaria parasite invasion and egresses into erythrocytes, making it a potential multiple-stage therapeutic target.</p><p><strong>Methods: </strong>Recent research has led to the identification of UCB7362, an orally active PMX inhibitor with experimental antimalarial efficiency. In this report, we investigate the binding mechanism of UCB736 to the nonfood vacuole PMX. Most importantly, the detailed molecular description of the binding mechanism of UCB7362 to PMX sites that are not fully explored in the literature. We also examined the influence of UCB7363 binding on the flap region dynamics of PMX, a crucial dynamic event needed for protease enzyme activity and significant impacts on drug binding.</p><p><strong>Results: </strong>Molecular dynamics simulations and binding affinity calculations were utilized in this work. Interestingly, the catalytic dyad (Asp266 and Asp456) was found to be the most contributing residues towards the binding of UCB7362, underscoring the significance of the pair in the catalytic activity of the enzyme. Post- MD analyses revealed that UCB7362 binding caused disruption in the \"twist motion\" of the protease and subsequently forced the flap regions to coil in to tightly wrap the inhibitor, reducing the surface area and creating a compact binding architecture for the ligand.</p><p><strong>Conclusion: </strong>Finally, we developed a pharmacophore model based on UCB7362 to offer recommendations for rational drug design of optimized antimalarial drug candidates.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207915","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":"Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.","authors":"Hawraa Ibrahim Alshakarchi, Hanieh Azari, Zuhair Muhammad Ali Jadoua, Nadhir Najim Abdullah Jafar, Yeganeh Khazaei, Ibrahim Saeed Gataa, Gordon A Ferns, Amir Avan","doi":"10.2174/0113816128341167250520063502","DOIUrl":"https://doi.org/10.2174/0113816128341167250520063502","url":null,"abstract":"<p><p>Cytochrome P450 (CYP 450) plays a pivotal role in the metabolism of a diverse range of agents, and its dysregulation can contribute to tumorigenesis, including tumor angiogenesis across various cancer types. This dysregulation may activate procarcinogenic xenobiotics and endogenous molecules while also inactivating anti-cancer drugs, resulting in drug resistance. The aim of this review is to demonstrate the potential and relevance of CYP inhibitors in the treatment of colorectal cancer (CRC). Several studies have documented the role of CYP enzymes in the metabolic rearrangements of various cancers through the mechanisms underlying metabolic rearrangements in CRC, including those related to glucose, fatty acids, cholesterol, and amino acids. Recent studies have focused on the targeting of metabolic mechanisms in CRC through the use of established CYP inhibitors, yielding varying degrees of success. Among these agents are clotrimazole (inhibitor of CYP24A1, 3A4, 2A6, and 2C8), KD-35 (CYP24A1 inhibitor), liarozole (CYP26A1 inhibitor), letrozole (CYP19A1 inhibitor), lopinavir/ritonavir and quercetin (CYP3A4 inhibitors), α-naphthoflavone and furanfylline (CYP1A1 inhibitors), as well as phenylpyrrole (a CYP1A2 and CYP2A6 inhibitor). Clinical studies investigating CYPs in cancer treatment have been reported in various cancers, including prostate, breast, pancreatic, hematological, lung, and salivary gland cancers, for purposes ranging from dose reduction and cost savings to enhance the efficacy of combined anti-cancer agents (CYP3A4, CYP3A4/5 and CYP1A2 inhibitors), and in addition, functioning as anti-cancer agents themselves (CYP17 inhibitors). Thus, these metabolizing enzymes reveal a complex interaction with cancer therapeutics, opening the door to novel strategies that go beyond conventional treatment paradigms. Harnessing CYP modulators could transform the treatment of CRC, offering more targeted and flexible options.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198373","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":"Recent Advancements in Stimuli-Responsive Polymeric Implants Fabricated via Additive Manufacturing: A Review.","authors":"Sachin Kothawade, Sudarshan Singh","doi":"10.2174/0113816128368347250515073105","DOIUrl":"https://doi.org/10.2174/0113816128368347250515073105","url":null,"abstract":"<p><p>This review discusses the latest progress in using smart polymeric materials for making medical implants with advanced three-dimensional (3D) and four-dimensional (4D) printing techniques. These smart polymers, also known as stimuli-responsive polymers, can change their properties when exposed to external triggers like temperature, pH, light, or magnetic fields. Integrating these materials with 3D/4D printing allows the creation of highly customizable and functional implants that can adapt to the body's environment. This means implants can now perform additional tasks, such as releasing drugs or changing shape when needed. The review covers different 3D/4D printing methods, the types of smart polymers available, and the benefits of using these materials in medical implants. It also addresses the challenges faced in developing these advanced implants, such as finding suitable materials that are safe for the body and ensuring precise manufacturing. The future prospects of these innovative implants are promising, with potential applications in personalized medicine and non-invasive treatments. This review aims to provide a detailed analysis of recent advancements in stimuli-responsive polymeric materials utilized in additive manufacturing of medical implants. The objective is to explore these materials' clinical implications, address the unique challenges in their development and fabrication, and outline their future potential in enhancing personalized and non-invasive medical treatments.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186753","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":"New Standards in the Treatment of Advanced Metastatic Melanoma: Immunotherapy and BRAF-Targeted Therapies as Emerging Paradigms.","authors":"Firas Kreidieh, Michael K Wong","doi":"10.2174/0113816128341628250519093548","DOIUrl":"https://doi.org/10.2174/0113816128341628250519093548","url":null,"abstract":"<p><p>Although cutaneous melanoma accounts for only about 2% of skin cancers, its rapid progression makes it an aggressive skin cancer with a high mortality rate. As of 2018, the SEER database estimated that the 5-year overall survival (OS) rate is 29.8% in patients with stage IV disease at diagnosis in the United States. Non-cutaneous melanoma, including mucosal and uveal subtypes, carries a generally worse prognosis. Once considered refractory to conventional treatments, such as chemotherapy and radiation therapy, the advent of immunotherapy, including immune checkpoint inhibitors (ICIs), vaccines, and tumor-infiltrating lymphocytes (TIL), and of targeted therapy over the past decade has resulted in dramatic improvements in melanoma. Importantly, ICIs have resulted in long-term remission for patients with melanoma, thus introducing the possibility of a cure for some patients with metastatic disease. These include antibodies against programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and lymphocyte activation gene-3 (LAG-3). In this review, we will provide an overview of metastatic melanoma while focusing on its current pharmacologic armamentarium, toxicities of treatment, including ICIs and targeted therapy, and its therapeutic clinical strategies. The therapeutic advances presented in this review serve as the foundation for an ever-expanding repertoire of innovative approaches. These include mRNA vaccines, oncolytic viruses, bispecific engagers, oral immunomodulators, and novel cytokines. Adoptive cellular strategies are evolving to TILS transduced with conditional gene expression cassettes, as well as non-T cell approaches involving dendritic cells and natural killer (NK) cells. Targeted therapy strategies have broadened to include upstream components of RAS, other MAP kinase pathways, and HDAC inhibitors, among others. All these new paradigms translate into increasingly complex decision-making for the treatment team, a burden that is more than offset by the tremendous benefit for melanoma patients. This is truly the beginning of a new era.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180212","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 into the Mechanisms of Paeoniae Radix Rubra in the Treatment of Venous Thrombosis Using Network Pharmacology, Bioinformatics, and Molecular Docking Techniques.","authors":"Shuo Xu, Ajiao Hou, Jiaxu Zhang, Jinhao Xue, Shiwen Gao, Hai Jiang, Liu Yang","doi":"10.2174/0113816128374345250521115849","DOIUrl":"https://doi.org/10.2174/0113816128374345250521115849","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the potential targets and mechanisms of Paeoniae Radix Rubra (PRR) in treating Venous Thrombosis (VTE) by employing network pharmacology, bioinformatics analysis, and molecular docking validation.</p><p><strong>Methods: </strong>Active components of PRR were identified via TCMSP. VTE-related genes were screened from GEO datasets, and WGCNA analyzed key modules. A Protein-Protein Interaction (PPI) network was constructed using Cytoscape, followed by immune infiltration analysis. Core targets were functionally annotated via GO and KEGG pathways. Molecular docking and molecular dynamics simulations validated interactions between PRR components and core targets.</p><p><strong>Results: </strong>A total of 30 active components of PRR and 21 potential targets for the treatment of VTE were identified. From the PPI network, 10 hub genes were screened. KEGG pathway enrichment analysis demonstrated that the target genes were significantly enriched in pathways, such as the cGMP-PKG signaling pathway, B cell receptor signaling pathway, Th1 and Th2 cell differentiation, and IL-17 signaling pathway. Molecular docking results revealed that MAPK1, NFATC1, and SELP all had good affinity with the screened active components. Among them, MAPK1 and beta-sitosterol exhibited the highest binding energy of -8.73 kcal/mol.</p><p><strong>Conclusion: </strong>Through this study, it was found that PRR may act on targets, such as MAPK1 and NFATC1, through components like beta-sitosterol and Stigmasterol. Among them, the complex (beta-sitosterol - MAPK1) may be the key active component that plays a role in treating VTE.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141753","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}