Current pharmaceutical design最新文献

{"title":"Neuroprotective Effects of Thymol-Loaded Selenium Nanoparticles Against 6-OHDA-Induced Apoptosis and Oxidative Stress in an In Vitro Parkinson's Disease Model.","authors":"Farzaneh Abbasinezhad-Moud, Matin Shirazinia, Raheleh Mirzabeyki, Elham Einafshar, Mohaddeseh Sadat Alavi, Sayeh Shaban, Elaheh Gheibi, Afsane Bahrami","doi":"10.2174/0113816128380006250630103711","DOIUrl":"https://doi.org/10.2174/0113816128380006250630103711","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra, leading to progressive motor dysfunction. There are still limited diseasemodifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol, both in its free form and when loaded onto selenium nanoparticles (SeNPs), in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells.</p><p><strong>Method: </strong>SeNPs were synthesized using a chemical reduction method with ascorbic acid, achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium, which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical, with a mean size of 135.7 nm and a negative surface charge.</p><p><strong>Results: </strong>Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore, Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins, which were elevated by 6-OHDA, compared to thymol alone.</p><p><strong>Discussion: </strong>Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity, as evidenced by a significant reduction in ROS levels, along with its ability to inhibit apoptosis and modulate cell cycle progression.</p><p><strong>Conclusions: </strong>Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however, further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658647","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":"Development and Optimization of Polyelectrolyte Complex Stabilized Piperine Adjuvant Simvastatin Nanoformulations for Improved Therapeutic Effect.","authors":"Shristy Verma, Sonali Sundram, Mohammad Yusuf, Musarrat Husain Warsi, Rishabha Malviya","doi":"10.2174/0113816128382527250625165648","DOIUrl":"https://doi.org/10.2174/0113816128382527250625165648","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to prepare polyelectrolyte complex stabilized piperine adjuvant simvastatin nanoformulations and evaluate the antimicrobial effect. Simvastatin has antimicrobial properties but low therapeutic efficacy due to rapid metabolism, with only 12% oral bioavailability. Piperine, a CYP3A4 inhibitor, enhances bioavailability by inhibiting drug-metabolizing enzymes. This study developed chitosan-neem gum polyelectrolyte complex (Ch-NG PEC) nanoparticles combining piperine and simvastatin and evaluated their antimicrobial efficacy compared to simvastatin alone.</p><p><strong>Methods: </strong>A flower-shaped nanoparticles of piperine adjuvant simvastatin were prepared by using chitosan (Ch)-neem gum (NG) as a polyelectrolyte complex (PEC) forming agent, and the anti-microbial effect of nanoformulations with and without piperine was evaluated. A solvent-anti-solvent method was used to form the nanoparticles, and a 32-factorial design was employed to analyze the impact of chitosan and neem gum concentration on the size of the nanoparticles and entrapment efficiency of simvastatin and piperine followed by their release profile and kinetics.</p><p><strong>Results: </strong>Nanoparticles showed high drug entrapment efficiency (simvastatin: 96.4-99.7%, piperine: 64.8- 99.4%) with sizes ranging from 341.3-629.1 nm. Drug release exceeded 50% in 3 hours and 99% in 8 hours, following Hixon-Crowell and Baker's Lonsdale models. Antimicrobial assays revealed activity against Staphylococcus aureus but not Candida albicans. The results of the anti-microbial assay indicated that the PECbased NPs stabilized piperine adjuvant simvastatin showed anti-microbial activity against Staphylococcus aureus but did not exhibit anti-fungal activity against Candida albicans.</p><p><strong>Conclusion: </strong>Piperine-adjuvant simvastatin Ch-NG-PEC nanoparticles demonstrate potential as a dualtreatment agent for hypercholesterolemia and bacterial infections.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648793","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 Targeted Approaches to Combat Drug Resistance in Cancer Chemotherapy.","authors":"Siddharth, Siddhant, Salahuddin, Avijit Mazumder, Rajnish Kumar, Abhijit Debnath","doi":"10.2174/0113816128380235250627143945","DOIUrl":"https://doi.org/10.2174/0113816128380235250627143945","url":null,"abstract":"<p><p>Despite significant advancements in medical science, cancer continues to be a major cause of morbidity and mortality worldwide. A key factor contributing to this persistent burden is the emergence of resistance to conventional therapeutic modalities, including chemotherapy, radiation therapy, and surgery. This phenomenon of drug resistance significantly hampers the efficacy of these treatments, leading to therapeutic failure and poor clinical outcomes. A detailed understanding of the molecular and cellular mechanisms underlying drug resistance is crucial for devising targeted strategies to overcome these barriers. In this review, we aim to critically assess and highlight various approaches that can effectively reduce chemotherapy resistance, with the goal of improving the therapeutic efficacy of chemotherapy and enhancing overall patient survival.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636462","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 Developments in Vesicular Nanocarriers for Targeted Drug Delivery in Breast Cancer.","authors":"Shreastha Gautam, Priya Jindal, Sachin Joshi, Rashmi Maurya, Preeti Patel, Ghanshyam Das Gupta, Balak Das Kurmi","doi":"10.2174/0113816128385024250625212516","DOIUrl":"https://doi.org/10.2174/0113816128385024250625212516","url":null,"abstract":"<p><p>Breast cancer remains one of the most challenging malignancies worldwide due to its heterogeneity, which affects tumor behavior, progression, and treatment response. The complexity of breast cancer necessitates innovative therapeutic strategies to improve treatment outcomes. This review explores the potential of vesicular nanocarriers, including liposomes, niosomes, ethosomes, polymerosomes, phytosomes, and transferosomes, in enhancing breast cancer treatment efficacy through targeted drug delivery. A detailed analysis of recent progress in the functionalization and application of vesicular nanocarriers is discussed, highlighting their contribution to enhancing pharmacokinetics, drug solubility, and targeted delivery. Both passive and active targeting strategies were assessed for their ability to enhance tumor-specific drug accumulation. Vesicular nanocarriers offer significant advantages, including reduced systemic toxicity, improved drug bioavailability, and precise delivery to cancer cells. Passive targeting utilizes the enhanced permeation and retention effect for tumor accumulation, while active targeting employs surface modifications with antibodies, aptamers, or peptides to enhance specificity. The integration of vesicular nanocarriers in breast cancer therapy presents a promising strategy for more effective and personalized treatment approaches. Their ability to optimize drug delivery and minimize off-target effects highlights their potential to revolutionize breast cancer treatment.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636461","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":"miRNA in Diagnosis and Therapeutics of Tuberculosis: Importance in Latent and Brain Associated Pathologies.","authors":"Parul Gupta, Ravindra Kumar, Rituraj Niranjan","doi":"10.2174/0113816128362931250619113617","DOIUrl":"https://doi.org/10.2174/0113816128362931250619113617","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are the regulators of gene expression and several cellular processes related to the immune system. miRNAs during tuberculosis (TB) infection are considered regulatory factors for the host immune system. Mycobacterium tuberculosis has a great ability to survive and multiply in phagocytic cells, which makes it difficult to treat. It can replicate through various cellular pathways. To establish the infection in the host cell, m. tuberculosis changes in the miRNA expression and increases survival capacity with high infectivity. miRNAs are widely used as biomarkers and therapeutic agents for tuberculosis. During m. tuberculosis infection, altered miRNA expressions can cause the progression of the disease and discriminate between latent and active TB infection. Due to their active involvement in disease progression, miRNAs may be utilized as potential biomarkers. Furthermore, the involvement of miRNA in autophagy and apoptosis modulation against m. highlights its potential for host-directed therapy. In this review article, we attempt to summarize the expression and role of various miRNAs in TB as immune modulators, differential activators between different phases of TB, including neuronal dysfunction in the brain, and as therapeutic targets and diagnostic tools against TB.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636460","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 Molecular Modeling Approach for Potential PTGS2 Inhibitors against Rheumatoid Arthritis.","authors":"Huda Abbasi, Maria Sharif, Peter John, Attya Bhatti","doi":"10.2174/0113816128370525250407164738","DOIUrl":"https://doi.org/10.2174/0113816128370525250407164738","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However, the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity, necessitating the exploration of safer alternatives.</p><p><strong>Objective: </strong>This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.</p><p><strong>Methods: </strong>The therapeutic potential of C. angustifolia was evaluated through antioxidant and antiinflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption, distribution, metabolism, excretion, and toxicity), network pharmacology, and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.</p><p><strong>Results: </strong>C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets, with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [1,3] dioxol-5- yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol, respectively) predicting its stable interaction.</p><p><strong>Conclusion: </strong>C. angustifolia compounds present a significant potential as PTGS2 inhibitors, warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607750","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":"Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease.","authors":"Emir Muzurović, Martin Haluzik, Ludek Horváth, Bogdan Vlacho, Didac Mauricio","doi":"10.2174/0113816128378484250619080753","DOIUrl":"https://doi.org/10.2174/0113816128378484250619080753","url":null,"abstract":"<p><p>Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus (T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However, the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/ fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM, and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607749","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":"Neuroprotective Effects of Eugenol in Alzheimer's Disease: Mitigating Oxidative Stress, Inflammation and Amyloid Plaques.","authors":"Aniket Kakkar, Harpreet Singh, Amit Anand, Hitesh Chopra, Arun Kumar Mishra","doi":"10.2174/0113816128373290250620054118","DOIUrl":"https://doi.org/10.2174/0113816128373290250620054118","url":null,"abstract":"<p><p>Eugenol, a phenolic phytochemical found in many medicinal plants, exhibits various pharmacological properties, including analgesic, antipyretic, antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, and anaesthetic effects. It has shown potential in addressing neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and motor neuron disease, which are primarily caused by mechanisms such as apoptosis, protein accumulation, aging, and oxidative stress within the central nervous system (CNS). This review explores the mechanisms through which eugenol may influence AD. Eugenol appears to counter oxidative stress, reduce inflammation, and prevent amyloid beta (Aβ) plaque accumulation, suggesting it could delay the onset or progression of AD. However, more research is required to establish its safety and effectiveness in treating or preventing this disease.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599652","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":"Stem Cell Nanotechnology Applications as Drug Delivery Systems for Cancer Therapy: A New Era in Targeted Treatment.","authors":"Gyas Khan","doi":"10.2174/0113816128379044250620122425","DOIUrl":"https://doi.org/10.2174/0113816128379044250620122425","url":null,"abstract":"<p><p>Cancer is still one of the most serious and life-threatening diseases in humans, and the conventional chemotherapies, radiation treatments, and surgical methods have yet to provide an effective resolution due to some drawbacks concerning drug resistance, general toxicity, and poor targeting to tumor sites. To surmount these challenges, some innovative approaches are under exploration; hence, the emergence of more promising solutions in the format of nanotechnology that combine with stem cell (SC)-based drug delivery systems (DDS). Its advantages include autonomous proliferative potential and the ability to clonally generate various cell types, leading to malignant transformation. Additionally, they possess an innate ability to migrate toward tumor sites, making them highly effective vectors for targeted DDS. The integration of nanotechnology with SCs offers several benefits, such as controlled release of therapeutic molecules, improved bioavailability, and reduced systemic toxicity. These advantages may provide the opportunity to improve cancer therapy with fewer side effects than those resulting from conventional treatments. This review has focused on the emerging role of SC-nanotechnology-based DDS as a new era in targeted cancer treatment and has emphasized enhancing therapeutic outcomes with a more precise approach to cancer therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599681","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 Potential of Cannabis as a Sustainable Antimicrobial Approach: What to Foreknow?","authors":"Natália Cruz-Martins, Latifa Bouissane","doi":"10.2174/0113816128406019250702060456","DOIUrl":"https://doi.org/10.2174/0113816128406019250702060456","url":null,"abstract":"","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599682","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}