Future Pharmacology最新文献_第3页

Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights 解锁药用植物治疗阿尔茨海默病的潜力:临床前到临床试验的见解

Future Pharmacology Pub Date : 2023-11-13 DOI: 10.3390/futurepharmacol3040053

Kushagra Nagori, Kartik T. Nakhate, Krishna Yadav, None Ajazuddin, Madhulika Pradhan

{"title":"Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights","authors":"Kushagra Nagori, Kartik T. Nakhate, Krishna Yadav, None Ajazuddin, Madhulika Pradhan","doi":"10.3390/futurepharmacol3040053","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040053","url":null,"abstract":"Alzheimer’s disease (AD) is a progressive, multifactorial, and unremitting neurodegenerative disease characterized by memory loss, personality changes, and cognitive impairment. It has become more prevalent in recent years. Therefore, understanding the pathophysiology of AD and developing efficient therapeutic strategies are essential. Moreover, the progression of the disease is unaffected by the pharmaceutical approaches discovered to date. Additionally, the failure of over 200 potential drug candidates in clinical trials over the past decade suggests the complexity and difficulty of both the disease and its underlying causes. Therefore, research focused on medicinal plant-based natural products in the search for novel neuroprotective therapeutic candidates for AD is essential. Indeed, several scientific investigations have demonstrated the efficacy of many medicinal plants and their principal phytochemicals in the treatment of AD. This review article covered the pathophysiological mechanisms of AD, the necessity for natural products as anti-AD treatments, and the most recent preclinical studies revealing the function of neuroprotective medicinal plants and their bioactive compounds in the effective management of AD. In addition, the review also presents clinical trial data of promising anti-AD formulations/agents of plant origin. Revealing recent findings and highlighting the clinical trial data related to the development of new treatments for AD would promote further research in this field and pave the way for the development of more effective and safe treatments for this debilitating disease.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"142 29","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats 自发性高血压大鼠对他克莫司和霉酚酸酯的性别特异性反应

Future Pharmacology Pub Date : 2023-11-10 DOI: 10.3390/futurepharmacol3040052

Rodrigo Oscar Marañón, Mohadetheh Moulana

{"title":"Sex-Specific Responses to Tacrolimus and Mycophenolate Mofetil in Spontaneously Hypertensive Rats","authors":"Rodrigo Oscar Marañón, Mohadetheh Moulana","doi":"10.3390/futurepharmacol3040052","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040052","url":null,"abstract":"In recent decades, the roles of tacrolimus and mycophenolate mofetil (MMF) in hypertension have been under discussion. However, the question of whether there are sex-specific responses to these agents has not received enough attention. Aim: To evaluate sex-specific differences in the responses to tacrolimus and mycophenolate mofetil in female (F) and male (M) spontaneously hypertensive rats (SHRs) and evaluate whether T cells contribute to mean arterial pressure (MAP) changes. Methods: Male and female SHRs received either tacrolimus or MMF for 14 days. The rats were implanted with radiotelemeters. MAP was measured chronically; then, circulating and renal infiltrated CD4+, CD8+, T helper 17 (Th17), and T regulatory (Treg) cells were quantified using flow cytometry. Key Findings: Tacrolimus increased MAP only in males, and it decreased CD4+ and CD8+ T cells in both males and females (p < 0.05). The tacrolimus-induced reduction of renal CD4+ and Treg cells was more profound in males. MMF reduced MAP and circulating and renal CD4+ and CD8+ T cells in the male and female rats. MMF also decreased Th17 and Treg cells in both sexes, but the decrease in Th17 was higher in males (p < 0.05) and the reduction in Treg cells was higher in females (p < 0.05). Our findings indicate that the effects of tacrolimus and MMF on renal T cell subsets are sex-specific. Significance: Targeting T cells in hypertension using therapeutic agents may have different effects on men and women; so, the management of hypertension and post-transplant hypertension using these agents should be specified by gender.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":" November","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135186646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Plasmodial Transcription Factors and Chromatin Modifiers as Drug Targets 作为药物靶点的转录因子和染色质修饰剂

Future Pharmacology Pub Date : 2023-11-09 DOI: 10.3390/futurepharmacol3040051

Luisa Fernanda Ortega Sepulveda, Gabriela Mendes de Oliveira, Elaine Hellen Nunes Chagas, Nele Wild, Franciarli Silva da Paz, Carsten Wrenger, Gerhard Wunderlich

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Considerations of Nystatin Roll in Oral Candidiasis Scenario and the COVID-19 Pandemic—A Review 制霉菌素卷筒在口腔念珠菌感染和COVID-19大流行中的应用综述

Future Pharmacology Pub Date : 2023-11-07 DOI: 10.3390/futurepharmacol3040050

Michelle Maria Gonçalves Barão de Aguiar, Renata Miliani Martinez, André Rolim Baby, Cristina Helena dos Reis Serra

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Erythrocyte Folyl Polyglutamate Synthetase Activity Profiling as a Potential Tool for the Prediction of Methotrexate Efficacy and Toxicity in Rheumatoid Arthritis 红细胞Folyl聚谷氨酸合成酶活性分析作为预测甲氨蝶呤对类风湿关节炎疗效和毒性的潜在工具

Future Pharmacology Pub Date : 2023-11-06 DOI: 10.3390/futurepharmacol3040049

Amar Kumar, Mudassar Iqbal Arain, Pooja Bhadbhade, Ryan Funk

{"title":"Erythrocyte Folyl Polyglutamate Synthetase Activity Profiling as a Potential Tool for the Prediction of Methotrexate Efficacy and Toxicity in Rheumatoid Arthritis","authors":"Amar Kumar, Mudassar Iqbal Arain, Pooja Bhadbhade, Ryan Funk","doi":"10.3390/futurepharmacol3040049","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040049","url":null,"abstract":"Methotrexate (MTX) is the cornerstone of therapy in the treatment of rheumatoid arthritis (RA). However, its efficacy and toxicity are variable and remain unpredictable. Interindividual variation in the metabolism of MTX by the enzyme folyl polyglutamate synthetase (FPGS) has been associated with response variability in RA. In this work, we propose the development of a FPGS phenotyping assay that can be evaluated as a tool for the prediction of efficacy and toxicity in patients with RA prior to initiating MTX therapy. FPGS activity was measured in erythrocyte lysate by monitoring methotrexate polyglutamate (MTX + Glun) formation using ultra-performance liquid chromatography tandem–mass spectrometry (UPLC/MS/MS). Erythrocyte FPGS activity was measured in newly diagnosed RA (n = 35) and osteoarthritis (n = 7) patients. The enzymatic assay was optimized for measuring FPGS activity in 25 µL of packed erythrocytes over two hours. The coefficient of variation for intra- and inter-day analysis was found to be 5% and 12%, respectively. The method was used to measure FPGS enzyme kinetics, resulting in a mean (SD) Km of 30.3 (4.8) µM and a Vmax of 612 (193) pmol MTX + Glu2/h/mL of packed erythrocytes. Mean (SD) erythrocyte FPGS activity in patients with RA was found to be 445.93 (344.50) pmol MTX + Glu2/h/mL and with a 26-fold difference in the range (range: 83–2179 pmol MTX + Glu2/h/mL) whereas for patients with OA, it was found to be 409.80 (157.66) pmol MTX + Glu2/h/mL with a 3.5-fold difference in the range (range: 200.95–683.93 pmol MTX + Glu2/h/mL). Monitoring erythrocyte FPGS activity may be a feasible strategy of phenotyping for methotrexate efficacy and toxicity in patients with RA.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"7 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135590159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Inflammasome Complex as a Therapeutic Approach in Inflammatory Diseases 炎性小体复合物在炎性疾病治疗中的应用

Future Pharmacology Pub Date : 2023-11-02 DOI: 10.3390/futurepharmacol3040048

Sharmim Sultana, Thanh Doan Viet, Tasmiha Amin, Esha Kazi, Luigina Micolucci, Abul Kalam Mohammad Moniruzzaman Mollah, Most Mauluda Akhtar, Md Soriful Islam

{"title":"Exploring Inflammasome Complex as a Therapeutic Approach in Inflammatory Diseases","authors":"Sharmim Sultana, Thanh Doan Viet, Tasmiha Amin, Esha Kazi, Luigina Micolucci, Abul Kalam Mohammad Moniruzzaman Mollah, Most Mauluda Akhtar, Md Soriful Islam","doi":"10.3390/futurepharmacol3040048","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040048","url":null,"abstract":"Inflammasomes, a group of multiprotein complexes, are essential in regulating inflammation and immune responses. Several inflammasomes, including nucleotide-binding domain leucine-rich repeat-containing protein 1 (NLRP1), NLRP3, NLRP6, NLRP7, NLRP12, interferon-inducible protein 16 (IFI16), NOD-like receptor family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and pyrin, have been studied in various inflammatory diseases. Activating inflammasomes leads to the processing and production of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18. The NLRP3 inflammasome is the most extensively studied and well characterized. Consequently, targeting inflammasomes (particularly NLRP3) with several compounds, including small molecule inhibitors and natural compounds, has been studied as a potential therapeutic strategy. This review provides a comprehensive overview of different inflammasomes and their roles in six inflammatory diseases, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, atherosclerosis, type 2 diabetes, and obesity. We also discussed different strategies that target inflammasomes to develop effective therapeutics.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"29 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135933546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antimicrobial Peptides and Their Assemblies 抗菌肽及其组装

Future Pharmacology Pub Date : 2023-10-19 DOI: 10.3390/futurepharmacol3040047

Ana Maria Carmona-Ribeiro

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Carrier-Mediated Delivery of Low-Molecular-Weight N-Containing Drugs across the Blood–Brain Barrier or the Blood–Retinal Barrier Using the Proton-Coupled Organic Cation Antiporter 利用质子偶联有机阳离子反转运蛋白，载体介导低分子量含n药物通过血脑屏障或血视网膜屏障的递送

Future Pharmacology Pub Date : 2023-10-12 DOI: 10.3390/futurepharmacol3040046

Toshihiko Tashima

{"title":"Carrier-Mediated Delivery of Low-Molecular-Weight N-Containing Drugs across the Blood–Brain Barrier or the Blood–Retinal Barrier Using the Proton-Coupled Organic Cation Antiporter","authors":"Toshihiko Tashima","doi":"10.3390/futurepharmacol3040046","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040046","url":null,"abstract":"While it is true that pharmacotherapy has achieved desired health outcomes, significant unmet medical needs persist in the field of central nervous system (CNS) drugs, particularly for neurodegenerative diseases such as Alzheimer’s disease, as well as ocular diseases such as diabetic retinopathy and age-related macular degeneration. Drugs cannot enter the brain from the bloodstream due to the presence of the blood–brain barrier (BBB). Similarly, they cannot enter the eyes from the bloodstream due to the blood–retina barrier (BRB), which is composed of the endothelium or the epithelium. Thus, innovative drug delivery systems that can overcome these barriers based on efflux transporters, hydrophobic lipid bilayer membranes, and tight junctions should be developed using patient-friendly techniques distinct from craniotomy procedures or intravitreal injections. Brain-penetrating CNS drugs and antihistamine drugs commonly share N-containing groups. These findings suggest that certain types of cation transporters are involved in their transportation across the cell membrane. Indeed, the proton-coupled organic cation (H+/OC) antiporter, whose specific characteristics remain unidentified, is responsible for transporting compounds with N-containing groups, such as clonidine and pyrilamine, at the BBB, and likely at the BRB as well. Therefore, well-designed low-molecular-weight drugs containing N-containing groups as transporter recognition units can enter the brain or the eyes through carrier-mediated transport. In this perspective review, I introduce the implementation and potential of H+/OC antiporter-mediated transport across the endothelium at the BBB or the BRB using drugs consciously designed with N-containing groups as their substrates.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"249 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136013826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Drug and Protein Interaction Network Construction for Drug Repurposing in Alzheimer’s Disease 阿尔茨海默病药物再利用的药物和蛋白质相互作用网络构建

Future Pharmacology Pub Date : 2023-10-12 DOI: 10.3390/futurepharmacol3040045

Georgios N. Dimitrakopoulos, Aristidis G. Vrahatis, Themis P. Exarchos, Marios G. Krokidis, Panagiotis Vlamos

{"title":"Drug and Protein Interaction Network Construction for Drug Repurposing in Alzheimer’s Disease","authors":"Georgios N. Dimitrakopoulos, Aristidis G. Vrahatis, Themis P. Exarchos, Marios G. Krokidis, Panagiotis Vlamos","doi":"10.3390/futurepharmacol3040045","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040045","url":null,"abstract":"Alzheimer’s disease is one of the leading causes of death globally, significantly impacting countless families and communities. In parallel, recent advancements in molecular biology and network approaches, guided by the Network Medicine perspective, offer promising outcomes for Alzheimer’s disease research and treatment. In this study, we aim to discover candidate therapies for AD through drug repurposing. We combined a protein-protein interaction (PPI) network with drug-target interactions. Experimentally validated PPI data were collected from the PICKLE meta-database, while drugs and their protein targets were sourced from the DrugBank database. Then, based on RNA-Seq data, we first assigned weights to edges to indicate co-expression, and secondly, estimated differential gene expression to select a subset of genes potentially related to the disease. Finally, small subgraphs (modules) were extracted from the graph, centered on the genes of interest. The analysis revealed that even if there is no drug targeting several genes of interest directly, an existing drug might target a neighboring node, thus indirectly affecting the aforementioned genes. Our approach offers a promising method for treating various diseases by repurposing existing drugs, thereby reducing the cost and time of experimental procedures and paving the way for more precise Network Medicine strategies.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135969257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Green Tea Extract Solid Dispersion Pellets with Enhanced Permeability for Hyperlipidemia 提高高脂血症渗透性的绿茶提取物固体分散颗粒

Future Pharmacology Pub Date : 2023-10-10 DOI: 10.3390/futurepharmacol3040044

Vinita Patole, Pranita Gaikwad, Shashikant Kharat, Pranali Jadhav, Sanjeevani Deshkar, Prabhanjan Giram

{"title":"Green Tea Extract Solid Dispersion Pellets with Enhanced Permeability for Hyperlipidemia","authors":"Vinita Patole, Pranita Gaikwad, Shashikant Kharat, Pranali Jadhav, Sanjeevani Deshkar, Prabhanjan Giram","doi":"10.3390/futurepharmacol3040044","DOIUrl":"https://doi.org/10.3390/futurepharmacol3040044","url":null,"abstract":"Green tea extract, rich in polyphenols like catechins, has been reported to have pharmacological benefits in patients with hyperlipidemia. The minimal membrane permeability of green tea limits its use in terms of bioavailability. To improve the permeability of green tea catechins in order to enhance theiranti-hyperlipidemia activity, a surfactant-based polymer was used to formulate a solid dispersion of green tea and convert it into commercially acceptable pellets. Green tea extract solid dispersions (GTE-SDs) were prepared withsolvent evaporation method using Soluplus® as a carrier. The GTE-SDs were evaluated for ex vivo permeation studies and characterized using FTIR, DSC, and XRD for confirming the formation of SD. The GTE-SDs exhibiting enhanced ex vivo permeation of EGCG were converted into a pellet formulation using the extrusion spheronization technique while being optimized using a 32 full factorial design. Soluplus® exhibited a four-fold improvement in the ex vivo permeation of EGCG from GTE-SD pellets (33.27%) as compared to GTE (10.43%) (p-value < 0.0001). In male Wistar rats, optimized GTE-SD pellets reduced the lipid blood profiles as compared to GTE (p-value < 0.0001). Thus, GTE-SD pellets can serve as an effective drug delivery platform for hyperlipidemia.","PeriodicalId":12592,"journal":{"name":"Future Pharmacology","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136358506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0