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The Extraction of Bioactive Agents from Calophyllum inophyllum L., and Their Pharmacological Properties 从茶树中提取生物活性物质及其药理特性
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-09 DOI: 10.3390/scipharm92010006
S. Ferdosh
Calophyllum inophyllum L. has been used for many generations by Pacific Islanders because of its numerous health and aesthetic advantages. The leaves, stems, roots, fruits, flowers, and seeds of this plant contain significant phytochemicals, including flavonoids, coumarins, fatty acids, and xanthones, which have been shown to have wound healing, analgesic, anti-inflammatory, antiaging, anti-arthritic, anti-cancer, anti-proliferative, anti-diabetic, anti-microbial, and anti-HIV effects. The chemical profiles and bioactive potential may vary due to different extraction techniques, plant parts, and geographical origins. Extraction is the essential first step in the analysis of bioactive compounds that leads to further separation, identification, and characterization. Conventional methods like maceration, Soxhlet, and percolation are often used to extract bioactive compounds from C. inophyllum. However, little study has been carried out on non-conventional methods such as pressured liquid extraction, supercritical fluid extraction (SFE), and ultrasound-assisted extraction. The SFE method can be used to extract bioactive compounds from C. inophyllum to retain their pharmacological properties for application in pharmaceutical and cosmetic products.
茶树(Calophyllum inophyllum L.)因其在健康和美学方面的众多优点,已被太平洋岛民世代相传。这种植物的叶、茎、根、果实、花和种子含有大量植物化学物质,包括类黄酮、香豆素、脂肪酸和氧杂蒽酮,已被证明具有伤口愈合、镇痛、消炎、抗衰老、抗关节炎、抗癌、抗增殖、抗糖尿病、抗微生物和抗艾滋病毒等功效。由于提取技术、植物部位和产地不同,化学成分和生物活性潜力也可能不同。萃取是分析生物活性化合物的第一步,也是进一步分离、鉴定和表征的关键步骤。浸渍法、索氏提取法和渗滤法等传统方法经常被用来提取叶绿素中的生物活性化合物。然而,对非常规方法,如加压液体萃取、超临界流体萃取(SFE)和超声波辅助萃取的研究还很少。超临界流体萃取法可用于提取茶叶中的生物活性化合物,以保留其药理特性,并应用于制药和化妆品中。
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引用次数: 0
The Risks of “Getting High” on Over-the-Counter Drugs during Pregnancy 孕期 "嗑药 "的风险
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-09 DOI: 10.3390/scipharm92010007
Bianca-Eugenia Ősz, Ruxandra Ștefănescu, Andreea Sălcudean, George Jîtcă, C. Vari
Easy access to over-the-counter (OTC) drugs makes it possible to procure active substances that normally used in therapeutic doses do not raise health problems. The use of high doses of OTC drugs containing codeine, loperamide, pseudoephedrine, diphenhydramine or dimenhydrinate, as well as the use of benzidamine systemically raises concerns regarding the increase in units sold. These drugs are used for recreational or euphorizing purposes, including by young women of childbearing age, psychoactive substance users representing a risk group in terms of the possibility of an unplanned pregnancy. Abusive consumption of OTC products during pregnancy is harmful, with consequences for both fetal and late development that can occur in the infant. This literature review presents the risks (teratogenicity, fetal toxicity, neonatal abstinence syndrome, etc.) associated with the use of potentially psychoactive OTC drugs to emphasize the importance of re-evaluating OTC classification and dispensing.
由于非处方药(OTC)很容易获得,因此可以购买到通常按治疗剂量使用不会引起健康问题的活性物质。大剂量使用含有可待因、洛哌丁胺、伪麻黄碱、苯海拉明或地美海明的非处方药以及全身使用苯海拉明引起了人们对销售量增加的担忧。这些药物被用于娱乐或兴奋目的,包括育龄年轻妇女,精神活性物质使用者是可能意外怀孕的风险群体。孕期滥用非处方药产品是有害的,会对胎儿和婴儿的后期发育造成影响。本文献综述介绍了与使用潜在精神活性非处方药相关的风险(致畸性、胎儿毒性、新生儿禁欲综合症等),以强调重新评估非处方药分类和配药的重要性。
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引用次数: 0
Diastereomers of Spheroidal Form and Commercially Available Taxifolin Samples 球形和市售紫杉叶素样品的非对映异构体
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-03 DOI: 10.3390/scipharm92010005
R. Terekhov, E. Melnikov, Ilya D. Nikitin, Margarita A. Tokareva, Tatyana A. Rodina, Anastasiya D. Savina, Denis I. Pankov, A. Zhevlakova, V. Beloborodov, I. Selivanova
Taxifolin is a natural polyphenol belonging to the class of flavonoids. The structure of this compound is characterized by the presence of two chiral centers. The spheroidal form of taxifolin (TAXs) has emerged as a promising modification due to enhanced solubility, higher safety profile, and long-term release from solid dosage forms. The study’s objective was to assess the diastereomeric content in TAXs and industrially produced samples of taxifolin. Considering the difference in the physico-chemical properties of diastereomers and based on the literature data, we developed a qualitative HPLC method. The chromatograms were recorded using a diode array detector at 290 nm and a mass spectrometer operated in negative ionization mode. Our data suggest that a biphenyl column and gradient elution using 0.1% formic acid in water and 0.2% formic acid in methanol, with the organic phase gradient from 7% to 21% and a flow rate of 0.65 mL/min for 15 min at 60 °C, provides the best conditions for the separation of taxifolin diastereomers. This method was validated for quantitative analysis. We discovered that the cis-isomer was present in all the analyzed samples, with its quantity ranging from 0.8% to 9.5%. TAXs can be considered a sample enriched with diastereomers.
紫杉叶素是一种天然多酚,属于类黄酮。这种化合物的结构特点是存在两个手性中心。球形紫杉醇(TAXs)具有更好的溶解性、更高的安全性以及可从固体制剂中长期释放等优点,因此已成为一种很有前途的改良剂。本研究的目的是评估 TAXs 和工业生产的紫杉叶素样品中的非对映异构体含量。考虑到非对映异构体在物理化学性质上的差异,并根据文献数据,我们开发了一种定性高效液相色谱法。使用二极管阵列检测器(290 nm)和质谱仪在负离子模式下记录色谱图。数据表明,采用联苯色谱柱,以 0.1% 甲酸水溶液和 0.2% 甲酸甲醇水溶液进行梯度洗脱,有机相梯度为 7% 至 21%,流速为 0.65 mL/min,在 60 °C 条件下持续 15 分钟,可为紫杉叶素非对映异构体的分离提供最佳条件。该方法已通过定量分析验证。我们发现,所有分析样品中都存在顺式异构体,其数量从 0.8% 到 9.5%不等。可以认为 TAXs 样品富含非对映异构体。
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引用次数: 0
Assessing the Influence of a Rotating Magnetic Field on Ibuprofen Permeability from Diverse Pharmaceutical Formulations 评估旋转磁场对不同药物制剂中布洛芬渗透性的影响
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-29 DOI: 10.3390/scipharm92010004
Anna Nowak, Paula Ossowicz-Rupniewska, M. Konopacki, Anna Muzykiewicz-Szymańska, Łukasz Kucharski, R. Rakoczy
This study introduces a novel approach for enhancing the transdermal permeability of ibuprofen through the skin by utilising a rotating magnetic field (RMF). The core objective is to systematically evaluate the influence of a 50 Hz RMF on ibuprofen’s skin permeability across various formulation types, each employing distinct physical forms and excipients. The experimental setup involved Franz cells with skin as the membrane, exposed to a 50 Hz RMF in conjunction with specific formulations. Subsequent comprehensive analysis revealed a notable increase in the transdermal transport of ibuprofen, irrespective of the formulation employed. Notably, the differences in the initial 30 min of permeation were particularly pronounced. Crucially, this investigation establishes that the application of a 50 Hz RMF resulted in a remarkable over-sevenfold increase in ibuprofen permeability compared to the control group without RMF exposure. It is noteworthy that in all semi-solid pharmaceutical formulations tested, RMF effectively reduced the delay time to zero, underscoring the efficiency of RMF in overcoming barriers to transdermal drug delivery. This research positions the application of RMF as a highly promising and innovative technology, significantly enhancing the transdermal penetration of anti-inflammatory and analgesic drugs through the skin. The demonstrated effectiveness of RMF across diverse formulations suggests its potential in transdermal drug delivery, offering a novel and efficient strategy for improving therapeutic outcomes in the administration of ibuprofen and potentially other pharmaceutical agents.
本研究介绍了一种利用旋转磁场(RMF)提高布洛芬透皮渗透性的新方法。其核心目标是系统地评估 50 赫兹 RMF 对布洛芬在各种制剂类型中的皮肤渗透性的影响,每种制剂都采用了不同的物理形式和辅料。实验装置包括以皮肤为膜的弗兰茨细胞,暴露在 50 赫兹 RMF 和特定配方中。随后的综合分析表明,无论采用哪种制剂,布洛芬的透皮转运能力都有显著提高。值得注意的是,最初 30 分钟的渗透差异尤为明显。最重要的是,这项研究证实,与未接触 50 赫兹 RMF 的对照组相比,使用 50 赫兹 RMF 后布洛芬的渗透性显著增加了七倍多。值得注意的是,在所有测试的半固体药物制剂中,RMF 都能有效地将延迟时间缩短为零,这表明 RMF 能有效克服透皮给药的障碍。这项研究将 RMF 的应用定位为一项极具前景的创新技术,它能显著增强消炎药和镇痛药在皮肤中的透皮渗透。RMF在不同配方中的有效性表明了它在透皮给药方面的潜力,为改善布洛芬和其他潜在药物的治疗效果提供了一种新颖而有效的策略。
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引用次数: 0
Inhibitory Effect of Mistletoe Ointment on DNCB-Induced Atopic Dermatitis in BALB/c Mice 槲寄生软膏对 BALB/c 小鼠 DNCB 诱导的特应性皮炎的抑制作用
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-29 DOI: 10.3390/scipharm92010003
Chang-Eui Hong, S. Lyu
Atopic dermatitis (AD) is increasingly prevalent globally. However, the frequent and prolonged use of corticosteroids, which are commonly employed for AD treatment, carries potential side effects. Korean mistletoe (Viscum album L. var. coloratum), a perennial parasitic plant, has demonstrated various biological effects. In this study, we conducted in vivo investigations to determine whether Korean mistletoe possesses anti-inflammatory effects that play pivotal roles in regulating the pathological mechanisms of AD. BALB/c mice with AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) were utilized to explore the therapeutic effects of 1% and 2% Korean mistletoe extract (KME) ointments. The KME ointment was topically applied to the dorsal surface of the BALB/c mice, and they were categorized into four distinct groups: normal, DNCB-induced, DNCB-induced with 1% KME ointment, and DNCB-induced with 2% KME ointment. Each assessment parameter employed to evaluate the curative impact of the KME ointment displayed improvement with the application of the 1% KME ointment. While the effects observed were less pronounced than those of the 1% KME ointment, the overall therapeutic outcomes were also evident with the utilization of the 2% KME ointment. The results suggest the potential of Korean mistletoe as a viable therapeutic agent for AD. Further investigations are warranted to elucidate the underlying mechanisms of action.
特应性皮炎(AD)在全球的发病率越来越高。然而,频繁和长期使用皮质类固醇治疗特应性皮炎有潜在的副作用。韩国槲寄生(Viscum album L. var. coloratum)是一种多年生寄生植物,具有多种生物效应。在本研究中,我们进行了体内研究,以确定韩国槲寄生是否具有抗炎作用,从而在调节 AD 的病理机制中发挥关键作用。我们利用 2,4-二硝基氯苯(DNCB)诱导的 BALB/c 小鼠 AD 样皮损,探讨了 1% 和 2% 韩国槲寄生提取物(KME)软膏的治疗效果。将KME软膏局部涂抹于BALB/c小鼠的背表面,并将其分为四组:正常组、DNCB诱导组、DNCB诱导组(含1% KME软膏)和DNCB诱导组(含2% KME软膏)。用于评估 KME 软膏疗效的每项评估参数都显示,使用 1% KME 软膏后情况有所改善。虽然观察到的效果不如1% KME软膏明显,但使用2% KME软膏后,总体治疗效果也很明显。这些结果表明,韩国槲寄生有可能成为一种治疗注意力缺失症的可行药物。还需要进一步研究以阐明其潜在的作用机制。
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引用次数: 0
Polymorphisms in Drug Transporter and Metabolism Genes Associated with Resistance to Imatinib in Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis 药物转运体和代谢基因的多态性与慢性粒细胞白血病患者对伊马替尼的耐药性有关:系统回顾与元分析
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-25 DOI: 10.3390/scipharm92010002
Ana Marcela Arrieta Gómez, María Antonia Díaz-Mendoza, Yesit Bello Lemus, Grethel León-Mejía, Martha Lucia Ruiz Benitez
The aim of this study was to establish the relationship between different polymorphisms in drug transporter and metabolizer genes and resistance to imatinib in chronic myeloid leukemia (CML). For this purpose, an exhaustive search was carried out in the Scopus, Web of Science, and PubMed databases using different combinations of keywords with different inclusion and exclusion criteria. The meta-analysis included nine studies that met the established criteria. The results of the study showed that the polymorphic variants AG and GG of CYP3A5*3 are associated with response to treatment, presenting a significantly lower risk with resistance to imatinib. Likewise, the variants T1236C and G2677T/A of the ABCB1 gene show a significant association with treatment efficacy. In addition, the genetic polymorphism 1236T, homozygous CC of the MDR1 gene, significantly influences the increased risk of cytogenetic relapse and the polymorphic variant 361G>A GA of the SLCO1A2 gene significantly affects the complete molecular response.
本研究旨在确定药物转运体和代谢基因的不同多态性与慢性髓性白血病(CML)患者对伊马替尼耐药性之间的关系。为此,我们在 Scopus、Web of Science 和 PubMed 数据库中使用不同的关键词组合和不同的纳入和排除标准进行了详尽的检索。荟萃分析包括九项符合既定标准的研究。研究结果表明,CYP3A5*3的多态变异AG和GG与治疗反应有关,对伊马替尼耐药的风险明显较低。同样,ABCB1 基因的变异体 T1236C 和 G2677T/A 与疗效也有显著关联。此外,MDR1 基因的同源 CC 基因多态性 1236T 显著影响细胞遗传学复发风险的增加,SLCO1A2 基因的多态性变异 361G>A GA 显著影响完全分子反应。
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引用次数: 0
In Silico Activity Prediction and Docking Studies of the Binding Mechanisms of Levofloxacin Structure Derivatives to Active Receptor Sites of Bacterial Type IIA Topoisomerases 左氧氟沙星结构衍生物与细菌 IIA 型拓扑异构酶活性受体位点结合机制的硅学活性预测和对接研究
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-20 DOI: 10.3390/scipharm92010001
E. Uspenskaya, Vasilisa A. Sukhanova, Ekaterina S. Kuzmina, T. Pleteneva, Olga V. Levitskaya, Timur M. Garaev, Anton V. Syroeshkin
The need for new antimicrobial agents (AntAg) is driven by the persistent antibiotic resistance in microorganisms, as well as the increasing frequency of pandemics. Due to the deficiency of AntAg, research aimed at developing speedy approaches to find new drug candidates is relevant. This study aims to conduct an in silico study of the biological activity spectrum as well as the molecular binding mechanisms of four structurally different forms of levofloxacin (Lvf) with bacterial topoisomerases targets of type IIA (DNA gyrase and topoisomerase IV) to enable the development of drugs with an improved characterization of the safety profile. To achieve this goal, a number of software products were used, such as ChemicPen v. 2.6, PyMol 2.5, Avogadro 1.2.0, PASS, AutoDockTools 1.5.7 with the new generation software Autodock Vina. These software products are the first to be made available for visualization of clusters with determination of ligand-receptor pair binding affinity, as well as clustering coordinates and proposed mechanisms of action. One of the real structures of Lvf, a decarboxylated derivative, was obtained with tribochemical (TrbCh) exposure. The action spectrum of molecular ligands is described based on a Bayesian probability activity prediction model (PASS software Version 2.0). Predicted and real (PMS and RMS) molecular structures of Lvf, with decreasing levels of structural complexity, were translated into descriptors via Wiener (W), Balaban (Vs), Detour (Ip), and Electropy € indices. The 2D «structure-activity» diagrams were used to differentiate closely related structures of levofloxacin. PMS and RMS were visualized as 3D models of the ligand-receptor complexes. The contact regions of RMS and PMS with key amino acid residues—SER-79, DT-15, DG-1, DA-1—were demonstrated. The intra- and inter-molecular binding sites, data on free energy (affinity values, kcal/mol), the binding constant Kb (M−1), and the number of clusters are presented. The research results obtained from the presented in silico approach to explore the spectrum of action find quantitative “structure-activity” correlations, and predict molecular mechanisms may be of applied interest for directed drug discovery.
微生物对抗生素的持久耐药性以及大流行病的日益频繁,都促使人们需要新的抗菌剂(AntAg)。由于 AntAg 的缺乏,旨在开发快速方法寻找新候选药物的研究具有现实意义。本研究旨在对四种结构不同的左氧氟沙星(Lvf)与细菌拓扑异构酶 IIA 型靶标(DNA 回旋酶和拓扑异构酶 IV)的生物活性谱和分子结合机制进行硅学研究,以便开发出具有更好安全性特征的药物。为实现这一目标,使用了许多软件产品,如 ChemicPen v. 2.6、PyMol 2.5、Avogadro 1.2.0、PASS、AutoDockTools 1.5.7 和新一代软件 Autodock Vina。这些软件产品是首批可用于确定配体-受体配对结合亲和力、聚类坐标和拟议作用机制的可视化聚类软件。Lvf 是一种脱羧衍生物,其真实结构之一是通过摩擦生化(TrbCh)暴露获得的。分子配体的作用谱是根据贝叶斯概率活性预测模型(PASS 软件 2.0 版)描述的。通过 Wiener (W)、Balaban (Vs)、Detour (Ip) 和 Electropy € 指数将 Lvf 的预测分子结构和真实分子结构(PMS 和 RMS)转化为描述符,结构复杂程度依次降低。二维 "结构-活性 "图用于区分左氧氟沙星的密切相关结构。PMS 和 RMS 被视为配体-受体复合物的三维模型。展示了 RMS 和 PMS 与关键氨基酸残基--SER-79、DT-15、DG-1、DA-1 的接触区域。此外,还给出了分子内和分子间的结合位点、自由能数据(亲和力值,kcal/mol)、结合常数 Kb(M-1)和簇数。所介绍的硅学方法可用于探索药物的作用谱,找到定量的 "结构-活性 "相关性,并预测分子机理。
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引用次数: 0
Analysis of Beneficial Effects of Flavonoids in Patients with Atherosclerosis Risk on Blood Pressure or Cholesterol during Random Controlled Trials: A Systematic Review and Meta-Analysis 在随机对照试验中分析黄酮类化合物对有动脉粥样硬化风险的患者的血压或胆固醇的有益影响:系统回顾与元分析
IF 2.5 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-22 DOI: 10.3390/scipharm91040055
Rosa Edith Grijalva-Guiza, Thais Lucía Grijalva-Montano, Mariana Cuautle, E. Quiroga‐González, L. R. Hernández, Alicia Ortega Aguilar, A. M. Jiménez-Garduño
Flavonoids are plant-secondary metabolites with cardiovascular protective properties. Few studies have examined specific flavonoid classes or pure flavonoids concerning some common cardiovascular risks. To obtain information in a systematic review to analyze in a meta-analysis, data were recovered regarding flavonoid intake in random controlled trials and atherosclerosis disease, related to risk factors such as blood pressure, total cholesterol (TC), and low-density lipoprotein cholesterol (LDLc). Our aim was to conduct a meta-analysis using the Scopus and PubMed databases without restrictions on the year of publication, extracting articles over the period 1–15 April 2023, searching for randomized controlled trials (RCTs) that investigated different types of flavonoids, measuring blood pressure and low-density cholesterol plasmatic concentration. This paper’s Prospero registration is CRD 42023414153. There were 19 RCTs: twelve RCTs were considered for blood pressure data analysis and fifteen RCTs for total cholesterol and LDL cholesterol data analysis. The meta-analysis showed no significant differences between placebo treatments and treatments with different flavonoids on blood pressure. However, there was a significant difference found in quantitative analysis for TC and LDLc. In conclusion, flavonoid consumption can be associated with a lower risk of LDLc and TC, and more RCTs are needed to specify the effect of more types of pure flavonoids in atherosclerotic patients.
类黄酮是植物的次级代谢产物,具有保护心血管的特性。很少有研究针对一些常见的心血管风险对特定类黄酮或纯类黄酮进行研究。为了在系统综述中获取信息并进行荟萃分析,我们在随机对照试验中收集了有关类黄酮摄入量和动脉粥样硬化疾病的数据,这些数据与血压、总胆固醇(TC)和低密度脂蛋白胆固醇(LDLc)等风险因素有关。我们的目的是利用Scopus和PubMed数据库进行荟萃分析,不限制发表年份,提取2023年4月1日至15日期间的文章,搜索研究不同类型类黄酮、测量血压和低密度胆固醇质浓度的随机对照试验(RCT)。本文的 Prospero 注册号为 CRD 42023414153。共有 19 项 RCT:其中 12 项 RCT 用于血压数据分析,15 项 RCT 用于总胆固醇和低密度胆固醇数据分析。荟萃分析表明,安慰剂疗法和不同类黄酮疗法对血压的影响没有显著差异。不过,在对总胆固醇和低密度脂蛋白胆固醇进行定量分析时,发现两者之间存在明显差异。总之,食用类黄酮与降低低密度脂蛋白胆固醇和高密度脂蛋白胆固醇的风险有关,需要进行更多的研究与试验,以明确更多种类的纯类黄酮对动脉粥样硬化患者的影响。
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引用次数: 0
Monitoring Cutaneous Leishmaniasis Lesions in Mice Undergoing Topical Miltefosine Treatment 局部米替福辛治疗小鼠皮肤利什曼病病变监测
Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-09 DOI: 10.3390/scipharm91040054
Laura Fernanda Neira, Julio Cesar Mantilla, Patricia Escobar
A study was conducted on BALB/c mice infected with Leishmania (Leishmania) amazonensis to analyse the effects of 0.5% miltefosine (MTF) hydrogel treatment on cutaneous leishmaniasis (CL) lesions. The mice were treated for 25 days topically, and lesion sizes, parasite loads, histopathology, ultrastructure, cytokines including interleukin 4 (IL-4), tumour necrosis factor alfa (TNFα), interferon gamma (IFNγ), IL-10, and vascular endothelial growth factor (VEGF) profiles were evaluated on days 0, 12, 25, and 85. After 12 days of treatment, the lesion sizes and parasite numbers decreased. By day 60 post treatment, there were no lesions and only a few parasites. At day 25, there was a temporary papillomatosis reaction, an increase in mast cells, a few giant cells, and granulomas, and a decrease in diffuse inflammatory infiltrate and parasites. Transmission electron microscopy (TEM) examination showed early ultrastructural changes, including macrophages without parasites and vacuoles containing electrodense material. At the different evaluated times, the cytokine regulation indexes (ICRs) decreased for IL-4, TNFα, and VEGF. According to the study, the 0.5% MTF hydrogel was effective and showed positive results from the early stages of usage. The MTF directly targeted parasites, downregulated the release of IL-4, TNFα, and VEGF, increased mast cell production, and induced granuloma reaction during evaluation periods.
本研究对感染亚马逊利什曼原虫(Leishmania)的BALB/c小鼠进行了研究,分析0.5%米替福辛(MTF)水凝胶治疗对皮肤利什曼病(CL)病变的影响。小鼠局部治疗25天,在第0、12、25和85天评估病变大小、寄生虫载量、组织病理学、超微结构、细胞因子包括白细胞介素4 (IL-4)、肿瘤坏死因子α (TNFα)、干扰素γ (IFNγ)、IL-10和血管内皮生长因子(VEGF)谱。治疗12天后,病变大小和寄生虫数量下降。到治疗后第60天,没有病变,只有少量寄生虫。第25天,出现暂时性乳头状瘤反应,肥大细胞、少量巨细胞和肉芽肿增加,弥漫性炎症浸润和寄生虫减少。透射电镜(TEM)检查显示早期超微结构改变,包括无寄生虫的巨噬细胞和含有电致密物质的液泡。在不同的评估时间,细胞因子调节指数(ICRs) IL-4、tnf - α、VEGF均下降。根据这项研究,0.5% MTF水凝胶是有效的,从使用的早期阶段就显示出积极的结果。在评估期间,MTF直接靶向寄生虫,下调IL-4、TNFα和VEGF的释放,增加肥大细胞的产生,并诱导肉芽肿反应。
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引用次数: 0
siRNA Targeting PDE5A Partially Restores Vascular Damage Due to Type 1 Diabetes in a Streptozotocin-Induced Rat Model siRNA靶向PDE5A在链脲佐菌素诱导的1型糖尿病大鼠模型中部分恢复血管损伤
Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-08 DOI: 10.3390/scipharm91040052
Vanessa Giselle Garcia-Rubio, Sandra Edith Cabrera-Becerra, Sergio Adrian Ocampo-Ortega, Citlali Margarita Blancas-Napoles, Vivany Maydel Sierra-Sánchez, Rodrigo Romero-Nava, Rocío Alejandra Gutiérrez-Rojas, Fengyang Huang, Enrique Hong, Santiago Villafaña
Diabetes mellitus is a metabolic disease that can produce different alterations such as endothelial dysfunction, which is defined as a decrease in the vasodilator responses of the mechanisms involved such as the nitric oxide (NO) pathway. The overexpression of PDE5A has been reported in diabetes, which causes an increase in the hydrolysis of cGMP and a decrease in the NO pathway. For this reason, the aim of this study was to evaluate whether siRNAs targeting PDE5A can reduce the endothelial dysfunction associated with diabetes. We used male Wistar rats (200–250 g) that were administered streptozotocin (STZ) (60 mg/kg i.p) to induce diabetes. Two weeks after STZ administration, the siRNAs or vehicle were administered and then, at 4 weeks, dose–response curves to acetylcholine were performed and PDE5A mRNA levels were measured by RT-PCR. siRNAs were designed by the bioinformatic analysis of human–rat FASTA sequences and synthesised in the Mermade-8 equipment. Our results showed that 4 weeks of diabetes produces a decrease in the vasodilator responses to acetylcholine and an increase in the expression of PDE5A mRNA, while the administration of siRNAs partially restores the vasodilator response and decreases PDE5A expression. We conclude that the administration of siRNAs targeting PDE5A partially reverts the endothelial impairment associated with diabetes.
糖尿病是一种代谢性疾病,可产生不同的改变,如内皮功能障碍,其定义为一氧化氮(NO)途径等相关机制的血管舒张反应减少。PDE5A在糖尿病中过表达,导致cGMP水解增加,NO通路减少。因此,本研究的目的是评估靶向PDE5A的sirna是否可以减少与糖尿病相关的内皮功能障碍。我们用雄性Wistar大鼠(200-250 g)注射链脲佐菌素(STZ) (60 mg/kg i.p)诱导糖尿病。STZ给药2周后,给予sirna或载体,然后在4周时,绘制乙酰胆碱的剂量-反应曲线,并通过RT-PCR检测PDE5A mRNA水平。sirna通过人大鼠FASTA序列的生物信息学分析设计,并在Mermade-8设备上合成。我们的研究结果显示,糖尿病4周后,乙酰胆碱对血管舒张剂的反应降低,PDE5A mRNA的表达增加,而sirna的使用部分恢复了血管舒张剂的反应,降低了PDE5A的表达。我们得出结论,靶向PDE5A的sirna的管理部分地恢复了与糖尿病相关的内皮损伤。
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Scientia Pharmaceutica
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