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Content of selected polyphenolic compounds in four Sambucus nigra l. cultivars in relation to their antimicrobial activity 四种黑三叶草栽培品种中某些多酚化合物的含量与其抗菌活性的关系
Pub Date : 2024-02-01 DOI: 10.32383/appdr/175051
I. Korona-Głowniak, Martyna Kasela, Barbara Pliszka, D. Zalewski, Anna Malm
European elderberry (Sambucus nigra L.) fruits constitute a valuable source of biologically active compounds useful in the pharmaceutical industry. We aimed to determine the content of chosen polyphenolic compounds in fruit extracts from four cultivars of elderberry (Alleso, Korsor, Sampo, Samyl) and their relation to antibacterial and antifungal activity. The content of polyphenols was determined with the use of high-performance liquid chromatography (HPLC), while antimicrobial activity, including minimum inhibitory concentration (MIC), minimum bactericidal (MBC) or fungicidal (MFC) concentration, was studied with the use of microbroth dilution method. HPLC analysis revealed the presence of concentrations of cyanidin glycosides, caffeic and quercetin derivatives depending on the plant cultivar. The extracts exhibited the highest antibacterial activity against Staphylococcus spp. (MIC = 0.313 – 0.625 mg/mL) and Helicobacter pylori (MIC = 0.313 – 1.25 mg/mL) and antifungal against Candida albicans and C. parapsilosis (MIC = 0.313 – 2.5 mg/mL). Results showed that the concentration of cyanidin glycosides, caffeic and quercetin derivatives depended on the analyzed S. nigra L. cultivar and pointed towards a correlation between their high content and antimicrobial activity. These results support the idea that elderberry fruits contain bioactive compounds providing them significant antimicrobial potential.
欧洲接骨木(Sambucus nigra L.)果实是制药业有用的生物活性化合物的宝贵来源。我们的目的是测定四种接骨木(Alleso、Korsor、Sampo、Samyl)果实提取物中精选多酚化合物的含量及其与抗菌和抗真菌活性的关系。使用高效液相色谱法(HPLC)测定了多酚类化合物的含量,并使用微流稀释法研究了抗菌活性,包括最低抑菌浓度(MIC)、最低杀菌浓度(MBC)或杀真菌浓度(MFC)。高效液相色谱分析显示,根据植物品种的不同,青花素苷、咖啡酸和槲皮素衍生物的浓度也不同。提取物对葡萄球菌属(MIC = 0.313 - 0.625 mg/mL)和幽门螺旋杆菌(MIC = 0.313 - 1.25 mg/mL)的抗菌活性最高,对白色念珠菌和副丝状芽孢杆菌(MIC = 0.313 - 2.5 mg/mL)的抗真菌活性最高。结果表明,花青素苷、咖啡酸和槲皮素衍生物的浓度取决于所分析的黑接骨木栽培品种,并指出它们的高含量与抗菌活性之间存在相关性。这些结果支持了接骨木果实含有生物活性化合物的观点,使其具有显著的抗菌潜力。
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引用次数: 0
Emulsions, their quality and importance in food, cosmetic, and pharmaceutical industries 乳液及其质量和在食品、化妆品和制药业中的重要性
Pub Date : 2024-01-30 DOI: 10.32383/appdr/174249
Magdalena Wozniak, M. Kowalska, Piotr Ludwiński
The paper presents the most important issues in the stability of emulsion systems. It describes the composition of emulsions and indicates the factors determining the quality of these systems. The most popular industrial areas in which these systems are convenient and useful form are indicated. The applications of emulsion systems in the pharmaceutical, cosmetic and food industries are described in detail, including the advantages and disadvantages of such systems. It was concluded that it is still one of the most popular forms of products.
本文介绍了乳液体系稳定性方面最重要的问题。它描述了乳液的组成,并指出了决定这些体系质量的因素。此外,还介绍了这些体系最常用的工业领域。详细介绍了乳液体系在制药、化妆品和食品工业中的应用,包括这类体系的优缺点。结论是,它仍然是最受欢迎的产品形式之一。
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引用次数: 0
Monoterpenes as Medicinal Agents: Exploring the Pharmaceutical Potential of p-Cymene, p-Cymenene, and γ-Terpinene 作为药剂的单萜类化合物:探索对伞花烯、对伞花烯和γ-萜品烯的药用潜力
Pub Date : 2024-01-30 DOI: 10.32383/appdr/178242
Sylwia Bagińska, Aleksandra Golonko, R. Świsłocka, W. Lewandowski
This review highlights the therapeutic propeties of monoterpenes, particularly γ-terpinene, p-cymene, and p-cymenene, found in essential oils derived from various plants. These compounds are known for their analgesic, anticancer, anti-inflammatory, and antimicrobial properties. γ-Terpinene is recognized for its potent antioxidant propeties and is a constituent of oils from plants such as cumin and thyme. p-cymene, found in over 100 plant species, is noted for its antiviral and antibacterial properties and is considered safe by IFRA standards. p-Cymenene, with its distinct aroma, is detected in parsley and turmeric oils and is known for its antibacterial and antioxidant activities. The antimicrobial properties of γ-terpinene and p-cymene are highlighted, demonstrating their effectiveness in treating various skin conditions and reducing airborne microbes. Their selective antimicrobial activity preserves the integrity of the microbiome, offering a balanced approach to infection control. The anti-inflammatory properties of γ-terpinene are emphasized, with studies indicating its role in modulating cytokine production, underscoring its potential in the treatment of inflammation. Additionally, its antinociceptive effects suggest that it is a safe analgesic. In cancer treatment, the antiproliferative effects of γ-terpinene and p-cymene are being explored, highlighting their potential for targeted cancer therapy. This review aims to consolidate knowledge about these monoterpenes and promote a deeper understanding of their medical applications and safety. The knowledge gained is expected to stimulate further research, potentially leading to innovative applications in pharmaceutical and medical fields and harnessing the potential of -terpinene, p-cymene, and p-cymenene.
这篇综述重点介绍了单萜烯类化合物的治疗特性,尤其是γ-萜品烯、对-千层烯和对-千层烯,它们存在于从各种植物中提取的精油中。这些化合物具有镇痛、抗癌、消炎和抗菌的功效。γ-萜品烯被认为具有强大的抗氧化能力,是小茴香和百里香等植物精油的成分之一;对伞花烯存在于 100 多种植物中,具有抗病毒和抗菌特性,被 IFRA 标准认为是安全的。γ-萜品烯和对-月桂烯的抗菌特性得到了强调,证明了它们在治疗各种皮肤病和减少空气中微生物方面的功效。它们的选择性抗菌活性可以保护微生物群的完整性,提供一种平衡的感染控制方法。研究表明,γ-萜品烯具有调节细胞因子分泌的作用,强调了它在治疗炎症方面的潜力。此外,其抗痛作用表明它是一种安全的镇痛剂。在癌症治疗方面,人们正在探索γ-松油烯和对伞花烃的抗增殖作用,这凸显了它们在癌症靶向治疗方面的潜力。本综述旨在巩固有关这些单萜的知识,并促进对其医疗应用和安全性的深入了解。所获得的知识有望促进进一步的研究,从而有可能在制药和医疗领域实现创新应用,并利用-萜品烯、对-月桂烯和对-月桂烯的潜力。
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引用次数: 0
Structural polymorphism research of alverine citrate 柠檬酸阿尔维林的结构多态性研究
Pub Date : 2024-01-30 DOI: 10.32383/appdr/175084
Magdalena Janczura, N. Rosiak, Marta Gromek, J. Cielecka‐Piontek
The study compares the active substance alverine citrate from three commercial sources in order to demonstrate polymorphic forms using the XRPD, SEM, and ATR-FTIR techniques. Based on the solubility tests of alverine citrate, a hard capsule was prepared with the highest possible dose of the active substance. The release profiles of alverine citrate and its stability were also investigated. XRPD and ATR-FTIR analysis shows that all alverine citrate samples (despite differences in the synthesis process) are in the same polymorphic Form I. Scanning electron micrographs of alverine citrate from each manufacturer show differences in morphology (texture). The solubility studies confirmed the complete solubility of the highest dose of alverine citrate in media with a pH of 1.2-6.8. The release studies show that the release of the active substance, regardless of the manufacturer type, meets the immediate release requirement. Accelerated stability studies confirm the stability of the alverine citrate from selected manufacturers. As a result, the manufacturer of the final medicinal product may allow their inter-changeability during production without compromising the safety or efficacy of the medicinal product.
本研究比较了三种商业来源的枸橼酸阿尔维林活性物质,以便利用 XRPD、SEM 和 ATR-FTIR 技术展示其多晶型。根据枸橼酸阿尔维林的溶解度测试结果,制备了含有最高剂量活性物质的硬胶囊。此外,还研究了枸橼酸阿尔维林的释放曲线及其稳定性。XRPD 和 ATR-FTIR 分析表明,所有枸橼酸阿尔维林样品(尽管合成工艺不同)都具有相同的多晶型 I。溶解度研究证实,最高剂量的枸橼酸阿尔维林在 pH 值为 1.2-6.8 的介质中完全溶解。释放研究表明,无论生产商是哪种类型,活性物质的释放都符合立即释放的要求。加速稳定性研究证实了选定制造商生产的枸橼酸阿尔维林的稳定性。因此,最终药品的生产商可以允许在生产过程中相互更换,而不会影响药品的安全性或有效性。
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引用次数: 0
BIOINFORMATICS-ASSISTED SELECTION AND ASSOCIATION OF MATRIX MEATLLOPROTEINASE-9 (MMP-9) POLMORPHISM rs17576 WITH DIABETIC RETINOPATHY 经生物分析鉴定的肉毒蛋白酶-9 (MMP-9)多态性 rs17576 与糖尿病性视网膜病变的分离与相关性研究
Pub Date : 2024-01-30 DOI: 10.32383/appdr/174802
F. K. Alswailmi
AbstractPurpose: Components of inflammatory pathways had a major role in the development of diabetic induced complications including the retinopathy. Therefore, in the present study bioinformatics assisted predicted the role of polymorphism of genes in the coding sequence of inflammatory pathway mediator matrix metallopeptidase 9 (MMP9) was determined in the development of diabetic retinopathy among the population of south Asian countries. Methods: Non-synonymous single nucleotide polymorphisms (SNP) rs17576 in MMP9 (c.836A>G; p.Q279R) was bioinformatically analyzed as well as genotyping was done in 419 individuals with type 2 diabetes (219 individuals with diabetic retinopathy (DR) and 200 individuals with diabetic non-retinopathic (DNR) while 200 healthy individuals were recruited as control for both DR and DNR patients.Results: In silico assisted functional effect due to kinetic changes in protein structure was observed for MMP9 rs17576 (p.Q279R). In addition, genetic analysis revealed significant association of the “G” allele with diabetic individuals most prominently females (χ²=12.65, p<0.05, OR=0.47 [95% CI=0.30-0.73, p<0.05])Conclusion: The rs17576 (c.836A>G; p.Q279R) polymorphism of MMP9 was found to influence protein structure and functional and was observed to provide protection, dominantly in females, against the diabetic retinopathy.
摘要目的:炎症通路的成分在糖尿病诱发的并发症(包括视网膜病变)的发展过程中起着重要作用。因此,本研究在生物信息学的辅助下,预测了炎症通路介质基质金属肽酶 9(MMP9)编码序列中基因的多态性在南亚国家人群糖尿病视网膜病变发展中的作用。研究方法对MMP9(c.836A>G; p.Q279R)中的非同义单核苷酸多态性(SNP)rs17576进行生物信息学分析,并对419名2型糖尿病患者(219名糖尿病视网膜病变(DR)患者和200名糖尿病非视网膜病变(DNR)患者)进行基因分型,同时招募200名健康人作为DR和DNR患者的对照:MMP9 rs17576 (p.Q279R)因蛋白质结构的动力学变化而产生的辅助功能效应在硅学中被观察到。此外,遗传分析表明,"G "等位基因与糖尿病患者(主要是女性)有显著关联(χ²=12.65,pG;p.Q279R)。
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引用次数: 0
Soft Gelatine Capsules- Critical Quality Attributes of Chosen Excipients and Capsules Parameters Following the Quality by Design Concept 明胶软胶囊--按照设计质量理念选择辅料和胶囊参数的关键质量属性
Pub Date : 2023-11-27 DOI: 10.32383/appdr/172348
Barbara Owczarek, E. Łukowska-Chojnacka
Soft gel capsules are a common form of medicine and food supplements. Quality, productivity and manufacturing time is crucial for producers during their development and industrial operations. To ensure the best quality of the product, it is necessary to know all critical process steps and parameters. The use of QbD elements is to ensure the quality of the drug product throughout its "life cycle". Quality by design (QbD) and its elements are described by the International Council of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and in their guideline - chapter ICH Q8 (Pharmaceutical Development). One of the first steps in pharmaceutical product development is to prepare Quality Target Product Profile (QTPP) and analyse Critical Material Attributes (CMAs) and Critical Quality Attributes (CQAs) of excipients, active pharmaceutical ingredient (API) and final product. During this research, we investigated the CQAs of the excipients used in vitamin D3 soft gelatin capsules containing high doses of cholecalciferol, from 10 000 to 200 000 IU per capsule. We considered the viscosity of the gelatin mass, the effect of the addition of dye on the viscosity, and the impact of the colour of the gelatin mass on the active substance content in the final capsules. It was also investigated oily carriers (medium chain triglycerides and safflower oil) and antioxidants (alpha-tocopherol acetate vs butylhydroxytoluene), and their effect on API concentration in the capsule.
软胶囊是一种常见的药品和食品补充剂。质量、生产率和生产时间对生产商的研发和工业运营至关重要。为了确保产品的最佳质量,有必要了解所有关键的工艺步骤和参数。使用 QbD 要素是为了确保药品在整个 "生命周期 "内的质量。国际人用药品技术要求协调理事会(ICH)在其指南 ICH Q8 章(药品开发)中对设计质量(QbD)及其要素进行了描述。医药产品开发的第一步是编制质量目标产品简介 (QTPP),分析辅料、活性药物成分 (API) 和最终产品的关键材料属性 (CMA) 和关键质量属性 (CQA)。在这项研究中,我们调查了维生素 D3 软胶囊所用辅料的 CQA,该胶囊含有高剂量的胆钙化醇(每粒 10 000 至 200 000 IU)。我们考虑了明胶块的粘度、添加染料对粘度的影响以及明胶块的颜色对最终胶囊中活性物质含量的影响。我们还研究了油性载体(中链甘油三酯和红花油)和抗氧化剂(α-生育酚醋酸酯和丁基羟基甲苯),以及它们对胶囊中原料药浓度的影响。
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引用次数: 0
Salidroside Enhances Aerobic Swimming to Improve Oxidative Aging Induced by D-Galactose in Mice 水杨梅甙增强有氧游泳能力,改善小鼠由 D-半乳糖诱发的氧化衰老
Pub Date : 2023-11-27 DOI: 10.32383/appdr/172999
Jing Zhang, Xiankun Dai, Mengwei Wang, Jing Song, X. Long, Y. Qian, Xin Zhao
This study observed the effect of salidroside on improving oxidative aging induced by D-galactose in mice by enhancing aerobic swimming. In this study, the oxidative aging model of mice was established by D-galactose, and the changes of organ index, histopathological changes, and mRNA expression in serum and tissue of oxidative aging mice after aerobic swimming and aerobic swimming+salidroside were detected. The results showed that aerobic swimming and aerobic swimming+salidroside inhibited the decline of heart index, liver index, spleen index and kidney index caused by oxidative aging in mice. Aerobic swimming and aerobic swimming+salidroside increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH) in serum, liver and spleen of oxidative aging mice, and decreased the level of malondialdehyde (MDA). The study also found that aerobic swimming and aerobic swimming+salidroside can reduce the damage of oxidative aging to liver and spleen tissues. Quantitative polymerase chain reaction (qPCR) showed that aerobic swimming and aerobic swimming+salidroside could up-regulate the mRNA expression of CAT, GSH, Cu/Zn-SOD, Mn-SOD and GSH-PX in mouse liver tissue. The results showed that aerobic swimming could effectively inhibit the oxidative aging of mice induced by D-galactose, and the effect of aerobic swimming+salidroside was better than that of aerobic swimming alone. It can be seen that salidroside can enhance the improvement of aerobic swimming on oxidative aging and can be used as a sports supplement.
本研究观察了水杨甙通过加强有氧游泳改善D-半乳糖诱导的小鼠氧化衰老的效果。本研究通过D-半乳糖建立小鼠氧化衰老模型,检测有氧游泳和有氧游泳+水苏糖后氧化衰老小鼠血清和组织中器官指数、组织病理学变化及mRNA表达的变化。结果表明,有氧游泳和有氧游泳+沙利度苷可抑制氧化衰老引起的小鼠心脏指数、肝脏指数、脾脏指数和肾脏指数的下降。有氧游泳和有氧游泳+茜草苷提高了氧化衰老小鼠血清、肝脏和脾脏中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和谷胱甘肽(GSH)的活性,降低了丙二醛(MDA)的水平。研究还发现,有氧游泳和有氧游泳+沙利度苷能减轻氧化衰老对肝脏和脾脏组织的损伤。定量聚合酶链反应(qPCR)显示,有氧游泳和有氧游泳+苷酸可上调小鼠肝组织中CAT、GSH、Cu/Zn-SOD、Mn-SOD和GSH-PX的mRNA表达。结果表明,有氧游泳能有效抑制D-半乳糖诱导的小鼠氧化衰老,有氧游泳+苷元的效果优于单独有氧游泳。由此可见,水杨苷能增强有氧游泳对氧化衰老的改善作用,可作为运动补充剂使用。
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引用次数: 0
Analysis Of Patients' Opinion Of Prescribed Medicines: A Questionnaire - Based Pilot Study In Bulgaria 分析患者对处方药的看法:保加利亚基于问卷的试点研究
Pub Date : 2023-11-27 DOI: 10.32383/appdr/173228
Z. Mitkova, M. Doneva, M. Dimitrova, Petya Nikolova, K. Tachkov, G. Petrova
Evaluation of rational drug utilization (RDU) through WHO indicators is used to provide information about the level of development of national policy and to identify the necessity of further regulatory, patients or healthcare professionals -centered measures. The current study aims to investigatethe patients’ perspective about medicines utilization by implementing the WHO’s "followup" indicators in the Bulgarian practice. A prospective, cross -sectional, online inquiry study was conducted among Bulgarian population. The population above 18 years of age is 5.8 million of people and 400 people sample was considered sufficient with 95% CI. The study methodology is based on a modified version of the WHO "followup" indicators. The total number of answers was 467. The majority of patients aged over 56 years responded that they did not receive enough information about the side effects and interactions of the prescribed medicines and the most often they used the leaflet as a source of information. Most of the patients responded they always check the expiry date (61%), while 23 % of patients check it sometimes. In the group of patients over 65 years, 24% responded that they never check the expiry date. The results of our study suggest that rational medicines utilization is a broader concept depending on patients' knowledge and pharmacists and patients relation. It suggests that there is a need to educate both parties, mainly to increase health literacy and promote general aspects of rational medicines utilization.
通过世界卫生组织的指标对合理用药(RDU)进行评估,可提供有关国家政策发展水平的信息,并确定是否有必要进一步采取以监管、患者或医疗保健专业人员为中心的措施。本研究旨在通过在保加利亚实践中实施世界卫生组织的 "跟踪 "指标,调查患者对药物使用的看法。在保加利亚人口中开展了一项前瞻性、横断面、在线调查研究。保加利亚 18 岁以上人口为 580 万,400 人的样本足以满足 95% CI 的要求。研究方法基于世卫组织 "随访 "指标的修订版。答卷总数为 467 份。大多数 56 岁以上的患者回答说,他们没有获得足够的关于处方药副作用和相互作用的信息,他们最常使用的信息来源是宣传单。大多数患者回答说他们经常查看药品的有效期(61%),23%的患者有时会查看。在 65 岁以上的患者群体中,有 24% 回答说他们从不查看有效期。我们的研究结果表明,合理用药是一个较为宽泛的概念,取决于患者的知识水平以及药剂师和患者之间的关系。这表明,有必要对双方进行教育,主要是提高健康素养和宣传合理用药的一般知识。
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引用次数: 0
Anti-inflammatory, Analgesic, and Gastric Tissue Effects of Lacidipine, Aspirin, and Their Combination 拉西地平、阿司匹林及其复方制剂的抗炎、镇痛和胃组织作用
Pub Date : 2023-11-27 DOI: 10.32383/appdr/172400
Bahar Isik, I. Ates, B. Suleyman, R. Mammadov, S. Bulut, M. Gulaboglu, Adalet Ozcicek, H. Suleyman
The increase in cyclooxygenase-2 (COX-2) activity and the decrease in COX-1 activity were associated with increased intracellular calcium. Lacidipine, a calcium channel blocker, can protect gastric tissue from aspirin-induced damage while potentiating the analgesic and anti-inflammatory properties of aspirin. This study, it was aimed to investigate the anti-inflammatory, analgesic, and gastric tissue effects of using lacidipine and aspirin combination, and separately. (LA). Twenty-four rats were randomly divided into CG (carrageenan control), LCG (carrageenan+lacidipine), ACG (carrageenan+aspirin), and LACG (carrageenan+LA) groups. Lacidipine 4 mg/kg, aspirin 100 mg/kg were given orally to the animals on an empty stomach. ,Carrageenan was injected into the foot paws of rats to induce inflammation and pain. Paw volumes were measured at 0, 1, and 4 hours after carrageenan administration, and paw pain thresholds were measured at 1 and 4 hours. After euthanasia (thiopental sodium, 50 mg/kg), paw and gastric tissues were excised and biochemically analyzed. Gastric tissues were also examined macroscopically. In the paw tissues of animals receiving lacidipine, malondialdehyde (MDA) was lower than in the CG and AG, while total glutathione (tGSH) was higher (p<0.05). Lacidipine inhibited COX-2, but not COX-1 isoenzyme. LA, lacidipine, and aspirin inhibited inflammation and hyperalgesia at 1 and 4 hours, respectively. Lacidipine prevented aspirin-induced COX-1 inhibition and gastric ulcer formation. Lacidipine combined with aspirin may be beneficial in initiating its anti-inflammatory activity early, achieving a potent analgesic effect, and preventing aspirin-induced gastric injury.
环氧化酶-2(COX-2)活性的增加和 COX-1 活性的降低与细胞内钙的增加有关。拉西地平是一种钙通道阻滞剂,可保护胃组织免受阿司匹林引起的损伤,同时增强阿司匹林的镇痛和抗炎作用。本研究旨在探讨拉西地平与阿司匹林联合或单独使用的抗炎、镇痛和胃组织效应。大鼠24 只大鼠被随机分为 CG 组(卡拉胶对照组)、LCG 组(卡拉胶+拉西地平)、ACG 组(卡拉胶+阿司匹林)和 LACG 组(卡拉胶+LA)。动物空腹口服拉西地平 4 毫克/千克、阿司匹林 100 毫克/千克。将卡拉胶注射到大鼠的脚掌中,诱发炎症和疼痛。在注射卡拉胶后的 0、1 和 4 小时测量大鼠脚掌的体积,并在 1 和 4 小时测量脚掌的痛阈值。安乐死(硫喷妥钠,50 毫克/千克)后,切除爪和胃组织并进行生化分析。还对胃组织进行了宏观检查。在接受拉西地平治疗的动物爪组织中,丙二醛(MDA)低于 CG 和 AG,而总谷胱甘肽(tGSH)则高于 CG 和 AG(p<0.05)。拉西地平抑制 COX-2,但不抑制 COX-1 同工酶。LA、拉西地平和阿司匹林分别抑制了1小时和4小时的炎症和痛觉减退。拉西地平可防止阿司匹林诱导的 COX-1 抑制和胃溃疡形成。拉西地平与阿司匹林联用可能有利于尽早启动其抗炎活性,实现强效镇痛效果,并防止阿司匹林诱发的胃损伤。
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引用次数: 0
Skeletal Muscle Type-Dependent Effect of Atorvastatin on FoxO3a and Akt in Hypercholesterolemic Rats 阿托伐他汀对高胆固醇血症大鼠骨骼肌类型依赖性的 FoxO3a 和 Akt 影响
Pub Date : 2023-11-27 DOI: 10.32383/appdr/174241
A. Gawędzka, J. Drąg, M. Knapik-Czajka, Małgorzata Belczyk, Angelika Szafran, Iga Szlachta
Statins are one of the most commonly used lipid-lowering drugs reducing the risk of mortality due to cardiovascular diseases. They are well tolerated and have relatively few side effects which mainly affect skeletal muscle. The impact of statins on skeletal muscle functions depends on the composition of the muscle fibers type. One of the mechanisms of statin-induced myopathy is imbalance between muscle protein synthesis and breakdown.Transcription factor FoxO3a is a key factor regulating muscle protein breakdown. The activity of FoxO3a is regulated namely by phosphorylation via PI3K/Akt pathway. Active, phosphorylated Akt catalyzes the phosphorylation and thus inactivation of FoxO3a. The purpose of our study was to evaluate the effect of atorvastatin on FoxO3a and Akt in different skeletal muscles in rats with diet-induced hypercholesterolemia. Atorvastatin (20 mg/kg b.w./day) or the vehicle was administered orally 21 days. FoxO3a, Akt and their phosphorylated protein levels were assayed by Western blot in gastrocnemius and soleus muscle. Additionally, muscle total protein level and serum CK activity were measured. In the gastrocnemius muscle atorvastatin decreased total FoxO3a and P-FoxO3a levels with no changes in Akt and P-Akt level. In contrast, in soleus muscle atorvastatin did not change the level of P-FoxO3a. However, total FoxO3a and the P-Akt level decreased. Serum CK activity did not change in both muscle under atorvastatin treatment. In conclusion, the results of our study indicate that atorvastatin affects FoxO3a and Akt in a muscle type-dependent manner.
他汀类药物是最常用的降脂药物之一,可降低心血管疾病导致的死亡风险。他汀类药物的耐受性良好,副作用相对较少,主要影响骨骼肌。他汀类药物对骨骼肌功能的影响取决于肌肉纤维的组成类型。他汀类药物诱发肌病的机制之一是肌肉蛋白质合成和分解之间的失衡。FoxO3a 的活性是通过 PI3K/Akt 途径磷酸化来调节的。活跃的磷酸化 Akt 可催化 FoxO3a 的磷酸化,从而使其失活。 我们的研究旨在评估阿托伐他汀对饮食诱导高胆固醇血症大鼠不同骨骼肌中 FoxO3a 和 Akt 的影响。阿托伐他汀(20 毫克/千克体重/天)或载体口服给药 21 天。用 Western 印迹法测定腓肠肌和比目鱼肌中 FoxO3a、Akt 及其磷酸化蛋白水平。此外,还测定了肌肉总蛋白水平和血清 CK 活性。 在腓肠肌中,阿托伐他汀降低了总 FoxO3a 和 P-FoxO3a 水平,而 Akt 和 P-Akt 水平没有变化。相反,在比目鱼肌中,阿托伐他汀没有改变 P-FoxO3a 的水平。然而,FoxO3a总量和P-Akt水平有所下降。在阿托伐他汀治疗下,两块肌肉的血清 CK 活性均无变化。总之,我们的研究结果表明,阿托伐他汀以肌肉类型依赖性的方式影响FoxO3a和Akt。
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Acta Poloniae Pharmaceutica - Drug Research
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