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Percepción de los medicamentos genéricos en pobladores en un distrito del Perú 秘鲁一个地区居民对仿制药的看法
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 DOI: 10.56499/jppres23.1658_11.6.1114
Ambrocio Teodoro Esteves Pairazaman, José Rincón Chávez, Consuelo Berta Horna Sandoval, Flor Lidia Bustamante Fustamante, Yolanda Ruiz Vargas
Context: In the Peruvian context, generic drugs are those pharmaceutical products whose names correspond to the active ingredient of the drug and are not identified by a brand name; brand name drugs, on the other hand, are pharmaceutical products whose names are determined by the drug manufacturer. Aims: To know the perception of generic drugs by a Peruvian population. Methods: The type of research was applied, deductive method, non-experimental design, quantitative approach and cross-sectional. The sample consisted of 218 inhabitants, who were submitted to a questionnaire where the study variable was measured. Results: The main results showed that the level of information on generic drugs among the study sample was low (74,3%), as was consumption (66,5%), the level of confidence in these drugs was low (64,7%) and, finally, the inhabitants indicated that they had little access to generic drugs in their area (68,8%). Conclusions: The general perception of the study population towards generic drugs was low.
背景:在秘鲁背景下,仿制药是那些药品的名称与药物的活性成分相对应,没有品牌名称;另一方面,品牌药品是由药品制造商确定名称的药品。目的:了解秘鲁人群对仿制药的认知。方法:采用类型研究法、演绎法、非实验设计法、定量法和横断面法。样本由218名居民组成,他们提交了一份调查问卷,其中测量了研究变量。结果:研究对象对仿制药的了解程度较低(74.3%),对仿制药的消费量较低(66.5%),对仿制药的置信度较低(64.7%),居民表示他们所在地区获得仿制药的机会很少(68.8%)。结论:研究人群对仿制药的总体认知度较低。
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引用次数: 0
Analysis of factors affecting enoxaparin effectiveness on coagulation, inflammation, and clinical outcomes in patients with COVID-19 影响依诺肝素对COVID-19患者凝血、炎症及临床结局疗效的因素分析
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 DOI: 10.56499/jppres23.1683_11.6.1106
Budi Suprapti, Liana Debora, Rifdah Atikah Safitri, Dewi Kusumawati, Arina Dery Puspitasari
Context: Hypercoagulopathy is a COVID-19 extra-pulmonary manifestation has drawn the attention of the scientists due to its risk of thromboembolism. Enoxaparin is an anticoagulant used to prevent hypercoagulopathy. Many factors have been associated with enoxaparin effectiveness. Aims: To analyze factors affecting enoxaparin effectiveness on coagulation, inflammation, and clinical outcomes. Methods: This retrospective cohort study involved hospitalized adult patients with COVID-19 from November 2020 to April 2021. Patients’ age, gender, body mass index (BMI), comorbidity, and laboratory results were extracted from medical records. Factors influencing enoxaparin efficacy on coagulation, inflammation, and clinical outcomes were analyzed using path analysis with SmartPLS 3.0 software. D-dimer and platelet values was determined as coagulation outcomes and C-reactive protein (CRP) value as an inflammation outcome. Clinical outcomes comprised of mortality, ventilator usage, and length of stay. Results: A total of 269 patients fulfilled the inclusion criteria. Most of the subjects were male (58%), 66% had comorbidities, 48.3% were aged ≥60 years old, and 65.8% had a BMI ≥ 25 kg/m2. Path analysis showed that age, BMI, and comorbidity affected disease severity (p<0.05). Disease severity strongly influenced enoxaparin dosage (p=0.000). Dosage affected platelet value, ventilator usage, and mortality (p<0.05). Gender did not influence disease severity, and dosage displayed no significant effect on length of stay, CRP, and D-dimer (p>0.05). Conclusions: Dosage is the main factor influencing enoxaparin efficacy on coagulation, inflammation, and clinical outcomes. The dosage is strongly affected by disease severity, in which is predominantly influenced by age, BMI, and comorbidity.
背景:高凝血病是新冠肺炎的肺外表现,由于其血栓栓塞的风险引起了科学家的注意。依诺肝素是一种用于预防高凝病的抗凝剂。许多因素与依诺肝素的有效性有关。目的:分析影响依诺肝素治疗凝血、炎症及临床预后的因素。方法:本回顾性队列研究纳入2020年11月至2021年4月住院的成年COVID-19患者。从医疗记录中提取患者的年龄、性别、体重指数(BMI)、合并症和实验室结果。采用SmartPLS 3.0软件进行通径分析,分析影响依诺肝素凝血、炎症及临床结局的因素。d -二聚体和血小板值作为凝血结果,c反应蛋白(CRP)值作为炎症结果。临床结果包括死亡率、呼吸机使用和住院时间。结果:269例患者符合纳入标准。大多数受试者为男性(58%),66%有合并症,48.3%年龄≥60岁,65.8% BMI≥25 kg/m2。通径分析显示,年龄、BMI和合并症影响疾病严重程度(p < 0.05)。疾病严重程度强烈影响依诺肝素剂量(p=0.000)。剂量影响血小板值、呼吸机使用和死亡率(p < 0.05)。性别对疾病严重程度无影响,剂量对住院时间、CRP和d -二聚体无显著影响(p < 0.05)。结论:剂量是影响依诺肝素凝血、消炎及临床疗效的主要因素。剂量受疾病严重程度的强烈影响,其中主要受年龄、BMI和合并症的影响。
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引用次数: 0
The analysis of coffee-green tea-turmeric combination against cardiac-metabolic syndrome using metabolite profiling, gene expression, and in silico approach 利用代谢物谱、基因表达和计算机方法分析咖啡-绿茶-姜黄组合对心脏代谢综合征的作用
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 DOI: 10.56499/jppres23.1702_11.6.961
Ermin Rachmawati, Mohammad S. Rohman, Nashi Widodo, Mifetika Lukitasari, Dwi A. Nugroho, Feri E. Hermanto, Mukhamad N. Kholis
Context: The development of functional drinks to inhibit oxidative stress and inflammation as a critical process in inducing heart damage in metabolic syndrome is required. Coffee, tea, and turmeric have all been shown to offer health advantages. Aims: To investigate the effect of coffee, green tea, turmeric extract (ECGTT) against cardiac-metabolic syndrome (MetS). Methods: The secondary metabolites from coffee, green tea, and turmeric were identified using LC-HRMS. Male Sprague–Dawley rats were divided into four groups (n = 4) representing normal, MetS, MetS with ECGTT treatment doses: 300/100/150 mg/BW and 300/100/250 mg/BW group. Upon the end of treatment periods, expression of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), NADPH oxidase (NOX2), SERCA2a were measured from the heart. A computational approach including network pharmacology, protein-protein interaction (PPI) network, molecular docking, and dynamic was performed to understand the molecular mechanism of ECGTT against cardiac damage in MetS. Results: Chlorogenic acid (CGA), epigallocatechin gallate (EGCG), and curcumin were identified as the main metabolites in ECGTT. The ECGTT administration decreased the TNFα, IL-6, NF-κB, and NOX2 and increased SERCA2a expression(p<0.05). Moreover, the PPI result suggested that angiotensin II receptor type 1 (AGTR1) was the key regulator of cardiac injury-MetS induced. CGA, EGCG, and curcumin bind to AGTR1 with smaller binding energy than metformin and showed stability of structure and interaction among those metabolites into AGTR1. Conclusions: Coffee, green tea, and turmeric might prevent heart dysfunction in MetS through modulation of oxidative stress and inflammation.
背景:需要开发功能饮料来抑制氧化应激和炎症,这是代谢综合征诱导心脏损伤的关键过程。咖啡、茶和姜黄都被证明对健康有益。目的:探讨咖啡、绿茶、姜黄提取物(ECGTT)对心脏代谢综合征(MetS)的影响。方法:采用液相色谱质谱法对咖啡、绿茶和姜黄的次生代谢产物进行鉴定。雄性Sprague-Dawley大鼠分为4组(n = 4),分别为正常组、MetS组、MetS组,ECGTT治疗剂量分别为300/100/150 mg/BW组和300/100/250 mg/BW组。治疗结束后,检测肿瘤坏死因子- α (TNFα)、白细胞介素-6 (IL-6)、核因子κB (NF-κB)、NADPH氧化酶(NOX2)、SERCA2a的表达。通过网络药理学、蛋白-蛋白相互作用(PPI)网络、分子对接和动力学等计算方法,了解ECGTT抗MetS心脏损伤的分子机制。结果:ECGTT主要代谢产物为绿原酸(CGA)、没食子儿茶素没食子酸酯(EGCG)和姜黄素。ECGTT使TNFα、IL-6、NF-κB、NOX2表达降低,SERCA2a表达升高(p < 0.05)。此外,PPI结果提示血管紧张素II受体1型(AGTR1)是mets诱导的心脏损伤的关键调节因子。与二甲双胍相比,CGA、EGCG和姜黄素以更小的结合能与AGTR1结合,并表现出结构稳定性和与AGTR1相互作用。结论:咖啡、绿茶和姜黄可能通过调节氧化应激和炎症来预防MetS患者的心脏功能障碍。
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引用次数: 0
SLCO1B1 and CYP3A4 allelic variants associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru: Clinical implications 在秘鲁使用的辛伐他汀和阿托伐他汀与药代动力学相互作用和不良反应相关的SLCO1B1和CYP3A4等位基因变异:临床意义
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 DOI: 10.56499/jppres23.1686_11.6.934
Angel T. Alvarado, Ana María Muñoz, Roberto O. Ybañez-Julca, Mario Pineda-Pérez, Nesquen Tasayco-Yataco, María R. Bendezú, Jorge A. García, Felipe Surco-Laos, Haydee Chávez, Doris Laos-Anchante, Aura Molina-Cabrera, Carmela Ferreyra-Paredes, Nelly Vega-Ramos, Patricia Castillo-Romero, Javier Chávez-Espinoza, Juan Panay-Centeno, Eliades Yarasca-Carlos
Context: Statins reduce the risk of stroke and prevent cardiac events in people with atherosclerosis and diabetes mellitus; and could affect the proliferation, migration, and survival of cancer cells. Aims: To review the most up-to-date and available scientific evidence on the allelic variants of SLCO1B1 and CYP3A4 associated with pharmacokinetic interactions and adverse reactions induced by simvastatin and atorvastatin used in Peru, and their clinical implications. Methods: The bibliographic search was carried out in the PubMed/Medline, Google Scholar and Science Direct databases. The keywords were: “statin”, “atorvastatin”, “simvastatin” in combination with “pharmacokinetics”, “pharmacogenetics”, “CYP3A4”, “SLCO1B1” or “drug interactions” considering the eligibility criteria defined by the PRISMA-2020 international statement. Results: Scientific evidence indicates a significant association between SLCO1B1 rs4149056 c.521T>C (521CC and 521TC) and increased plasma levels, area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) of simvastatin, compared to wild-type SLCO1B1*1/*1 521TT (p<0.05). SLCO1B1 521C is not associated with atorvastatin (p>0.05). Patients with SLCO1B1 521CC had a significantly higher risk of myopathy and rhabdomyolysis induced by simvastatin compared to TT (p<0.05). An association was also found between CYP3A4*1/*22/CYP3A4*3/*22 and increased pharmacokinetic parameters of simvastatin compared to CYP3A4*1/*1 (p< 0.05). Conclusions: Based on the review of the published scientific evidence, it is concluded that individuals carrying the allelic variants SLCO1B1 (c.521T>C), CYP3A4*1/*22 and CYP3A4*3/*22 could be associated with an increase in the pharmacokinetic parameters and with an increased risk of myopathy and rhabdomyolysis induced by simvastatin, and not by atorvastatin.
背景:他汀类药物可降低动脉粥样硬化和糖尿病患者中风和预防心脏事件的风险;并可能影响癌细胞的增殖、迁移和存活。目的:回顾秘鲁使用的SLCO1B1和CYP3A4等位基因变异与辛伐他汀和阿托伐他汀的药代动力学相互作用和不良反应相关的最新和现有的科学证据及其临床意义。方法:在PubMed/Medline、Google Scholar和Science Direct数据库中进行文献检索。关键词是:“他汀类”、“阿托伐他汀”、“辛伐他汀”联合“药代动力学”、“药物遗传学”、“CYP3A4”、“SLCO1B1”或“药物相互作用”,考虑到PRISMA-2020国际声明定义的资格标准。结果:科学证据表明,与野生型SLCO1B1*1/*1 521TT相比,SLCO1B1 rs4149056 C . 521t >C (521CC和521TC)与辛伐他汀血药浓度升高、血药浓度曲线下面积(AUC)和最大血药浓度(Cmax)显著相关(p < 0.05)。SLCO1B1 521C与阿托伐他汀无关(p>0.05)。SLCO1B1 521CC患者发生辛伐他汀诱导的肌病和横纹肌溶解的风险明显高于TT (p < 0.05)。与CYP3A4*1/*1相比,CYP3A4*1/*22/CYP3A4*3/*22与辛伐他汀增加的药代动力学参数之间也存在关联(p<0.05)。结论:基于已发表的科学证据,我们得出结论,携带SLCO1B1 (C . 521t >C)、CYP3A4*1/*22和CYP3A4*3/*22等位基因变异的个体可能与辛伐他汀而非阿托伐他汀诱导的药代动力学参数升高、肌病和横纹肌分解的风险增加有关。
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引用次数: 0
Hepatoprotective study of Indonesian water kefir against CCl4-induced liver injury in rats 印尼水开菲尔对ccl4致大鼠肝损伤的保护作用研究
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-01 DOI: 10.56499/jppres23.1732_11.6.1002
Widhya Aligita, Marlia Singgih, Entris Sutrisno, I Ketut Adnyana
Context: Water kefir is a fermented beverage that is typically made in the home by inoculating a sugar-rich solution with a microbial community (water kefir grains). Several studies on the metabolite content and hepatoprotective effects of water kefir have been published, but carbon tetrachloride (CCl4)-induced acute liver injury has not been studied. Aims: To evaluate the efficacy of water kefir in vivo against hepatoprotective CCl4-induced acute liver injury and to in silico investigate metabolites that play an important role in hepatoprotective mechanisms. Methods: The present study aimed to investigate the hepatoprotective activity of water kefir in an animal model caused by CCl4. Furthermore, using molecular docking, the metabolites found in water kefir were evaluated for their role in the NF-κB and Nrf2 signaling pathways. Results: Water kefir significantly and dose-dependently alleviated acute liver injury caused by CCl4. Water kefir administration at all doses produced results comparable to the positive control (Curcuma extract). Molecular docking simulations showed that, compared to Nrf2, the 25 metabolites were more likely to interact with the NF-B receptor. Fumaric acid is the strong metabolite that interacts with the NF-κB receptor with a free energy of binding and an inhibition constant of -6.66 kcal/mol and 13.22 µM, respectively. Conclusions: Water kefir administration improved the condition of liver damage, characterized by a decrease in serum levels of AST, ALT, TNF-, TGF-, and an improvement in the liver tissue profile. In silico evaluation showed that the metabolites in water kefir were able to interact with target proteins in the NF-B and Nrf2 pathways. It was concluded that water kefir improves the condition of the liver by reducing the level of necrosis and fibrosis.
背景:水开菲尔是一种发酵饮料,通常在家中通过接种富含糖的溶液和微生物群落(水开菲尔颗粒)制成。一些关于水开菲尔代谢物含量和肝保护作用的研究已经发表,但尚未研究四氯化碳(CCl4)诱导的急性肝损伤。目的:评价水开非尔在体内对ccl4诱导的急性肝损伤的保护作用,探讨在肝保护机制中起重要作用的代谢产物。方法:研究水开菲尔对CCl4致小鼠肝保护作用。此外,通过分子对接,我们评估了水开菲尔中发现的代谢物在NF-κB和Nrf2信号通路中的作用。结果:水开非尔可显著减轻CCl4所致急性肝损伤,且具有剂量依赖性。所有剂量的水开菲尔管理产生的结果与阳性对照(姜黄提取物)相当。分子对接模拟显示,与Nrf2相比,这25种代谢物更可能与NF-B受体相互作用。富马酸是与NF-κB受体相互作用的强代谢物,其自由结合能和抑制常数分别为-6.66 kcal/mol和13.22µM。结论:水开非尔可改善肝损伤状况,其特征是血清AST、ALT、TNF-、TGF-水平降低,肝组织形态改善。计算机评价表明,水开菲尔的代谢物能够通过NF-B和Nrf2途径与靶蛋白相互作用。由此可见,水开菲尔通过降低肝脏坏死和纤维化水平来改善肝脏状况。
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引用次数: 0
Risk factors for oral cancer: Thematic trends and research agenda 口腔癌的危险因素:专题趋势和研究议程
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 DOI: 10.56499/jppres23.1712_11.5.887
Orlando Pérez-Delgado, Pablo Alejandro Millones-Gómez, Alejandro Valencia-Arias, David Yeret Rodríguez-Salazar
Context: Oral cancer is difficult to define due to several factors. It's known as oral squamous cell carcinoma (OSCC) and is common in the head and neck. Geographic variations in the impact of OSCC highlight the need for research on risk factors and treatment trends. Aims: To identify the main research trends of studies on oral cancer risk factors in the scientific literature in the Scopus database and Web of Science. Methods: This was an exploratory study of the risk factors for oral cancer designed considering the eligibility criteria defined by the PRISMA-2020 international statement, that is, inclusion and exclusion. Results: A total of 215 documents from Scopus and Web of Science were subjected to bibliometric analysis. The years 2020 and 2021 were the most productive, with 18 and 22 articles, respectively. The leading author in productivity and impact was Johnson N, the leading journal was Oral Oncology, followed by the International Journal of Cancer, and the main contributing countries were the United States, the United Kingdom and India. The main thematic cluster was composed of concepts such as Tobacco and Alcohol as the major risk factors; concepts such as Mortality or Head and Neck were positioned as emerging within the scientific literature. Conclusions: The main risk factors, i.e., alcohol and tobacco consumption, are relevant in terms of mortality in the consumer population, which is why their role should be determined in future studies.
背景:口腔癌是难以定义的,由于几个因素。它被称为口腔鳞状细胞癌(OSCC),常见于头部和颈部。OSCC影响的地理差异突出了对风险因素和治疗趋势进行研究的必要性。目的:了解Scopus数据库和Web of Science科学文献中口腔癌危险因素研究的主要研究趋势。方法:本研究是一项针对口腔癌危险因素的探索性研究,根据PRISMA-2020国际标准定义的纳入和排除标准设计。结果:对来自Scopus和Web of Science的215篇文献进行文献计量学分析。2020年和2021年的产量最高,分别为18篇和22篇。生产力和影响力方面的主要作者是Johnson N,领先的期刊是口腔肿瘤学,其次是国际癌症杂志,主要贡献国是美国,英国和印度。主要专题组由以下概念组成:烟草和酒精是主要风险因素;诸如死亡率或头颈等概念在科学文献中被定位为新兴概念。结论:主要的危险因素,即酒精和烟草消费,在消费人群的死亡率方面是相关的,这就是为什么它们的作用应该在未来的研究中确定。
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引用次数: 0
Improvement of spermatozoa concentration due to maximal exercise with Vitis gracilis Wall. 用薄壁葡萄进行最大强度运动对精子浓度的改善。
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 DOI: 10.56499/jppres23.1685_11.5.874
Syafruddin Ilyas, Putra Santoso, Yurnadi Hanafi Midoen, Putri Cahaya Situmorang
Context: Swimming is a common form of exercise; however, excessive exercise might reduce sperm count by lowering testosterone levels and increasing the production of free radicals, commonly known as reactive oxygen species (ROS). In Indonesia, Vitis gracilis Wall. is a traditional remedy for increasing stamina. Aims: To assess the concentration of spermatozoa after vigorous physical activity and V. gracilis administration, as well as the histological and apoptotic changes in testicular histology that occur via caspase-3 expression. Methods: This study was conducted on six groups of rats: the control group (G+), a group of rats subjected to vigorous swimming then administered 0.2 mg/kg BW vit C (GVitC), and three groups of rats subjected to vigorous swimming then administered 100, 125, or 150 mg/kg BW V. gracilis (G100, G125, and G150). Testicular tissue and blood serum samples were extracted from the rats subjected to vigorous swimming. Testicular tissue was immunohistochemically stained using caspase-3 antibody and TUNEL assays, while blood samples were analysed using ELISA. Results: V. gracilis administration significantly affected IL-6 and testosterone levels (p<0.00). Testosterone had a greater impact on spermatozoa concentration than IL-6. Caspase-3 expression and the proportion of apoptotic cells were both markedly reduced. Conclusions: Administering 125 mg/kg BW V. gracilis can help to increase sperm concentration by reducing apoptosis through altering caspase-3 and IL-6 levels, thereby preventing inflammation. This plant might be a viable molecular therapeutic target for staminal medicines.
背景:游泳是一种常见的运动形式;然而,过度运动可能会通过降低睾丸激素水平和增加自由基的产生来减少精子数量,自由基通常被称为活性氧(ROS)。在印度尼西亚,这是一种葡萄树。是提高耐力的传统疗法。目的:观察剧烈运动和给药后精子浓度的变化,以及通过caspase-3表达对睾丸组织和细胞凋亡的影响。方法:本研究采用6组大鼠进行实验:对照组(G+),剧烈游泳组给予0.2 mg/kg BW的维生素C (GVitC),剧烈游泳组给予100、125、150 mg/kg BW的股细筋(G100、G125、G150)。从剧烈游泳大鼠身上提取睾丸组织和血清样本。用caspase-3抗体和TUNEL法对睾丸组织进行免疫组织化学染色,同时用ELISA法对血液样本进行分析。结果:股薄草组显著影响IL-6和睾酮水平(p<0.00)。睾酮对精子浓度的影响大于IL-6。Caspase-3表达及凋亡细胞比例均明显降低。结论:给药125 mg/kg体重可通过改变caspase-3和IL-6水平减少精子凋亡,从而提高精子浓度,从而预防炎症。该植物可能是一种可行的药物分子治疗靶点。
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引用次数: 0
Antimalarial and toxicological assessment of the tablet (AS201-01) ethyl acetate fraction of Andrographis paniculata Nees in animal models 穿心莲醋酸乙酯片AS201-01抗疟及动物毒理学评价
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 DOI: 10.56499/jppres23.1679_11.5.863
Aty Widyawaruyanti, Hilkatul Ilmi, Lidya Tumewu, Dwi Ayu Fitrianingtyas, Yesinta Kurniawati, Alfin Laila Najiha, Hanifah Khairun Nisa, Che Puteh Osman, Nor Hadiani Ismail, Achmad Fuad Hafid
Context: Andrographis paniculata has been used as a traditional medicine to treat malaria. The ethyl acetate fraction of A. paniculata containing diterpene lactone compounds was developed into a tablet dosage form, AS201-01. Aims: To determine the antimalarial activity and toxicity of AS201-01 to guarantee its efficacy and safety. Methods: Antimalarial assay in male Balb/c mice based on Peter’s four-day suppressive test at a dose of 6.25, 12.5, 25, and 50 mg/kg BW and 10 mg/kg BW of chloroquine as a positive control. In acute toxicity, AS201-01 was administered orally at a dose of 5, 50, 200, and 2,000 mg/kg BW in male rats (Wistar rats) and observed for 14 days to identify signs of toxicity and mortality. Meanwhile, AS201-01 was administered at 50, 327, and 1,000 mg/kg BW per day for 28 days in male and female rats to assess subchronic toxicity. Results: AS201-01 has antimalarial activity and exhibited the highest suppressive effect at 50 mg/kg BW dose with inhibition of 73.48%. Meanwhile, chloroquine at 10 mg/kg BW has an inhibition of 97.94%. AS201-01 was highly active as an antimalarial with an ED50 value of 5.95 mg/kg BW and increased survival time. Administration of AS201-01 is relatively safe in acute and subchronic toxicity studies. No clinical signs and mortality were observed in either study. The 50% lethal dose (LD50) was above 2,000 mg/kg BW. Conclusions: AS201-01 is effective as an antimalarial and non-toxic when administered orally at an equivalent therapeutic dose in an animal model.
背景:穿心莲一直被用作治疗疟疾的传统药物。将含二萜内酯化合物的金针叶乙酸乙酯部分研制成片剂AS201-01。目的:测定AS201-01的抗疟活性和毒性,保证其有效性和安全性。方法:采用Peter 4天抑制实验,分别给Balb/c雄性小鼠6.25、12.5、25、50 mg/kg BW和10 mg/kg BW氯喹作为阳性对照,进行抗疟试验。在急性毒性试验中,AS201-01分别以5、50、200和2000 mg/kg BW的剂量口服雄性大鼠(Wistar大鼠),观察14天,以确定毒性和死亡迹象。同时,将AS201-01分别以50、327和1000 mg/kg BW / d的剂量给药于雄性和雌性大鼠,连续28天评估其亚慢性毒性。结果:AS201-01具有抗疟活性,当剂量为50 mg/kg BW时,抑制率最高,为73.48%。氯喹浓度为10 mg/kg BW时,抑制率为97.94%。AS201-01抗疟活性高,ED50值为5.95 mg/kg BW,可延长存活时间。AS201-01在急性和亚慢性毒性研究中相对安全。两项研究均未观察到临床症状和死亡率。50%致死剂量(LD50)在2000 mg/kg BW以上。结论:AS201-01在动物模型中以等效治疗剂量口服时是有效的抗疟药物,并且无毒。
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引用次数: 0
In silico targeting CYP51 of Naegleria fowleri using bioactive compounds from Indonesian plants 利用印尼植物活性化合物靶向福氏奈格丽虫CYP51的研究
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 DOI: 10.56499/jppres23.1693_11.5.841
Nelson Daniel, Fisranda Ferdinand, Parikesit Arli Aditya
Context: Given the elusive nature of Primary Amoebic Meningoencephalitis (PAM), caused by Naegleria fowleri, early detection is vital, yet challenging due to limited clinical indicators. This research leverages Indonesia's rich biodiversity to explore novel sources of traditional medicine. Aims: To evaluate the potential compounds from Indonesian plants that possess antiamoebic and antifungal properties for inhibiting the N. fowleri CYP51 protein, crucial for cell integrity. Methods: Initially, 92 compounds were screened, and six were shortlisted following ADMETox evaluation. Subsequent steps encompassed QSAR analysis, molecular docking, and molecular dynamics simulations. Results: The QSAR analysis verified the activity potential of these six compounds, progressing them to molecular docking analysis. Among these, curcumenol from Curcuma longa emerged as a promising contender, displaying the lowest binding affinity at -9.2 kcal/mol, indicative of superior binding compared to other ligands. Molecular dynamics simulations underscored the stability of all compounds, with root mean square fluctuation (RMSF) values within 1-3 Å. Conclusions: Consequently, employing a comprehensive approach spanning ADMETox, QSAR, molecular docking, and dynamics simulations, curcumenol emerged as the prime candidate for inhibiting the N. fowleri CYP51 protein, suggesting its potential as a PAM therapeutic agent.
背景:由于福氏奈格里杆菌引起的原发性阿米巴脑膜脑炎(PAM)难以捉摸,早期发现至关重要,但由于临床指标有限,具有挑战性。这项研究利用印度尼西亚丰富的生物多样性来探索传统医学的新来源。目的:评价印尼植物中具有抗阿米巴和抗真菌特性的潜在化合物,以抑制对细胞完整性至关重要的福氏奈氏菌CYP51蛋白。方法:最初筛选92个化合物,经ADMETox评估后,6个化合物入围。随后的步骤包括QSAR分析、分子对接和分子动力学模拟。结果:QSAR分析验证了这6个化合物的活性势,将其推进到分子对接分析。其中,姜黄烯醇的结合亲和力最低,为-9.2 kcal/mol,与其他配体相比具有较强的结合能力。分子动力学模拟强调了所有化合物的稳定性,均方根波动(RMSF)值在1-3 Å之间。结论:因此,通过ADMETox、QSAR、分子对接和动力学模拟等综合方法,姜黄酚成为抑制福氏奈氏菌CYP51蛋白的主要候选者,表明其作为PAM治疗剂的潜力。
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引用次数: 0
Synthesis and in vitro activity tests of N-benzoyl-N'-phenylthiourea derivatives as macrophage migration inhibitory factor 巨噬细胞迁移抑制因子n -苯甲酰- n′-苯基硫脲衍生物的合成及体外活性试验
Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-09-01 DOI: 10.56499/jppres23.1657_11.5.902
Dini Kesuma, Galih S. Putra, Tegar A. Yuniarta, Farida Suhud, I G.A. Sumartha, Sawitri Boengas, Melanny I. Sulistyowaty, Tjie Kok
Context: The COVID-19 pandemic in 2020 resulted in widespread mortalities due to cytokine storms in the affected patients. Macrophage migration inhibitory factor (MIF) is one of the most interesting targets in developing anti-COVID-19 drugs. Some thiourea compounds have been identified as having potential as MIF inhibitors. Aims: To investigate MIF inhibitory activity of N-benzoyl-N'-phenylthiourea derivatives. Methods: The study consists of in-silico activity prediction of designed compounds using a molecular docking approach against MIF protein (PDB ID: 1LJT). Afterwards, the designed compounds were synthesized and tested in vitro using the tautomerase activity approach. Results: The molecular docking study showed that all designed compounds possess comparable docking scores to the native ligand of the protein. MIF Assay performed on compounds (1) and (2) indicated a decrease in tautomerase activity of the MIF target protein of only 10.1 and 6.2%, respectively, compared to the positive control. Conclusions: In silico results predicted better bioactivity against MIF protein, but the result does not translate to the in vitro assay, where two of the designed compounds possess only low inhibitory activity.
背景:2020年的COVID-19大流行导致受影响患者因细胞因子风暴而广泛死亡。巨噬细胞迁移抑制因子(Macrophage migration inhibitory factor, MIF)是抗covid -19药物开发中最有趣的靶点之一。一些硫脲化合物已被确定为具有潜在的MIF抑制剂。目的:研究n -苯甲酰- n′-苯基硫脲衍生物对MIF的抑制作用。方法:采用分子对接方法对设计的化合物进行MIF蛋白(PDB ID: 1LJT)的硅活性预测。随后,合成了设计的化合物,并利用互变异构酶活性法进行了体外测试。结果:分子对接研究表明,所有设计的化合物与蛋白质的天然配体具有相当的对接分数。对化合物(1)和(2)进行的MIF实验表明,与阳性对照相比,MIF靶蛋白的变异体酶活性分别下降了10.1%和6.2%。结论:计算机实验结果预测了对MIF蛋白更好的生物活性,但结果不能转化为体外实验,其中两种设计的化合物仅具有低抑制活性。
{"title":"Synthesis and in vitro activity tests of N-benzoyl-N'-phenylthiourea derivatives as macrophage migration inhibitory factor","authors":"Dini Kesuma, Galih S. Putra, Tegar A. Yuniarta, Farida Suhud, I G.A. Sumartha, Sawitri Boengas, Melanny I. Sulistyowaty, Tjie Kok","doi":"10.56499/jppres23.1657_11.5.902","DOIUrl":"https://doi.org/10.56499/jppres23.1657_11.5.902","url":null,"abstract":"Context: The COVID-19 pandemic in 2020 resulted in widespread mortalities due to cytokine storms in the affected patients. Macrophage migration inhibitory factor (MIF) is one of the most interesting targets in developing anti-COVID-19 drugs. Some thiourea compounds have been identified as having potential as MIF inhibitors. Aims: To investigate MIF inhibitory activity of N-benzoyl-N'-phenylthiourea derivatives. Methods: The study consists of in-silico activity prediction of designed compounds using a molecular docking approach against MIF protein (PDB ID: 1LJT). Afterwards, the designed compounds were synthesized and tested in vitro using the tautomerase activity approach. Results: The molecular docking study showed that all designed compounds possess comparable docking scores to the native ligand of the protein. MIF Assay performed on compounds (1) and (2) indicated a decrease in tautomerase activity of the MIF target protein of only 10.1 and 6.2%, respectively, compared to the positive control. Conclusions: In silico results predicted better bioactivity against MIF protein, but the result does not translate to the in vitro assay, where two of the designed compounds possess only low inhibitory activity.","PeriodicalId":43917,"journal":{"name":"Journal of Pharmacy & Pharmacognosy Research","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135255124","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
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Journal of Pharmacy & Pharmacognosy Research
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