PDF(Pubmed)
Abstract：
Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. Quercetin plays a significant role in neuroinflammation, which helps reduce Alzheimer\'s disease (AD) severity. Quercetin (Q) and quercetin 3-O-glucuronide (Q3OG) are some of the most potent antioxidants available from natural sources. However, the natural form of quercetin converted into Q3OG when reacted with intestinal microbes. The study aims to ensure the therapeutic potential of Q and Q3OG. In this study, potential molecular targets of Q and Q3OG were first identified using the Swiss Target Prediction platform and pathogenic targets of AD were identified using the DisGeNET database. Followed by compound and disease target overlapping, 77 targets were placed in that AKT1, EGFR, MMP9, TNF, PTGS2, MMP2, IGF1R, MCL1, MET and PARP1 was the top-ranked target, which was estimated by CytoHubba plug-in. The Molecular docking was performed for Q and Q3OG towards the PDB:1UNQ target. The binding score of Q and Q3OG was - 6.2 kcal/mol and - 6.58 kcal/mol respectively. Molecular dynamics simulation was conducted for Q and Q3OG towards the PDB:1UNQ target at 200 ns. This study\'s results help identify the multiple target sites for the bioactive compounds. Thus, synthesizing new chemical entity-based quercetin on structural modification may aid in eradicating AD complications.
摘要：
槲皮素是一种黄酮类化合物，具有显着的药理作用和有前途的治疗潜力。槲皮素在神经炎症中起重要作用，这有助于降低阿尔茨海默病（AD）的严重程度。槲皮素（Q）和槲皮素3-O-葡糖苷酸（Q3OG）是一些从天然来源获得的最有效的抗氧化剂。然而,当与肠道微生物反应时，槲皮素的天然形式转化为Q3OG。该研究旨在确保Q和Q3OG的治疗潜力。在这项研究中,首先使用SwissTargetPrediction平台鉴定Q和Q3OG的潜在分子靶标,并使用DisGeNET数据库鉴定AD的致病靶标。其次是化合物和疾病靶点重叠，77个靶点被置于AKT1、EGFR、MMP9,TNF,PTGS2,MMP2,IGF1R,MCL1、MET和PARP1是排名第一的目标，这是CytoHubba插件估计的。针对Q和Q3OG朝向PDB:1UNQ靶标进行分子对接。Q和Q3OG的结合评分分别为-6.2kcal/mol和-6.58kcal/mol。在200ns下对Q和Q3OG朝向PDB:1UNQ目标进行分子动力学模拟。这项研究的结果有助于确定生物活性化合物的多个靶位点。因此，通过结构修饰合成基于化学实体的槲皮素可能有助于根除AD并发症.
