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Bioinformatics and experimental findings reveal the therapeutic actions and targets of pachymic acid against cystitis glandularis
Biofactors ( IF 5.0 ) Pub Date : 2021-04-24 , DOI: 10.1002/biof.1734
Zihao Feng 1 , Hailin Shi 1 , Bojian Liang 1 , Tianyu Ge 1 , Menghui Cai 1 , Feng Liu 1 , Kunping Huang 1 , Jintao Wen 1 , Qiuhong Chen 1 , Bo Ge 1
Affiliation  

Pachymic acid (PA), a bioactive ingredient isolated from Poria cocos Wolf, is reported with potential benefits of anti-inflammatory, anti-oxidative actions. It is reasoned that PA may play the potential benefits against cystitis glandularis (CG), an inflammation of the bladder tissue. In this study, we aimed to apply the network pharmacology and molecular docking analyses to reveal concrete anti-CG targets and mechanisms of PA, and then the bioinformatic findings were verified by using clinical and animal samples. The methodological data from network pharmacology approach showed that 303 and 243 reporting targets of CG and PA, and other 31 shared targets of CG and PA were identified. Subsequently, all top targets of PA against CG were screened out, including cyclooxygenase-2, epidermal growth factor receptor, tumor antigen p53 (TP53), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) beta, proto-oncogene c-jun. Molecular docking data demonstrated that PA exerted potent bonding capacities with TNF, TP53 proteins in CG. In human study, the findings suggested that overactivated TNF-α expression and suppressed TP53 activation were detected in CG samples. In animal study, PA-treated mice showed reduced intravesical IL-1, IL-6 levels, and lactate dehydrogenase content, downregulated TNF-α and upregulated TP53 proteins in bladder samples. Taken together, our bioinformatics and experimental findings identify the key anti-CG biotargets and mechanisms of PA. More markedly, these pivotal pharmacological targets of PA against CG have been screened out and verified by using computational and experimental analyses.

中文翻译:

生物信息学和实验结果揭示了茯苓酸对腺性膀胱炎的治疗作用和靶点

茯苓酸 (PA),一种从茯苓中分离出的生物活性成分,据报道具有抗炎、抗氧化作用的潜在益处。有理由认为 PA 可能对腺性膀胱炎 (CG) 发挥潜在益处,这是一种膀胱组织的炎症。在本研究中,我们旨在应用网络药理学和分子对接分析来揭示 PA 的具体抗 CG 靶点和机制,然后通过临床和动物样本验证生物信息学研究结果。来自网络药理学方法的方法学数据显示,确定了 303 个和 243 个 CG 和 PA 的报告目标,以及其他 31 个 CG 和 PA 的共享目标。随后,筛选出所有 PA 抗 CG 的顶级靶点,包括环氧合酶-2、表皮生长因子受体、肿瘤抗原 p53(TP53)、肿瘤坏死因子-α(TNF)、白介素-1(IL-1)β、原-癌基因c-jun。分子对接数据表明,PA 与 CG 中的 TNF、TP53 蛋白具有强大的结合能力。在人体研究中,研究结果表明在 CG 样本中检测到过度活化的 TNF-α 表达和抑制的 TP53 活化。在动物研究中,经 PA 处理的小鼠显示膀胱内 IL-1、IL-6 水平和乳酸脱氢酶含量降低,膀胱样本中 TNF-α 下调和 TP53 蛋白上调。总之,我们的生物信息学和实验结果确定了 PA 的关键抗 CG 生物靶点和机制。更明显的是,这些 PA 对 CG 的关键药理靶点已通过计算和实验分析筛选出来并得到验证。研究结果表明,在 CG 样本中检测到过度活化的 TNF-α 表达和抑制的 TP53 活化。在动物研究中,经 PA 处理的小鼠显示膀胱内 IL-1、IL-6 水平和乳酸脱氢酶含量降低,膀胱样本中 TNF-α 下调和 TP53 蛋白上调。总之,我们的生物信息学和实验结果确定了 PA 的关键抗 CG 生物靶点和机制。更明显的是,这些 PA 对 CG 的关键药理靶点已通过计算和实验分析筛选出来并得到验证。研究结果表明,在 CG 样本中检测到过度活化的 TNF-α 表达和抑制的 TP53 活化。在动物研究中,经 PA 处理的小鼠显示膀胱内 IL-1、IL-6 水平和乳酸脱氢酶含量降低,膀胱样本中 TNF-α 下调和 TP53 蛋白上调。总之,我们的生物信息学和实验结果确定了 PA 的关键抗 CG 生物靶点和机制。更明显的是,这些 PA 对 CG 的关键药理靶点已通过计算和实验分析筛选出来并得到验证。总之,我们的生物信息学和实验结果确定了 PA 的关键抗 CG 生物靶点和机制。更明显的是,这些 PA 对 CG 的关键药理靶点已通过计算和实验分析筛选出来并得到验证。总之,我们的生物信息学和实验结果确定了 PA 的关键抗 CG 生物靶点和机制。更明显的是,这些 PA 对 CG 的关键药理靶点已通过计算和实验分析筛选出来并得到验证。
更新日期:2021-04-24
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