Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Medicine (Baltimore). 2024 Sep 13;103(37):e39598. doi: 10.1097/MD.0000000000039598.
We conducted network pharmacology and molecular docking analyses, and executed in vitro experiments to assess the mechanisms and prospective targets associated with the bioactive components of Bombyx batryticatus in the treatment of diabetic kidney disease (DKD). The bioactive components and potential targets of B batryticatus were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Using 5 disease databases, we conducted a comprehensive screening of potential disease targets specifically associated with DKD. Common targets shared between the bioactive components and disease targets were identified through the use of the R package, and subsequently, a protein-protein interaction network was established using data from the STRING database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses pertaining to the identified common targets were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Molecular docking simulations involving the bioactive components and their corresponding targets were modeled through AutoDock Vina and Pymol. Finally, to corroborate and validate these findings, experimental assays at the cellular level were conducted. Six bioactive compounds and 142 associated targets were identified for B batryticatus. Among the 796 disease targets associated with DKD, 56 targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the involvement of these shared targets in diverse biological processes and signaling pathways, notably the PI3K-Akt signaling pathway. Molecular docking analyses indicated a favorable binding interaction between quercetin, the principal bioactive compound in B batryticatus, and RAC-alpha serine/threonine-protein kinase. Subsequently, in vitro experiments substantiated the inhibitory effect of quercetin on the phosphorylation level of PI3K and Akt. The present study provides theoretical evidence for a comprehensive exploration of the mechanisms and molecular targets by which B batryticatus imparts protective effects against DKD.
我们进行了网络药理学和分子对接分析，并进行了体外实验，以评估与蚕茧治疗糖尿病肾病（DKD）相关的生物活性成分的机制和潜在靶点。蚕茧的生物活性成分和潜在靶点来源于中药系统药理学数据库和分析平台。使用 5 种疾病数据库，我们全面筛选了与 DKD 特异性相关的潜在疾病靶点。通过使用 R 包，确定了生物活性成分和疾病靶点之间的共同靶点，然后使用 STRING 数据库中的数据建立了蛋白质-蛋白质相互作用网络。使用数据库进行鉴定的共同靶点的基因本体论和京都基因与基因组百科全书富集分析用于注释、可视化和综合发现。涉及生物活性成分及其相应靶标的分子对接模拟通过 AutoDock Vina 和 Pymol 进行建模。最后，为了证实和验证这些发现，在细胞水平上进行了实验。确定了蚕茧的 6 种生物活性化合物和 142 个相关靶点。在与 DKD 相关的 796 个疾病靶点中，确定了 56 个靶点。基因本体论和京都基因与基因组百科全书途径分析表明，这些共享靶点参与了多种生物学过程和信号通路，特别是 PI3K-Akt 信号通路。分子对接分析表明，蚕茧中的主要生物活性化合物槲皮素与 RAC-alpha 丝氨酸/苏氨酸蛋白激酶之间存在有利的结合相互作用。随后，体外实验证实了槲皮素对 PI3K 和 Akt 磷酸化水平的抑制作用。本研究为全面探讨蚕茧对 DKD 的保护作用的机制和分子靶点提供了理论依据。
