Department of Pharmacology, Xinjiang Medical University, 830011 Urumqi, Xinjiang, China.
Department of Pharmacy, Urumqi Maternal and Child Health Care Hospital, 830011 Urumqi, Xinjiang, China.
Biomed Res Int. 2022 Dec 24;2022:9494548. doi: 10.1155/2022/9494548. eCollection 2022.
L. (OBL) is mainly used to treat neurological diseases in China. The preliminary work of this group showed that OBL improves cognitive impairment in Alzheimer's disease (AD). However, the underlying pharmacological mechanism remains unclear.
The components of OBL were compiled by literature search, and their active ingredients were screened by online database. The drug targets of OBL in the treatment of AD were predicted and analyzed using information derived from sources such as the SwissTargetPrediction tool. And through the network visual analysis function of Cytoscape software and protein-protein interaction analysis (PPI), the core targets of OBL treatment of AD are predicted. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by OBL. Moreover, AutoDock software was used to assess the potential binding affinity between the core targets and the active compounds. Subsequently, experiment was conducted to verify the findings of network pharmacology.
A total of 35 active compounds and 188 targets of OBL were screened, of which 43 common targets were related to AD. The active compounds of 35 OBLs induced 118 GO and 78 KEGG. The results of PPI and network topology parameter analysis show that targets such as MAPK1, GSK3B, NR3C2, ESR1, and EGFR are known as the core targets for the treatment of AD by OBL and are docked with the active ingredients of OBL. Molecular docking results suggest that diterbutyl phthalate (DBP) may be the main active component of OBL for the treatment of AD. Flow cytometry analysis results showed that apoptosis decreased with increasing DBP dose. In addition, DBP significantly decreased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in the supernatant of A -induced injury HT22 cell cultures, and it can be speculated that DBP has the ability to protect the stability of injured neuronal cells and improve the permeability of cell membranes, thus stabilizing the intracellular environment. Mechanistically, DBP may increase the mRNA levels of AKT, GSK-3, etc. in AD cell models and regulate the phosphorylation of AKT/GSK-3 pathway-related.
Conclusively, our study suggests that DBP, the main active component of OBL, has potential in the prevention or treatment of AD.
灯盏乙素（L.，OBL）主要用于治疗中国的神经疾病。本研究小组的初步工作表明，OBL 可改善阿尔茨海默病（AD）的认知障碍。然而，其潜在的药理机制尚不清楚。
通过文献检索编写 OBL 的成分，并通过在线数据库筛选其活性成分。使用瑞士靶点预测工具等来源的信息，预测和分析 OBL 治疗 AD 的药物靶点。并通过 Cytoscape 软件的网络可视化分析功能和蛋白质-蛋白质相互作用分析（PPI），预测 OBL 治疗 AD 的核心靶点。此外，采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析 OBL 相关信号通路。而且，使用 AutoDock 软件评估核心靶标与活性化合物之间的潜在结合亲和力。随后，进行实验验证网络药理学的研究结果。
筛选出 35 种 OBL 活性化合物和 188 个靶点，其中 43 个共同靶点与 AD 相关。35 种 OBL 活性化合物诱导 118 个 GO 和 78 个 KEGG。PPI 和网络拓扑参数分析的结果表明，MAPK1、GSK3B、NR3C2、ESR1 和 EGFR 等靶点被认为是 OBL 治疗 AD 的核心靶点，并与 OBL 的活性成分对接。分子对接结果表明，邻苯二甲酸二丁酯（DBP）可能是 OBL 治疗 AD 的主要活性成分。流式细胞术分析结果表明，随着 DBP 剂量的增加，凋亡减少。此外，DBP 显著降低了 A 诱导损伤 HT22 细胞培养上清液中乳酸脱氢酶（LDH）和活性氧（ROS）的水平，因此可以推测 DBP 具有保护损伤神经元细胞稳定性和改善细胞膜通透性的能力，从而稳定细胞内环境。机制上，DBP 可能会增加 AD 细胞模型中 AKT、GSK-3 等的 mRNA 水平，并调节 AKT/GSK-3 通路相关的磷酸化。
总之，我们的研究表明，OBL 的主要活性成分 DBP 可能具有预防或治疗 AD 的潜力。
