Meng Qingwen, Liu Huajiang, Wu Haolin, Shun Ding, Tang Chaoling, Fu Xinyin, Fang Xingyue, Xu Yiqian, Chen Bocen, Xie Yiqiang, Liu Qibing
Deparment of Vasculocardiology, The First Affiliated Hospital of Hainan Medical University, Haikou 570100, China.
Department of Pharmacology, Hainan Medical University, Haikou 570100, China.
Evid Based Complement Alternat Med. 2022 May 14;2022:3242015. doi: 10.1155/2022/3242015. eCollection 2022.
Safflower has long been used to treat coronary heart disease (CHD). However, the underlying mechanism remains unclear. The goal of this study was to predict the therapeutic effect of safflower against CHD using a network pharmacology and to explore the underlying pharmacological mechanisms. Firstly, we obtained relative compounds of safflower based on the TCMSP database. The TCMSP and PubChem databases were used to predict targets of these active compounds. Then, we built CHD-related targets by the DisGeNET database. The protein-protein interaction (PPI) network graph of overlapping genes was obtained after supplying the common targets of safflower and CHD into the STRING database. The PPI network was then used to determine the top ten most significant hub genes. Furthermore, the DAVID database was utilized for the enrichment analysis on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To validate these results, a cell model of CHD was established in EAhy926 cells using oxidized low-density lipoprotein (ox-LDL). Safflower was determined to have 189 active compounds. The TCMSP and PubChem databases were used to predict 573 targets of these active compounds. The DisGeNET database was used to identify 1576 genes involved in the progression of CHD. The top ten hub genes were , and . GO functional enrichment analysis yielded 92 entries for biological process (BP), 47 entries for cellular component (CC), 31 entries for molecular function (MF), and 20 signaling pathways, which were obtained from KEGG pathway enrichment screening. Based on these findings, the FoxO signaling pathway is critical in the treatment of CHD by safflower. The in vitro results showed that safflower had an ameliorating effect on ox-LDL-induced apoptosis and mitochondrial membrane potential. The western blot results showed that safflower decreased Bax expression and acetylation of FoxO1 proteins while increasing the expression of Bcl-2 and SIRT1 proteins. Safflower can be used in multiple pathways during CHD treatment and can exert anti-apoptotic effects by regulating the expression of Bax, Bcl-2, and SIRT1/FoxO1 signaling pathway-related proteins.
红花长期以来一直用于治疗冠心病（CHD）。然而，其潜在机制仍不清楚。本研究的目的是利用网络药理学预测红花对冠心病的治疗效果，并探索其潜在的药理机制。首先，我们基于中药系统药理学数据库（TCMSP）获得了红花的相关化合物。利用TCMSP和美国国立医学图书馆的化学物质数据库（PubChem）预测这些活性化合物的靶点。然后，我们通过疾病基因数据库（DisGeNET）构建了冠心病相关靶点。将红花和冠心病的共同靶点输入搜索工具检索相互作用基因的数据库（STRING）后，获得了重叠基因的蛋白质-蛋白质相互作用（PPI）网络图。然后利用PPI网络确定十大最显著的枢纽基因。此外，利用DAVID数据库对基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行富集分析。为了验证这些结果，使用氧化型低密度脂蛋白（ox-LDL）在人脐静脉内皮细胞系EAhy926中建立了冠心病细胞模型。确定红花有189种活性化合物。利用TCMSP和PubChem数据库预测这些活性化合物的573个靶点。DisGeNET数据库用于鉴定1576个参与冠心病进展的基因。十大枢纽基因为 ，以及 。GO功能富集分析产生了92个生物过程（BP）条目、47个细胞成分（CC）条目、31个分子功能（MF）条目和20条信号通路，这些是从KEGG通路富集筛选中获得的。基于这些发现，叉头框O（FoxO）信号通路在红花治疗冠心病中至关重要。体外实验结果表明，红花对ox-LDL诱导的细胞凋亡和线粒体膜电位具有改善作用。蛋白质免疫印迹结果表明，红花降低了促凋亡蛋白Bax的表达和叉头框蛋白O1（FoxO1）蛋白的乙酰化水平，同时增加了抗凋亡蛋白B细胞淋巴瘤/白血病-2（Bcl-2）和沉默调节蛋白1（SIRT1）的表达。红花可在冠心病治疗的多个途径中发挥作用，并可通过调节Bax、Bcl-2以及SIRT1/FoxO1信号通路相关蛋白的表达发挥抗凋亡作用。
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