Xie Feng, Wu Yuan-Yuan, Duan Guang-Jing, Wang Bin, Gao Feng, Wei Pei-Feng, Chen Lin, Liu A-Ping, Li Min
School of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an, China.
Front Pharmacol. 2021 May 6;12:609702. doi: 10.3389/fphar.2021.609702. eCollection 2021.
Dried ginger-aconite decoction (DAD) is a traditional Chinese medicine (TCM) formula that has been extensively used in the treatment of myocardial ischemia reperfusion injury (MI/RI). However, its specific mechanism against MI/RI has not been reported yet. Therefore, this paper studies the potential active components and mechanism of DAD against MI/RI based on network pharmacology and experimental verification. Sixteen active components of DAD were screened according to oral bioavailability and drug similarity indices. Through Cytoscape 3.7.0, a component-target network diagram was drawn, and potential active components of DAD against MI/RI were determined. Protein-protein interaction (PPI) and compound-target-pathway (C-T-P) networks were established through the software to discover the biological processes, core targets and core pathways of DAD against MI/RI. High Performance Liquid Chromatography (HPLC) analysis identified the presence of potentially active core components for network pharmacological prediction in DAD. It was found that DAD might have played a therapeutic role in anti-MI/RI by activating the PI3K/Akt/GSK-3β signaling pathway in order to reduce mitochondrial hypoxia injury and myocardial cell apoptosis. The network pharmacological prediction was validated by Hypoxia/reoxygenation(H/R) model and ligation model of the ligation of the left anterior descending branch . It was verified that DAD had activated PI3K/AKT/GSK-3β to reduce myocardial apoptosis and play a therapeutic function in MI/RI.
干姜附子汤(DAD)是一种传统中药配方,已被广泛用于治疗心肌缺血再灌注损伤(MI/RI)。然而,其抗MI/RI的具体机制尚未见报道。因此,本文基于网络药理学和实验验证研究了DAD抗MI/RI的潜在活性成分和作用机制。根据口服生物利用度和药物相似性指数筛选出DAD的16种活性成分。通过Cytoscape 3.7.0绘制成分-靶点网络图,确定DAD抗MI/RI的潜在活性成分。通过该软件建立蛋白质-蛋白质相互作用(PPI)和化合物-靶点-通路(C-T-P)网络,以发现DAD抗MI/RI的生物学过程、核心靶点和核心通路。高效液相色谱(HPLC)分析确定了DAD中存在用于网络药理学预测的潜在活性核心成分。研究发现,DAD可能通过激活PI3K/Akt/GSK-3β信号通路发挥抗MI/RI的治疗作用,以减少线粒体缺氧损伤和心肌细胞凋亡。通过缺氧/复氧(H/R)模型和左前降支结扎模型验证了网络药理学预测。证实DAD激活PI3K/AKT/GSK-3β可减少心肌细胞凋亡,并在MI/RI中发挥治疗作用。