Long Linzi, Yu Zikai, Qu Hua, Wang Ning, Guo Ming, Zhou Xuezhong, Fu Changgeng, Gao Zhuye
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350112, China.
Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Evid Based Complement Alternat Med. 2020 Apr 22;2020:8574702. doi: 10.1155/2020/8574702. eCollection 2020.
This study investigated whether saponins (PNS) reduced atherosclerotic lesion formation in apolipoprotein E knockout (ApoE-KO) mice and illustrated the potential mechanism for a network pharmacology approach. Pharmacodynamics studies on ApoE-KO mice with atherosclerosis (AS) showed that PNS generated an obvious anti-AS action. Then, we explored the possible mechanisms underlying its anti-AS effect using the network pharmacology approach. The main chemical components and their targets of PNS were collected from TCMSP public database and SymMap. The STRING v11.0 was used to establish the protein-protein interactions of PNS. Furthermore, the Gene Ontology (GO) function and KEGG pathways were analyzed using STRING to investigate the possible mechanisms involved in the anti-AS effect of PNS. The predicted results showed that 27 potential targets regulated by DSLHG were related to AS, including ACTA2, AKT1, BCL2, and BDNF. Mechanistically, the anti-AS effect of PNS was exerted by interfering with multiple signaling pathways, such as AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, and TNF signaling pathway. Network analysis showed that PNS could generate the anti-AS action by affecting multiple targets and multiple pathways and provides a novel basis to clarify the mechanisms of anti-AS of PNS.
本研究调查了三七总皂苷（PNS）是否能减少载脂蛋白E基因敲除（ApoE-KO）小鼠的动脉粥样硬化病变形成，并阐明了网络药理学方法的潜在机制。对动脉粥样硬化（AS）的ApoE-KO小鼠进行的药效学研究表明，PNS具有明显的抗AS作用。然后，我们使用网络药理学方法探索其抗AS作用的潜在机制。从中药系统药理学数据库与分析平台（TCMSP）公共数据库和SymMap收集PNS的主要化学成分及其靶点。使用STRING v11.0建立PNS的蛋白质-蛋白质相互作用。此外，使用STRING分析基因本体论（GO）功能和KEGG通路，以研究参与PNS抗AS作用的可能机制。预测结果表明，由PNS调控的27个潜在靶点与AS相关，包括平滑肌肌动蛋白2（ACTA2）、蛋白激酶B1（AKT1）、B细胞淋巴瘤-2（BCL2）和脑源性神经营养因子（BDNF）。机制上，PNS的抗AS作用是通过干扰多种信号通路发挥的，如晚期糖基化终末产物-受体（AGE-RAGE）信号通路、流体切应力与动脉粥样硬化以及肿瘤坏死因子（TNF）信号通路。网络分析表明，PNS可通过影响多个靶点和多条通路产生抗AS作用，为阐明PNS抗AS机制提供了新的依据。
