The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
J Ethnopharmacol. 2022 Aug 10;294:115339. doi: 10.1016/j.jep.2022.115339. Epub 2022 May 5.
Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine that is mainly used for promoting blood circulation and alleviating blood stasis. THSWD is composed of Prunus persica (L.) Batsch, Carthamus tinctorius L., Ligusticum chuanxiong hort, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa (Gaertn.) DC, and Paeoniae Radix Alba. This prescription eliminates blood stasis, supplements blood, and dredges the body as an auxiliary treatment.
To investigate the mechanistic effects of THSWD in the treatment of cerebral ischemia.
we downloaded 39 blood components for THSWD from the PharmMapper database for target prediction studies and identified the targets of cerebral ischemia. We identified the intersection between the components and targets, constructed a protein-protein interaction (PPI) network, carried out GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. a rat model of cerebral ischemia was established in rats, and the results of network pharmacology were verified by in vivo experiments.
Established a component-target-pathway network, further transcriptomics analysis identified a total of 11 target genes (Plau, Fabp4, Mmp9, Mmp12, Cfd, Lcn2, Trem1, Lgals3, Hmox1, Selp and Slc6a4), a total of seven pathways (focal adhesion, complement and coagulation cascades, Staphylococcus aureus infection, malaria, transcriptional dysregulation in cancer, progesterone-mediated oocyte maturation, and the PI3K-Akt signaling pathway), because both targets genes and the complement and coagulation cascade signaling pathways mediate inflammatory responses, the signaling pathways associated with the complement and coagulation cascades were selected for experimental verification. We detected inflammatory factors and several key proteins in the complement and coagulation cascade signaling pathway (C1qb, C1qc, C3ar1, C5ar1, and Cfd). Analysis showed that THSWD can reduce the release of inflammatory factors and inhibit activation of the complement signaling pathways, thereby protecting against ischemic stroke disease.
Our findings provide preliminary clarification of the predominant mechanism of action of THSWD when used to treat ischemic stroke.
桃红四物汤（THSWD）是一种经典的中药方剂，主要用于活血化瘀。THSWD 由桃仁、红花、川芎、当归、熟地黄和白芍组成。该方剂具有活血化瘀、补血、通络的功效，可作为辅助治疗手段。
研究桃红四物汤治疗脑缺血的作用机制。
从 PharmMapper 数据库中下载了 39 种桃红四物汤的血液成分进行靶标预测研究，并鉴定了脑缺血的靶标。我们鉴定了成分和靶标的交集，构建了蛋白质-蛋白质相互作用（PPI）网络，并进行了 GO 和京都基因与基因组百科全书（KEGG）富集分析。建立了大鼠脑缺血模型，通过体内实验验证了网络药理学的结果。
建立了一个成分-靶标-通路网络，进一步的转录组学分析共鉴定出 11 个靶基因（Plau、Fabp4、Mmp9、Mmp12、Cfd、Lcn2、Trem1、Lgals3、Hmox1、Selp 和 Slc6a4），共 7 条通路（黏附斑、补体和凝血级联、金黄色葡萄球菌感染、疟疾、癌症转录失调、孕激素介导的卵母细胞成熟和 PI3K-Akt 信号通路），由于靶基因和补体和凝血级联信号通路都介导炎症反应，因此选择与补体和凝血级联信号通路相关的信号通路进行实验验证。我们检测了炎症因子和补体和凝血级联信号通路中的几个关键蛋白（C1qb、C1qc、C3ar1、C5ar1 和 Cfd）。分析表明，桃红四物汤可以减少炎症因子的释放，抑制补体信号通路的激活，从而起到防治缺血性中风的作用。
本研究结果初步阐明了桃红四物汤治疗缺血性中风的主要作用机制。
