Network pharmacology and experimental validation-based approach to understand the effect and mechanism of Taohong Siwu Decoction against ischemic stroke

小桶 当归 药理学 汤剂 传统医学 血瘀 医学 PI3K/AKT/mTOR通路 雷公藤 信号转导 生物 细胞生物学 转录组 基因 中医药 生物化学 病理 基因表达 替代医学
作者
Lingyu Pan,Can Peng,Lei Wang,Lili Li,Shi Huang,Changyi Fei,Ni Wang,Furui Chu,Daiyin Peng,Xianchun Duan
出处
期刊:Journal of Ethnopharmacology [Elsevier BV]
卷期号:294: 115339-115339 被引量:59
标识
DOI:10.1016/j.jep.2022.115339
摘要

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.
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