Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology

Abstract

Background. Ischemic stroke (IS) is a serious disease with a high rate of death and disability, and a growing number of people are becoming victims. Existing drugs not only have limited therapeutic effects but also have obvious side effects. Most importantly, drug resistance due to long-term or improper use of drugs is detrimental to patients. Therefore, it is urgent to find some alternative or supplementary medicines to alleviate the current embarrassment. Powerful Tianma Eucommia Capsule (PTEC) is mainly used to treat IS in China for thousands of years; however, the molecular mechanism is not clear. Methods. Pharmacology ingredients and target genes were filtered and downloaded from websites. A pharmacology ingredient-target gene network was constructed to predict the molecular interactions between ingredients and target genes. Enrichment analysis was performed to explore the possible signal pathways. LeDock was used to simulate the interaction form between proteins and main active ingredients and to deduce key amino acid positions. Results. Two hundred eighty-nine target genes and seventy-four pharmacological ingredients were obtained from public databases. Several key ingredients (quercetin, kaempferol, and stigmasterol) and primary core target genes (PTGS1, NCOA2, and PRSS1) were detected through ingredient-target gene network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that ingredients affect networks mainly in nuclear receptor activity and G protein-coupled amine receptor activity; besides, fluid shear stress and atherosclerosis, human cytomegalovirus infection, and hepatitis B signaling pathways might be the principal therapy ways. A series of presumed key amino acid sites (189ASP, 190SER, 192GLN, 57HIS, and 99TYE) were calculated in PRSS1. Six of the target genes were differentially expressed between male and female patients. Conclusions. Seven new putative target genes (ACHE, ADRA1A, AR, CHRM3, F7, GABRA1, and PRSS1) were observed in this work. Based on the result of GO and KEGG analysis, this work will be helpful to further demonstrate the molecular mechanism of PTEC treatment of IS.

Study on the mechanism of Qiju Dihuang pill in the treatment of ophthalmic diseases based on systems pharmacology

“…[ 20 ] Besides, target proteins like ADRA1A, CHRM1, and HTR2C are mainly affected G protein-coupled amine receptor activity, affecting immune regulation. [ 20 ]…”

“…[19] At the same time, the targets can also affect the growth and reproduction of corneal epithelial cells. [20] Besides, target proteins like ADRA1A, CHRM1, and HTR2C are mainly affected G protein-coupled amine receptor activity, affecting immune regulation. [20] Table 1 The top 20 bioactive compounds with their OB and DL values.…”

“…[20] Besides, target proteins like ADRA1A, CHRM1, and HTR2C are mainly affected G protein-coupled amine receptor activity, affecting immune regulation. [20] Table 1 The top 20 bioactive compounds with their OB and DL values. Neuronal acetylcholine receptor subunit alpha-7 P36544…”

Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

“…Formononetin is able to recover injured nerve functions by enhancing synaptic plasticity, downregulating of the Bax/ Bcl-2 ratio, and upregulating PI3K/Akt signaling pathway in the treatment of CIS 35,36 . Baicalein exerts a neuroprotective effect against ischemic/reperfusion injury via alteration of NF-κB, LOX, and AMPK/Nrf2 signaling pathway 37 . Arachidonic acid can play a neuroprotective role after cerebral infarction by reducing oxidative stress 38 .…”