Exploring the mechanism of Radix Rhei Et Rhizome intervention in intracerebral hemorrhage based on systematic pharmacology and proteomics strategy.

Xiaofei Zhu,Kailin Yang,Tingting Bao,Liang Liu,Zhiyong Long

doi:10.1042/bsr20201910

Abstract

Objective: To explore the mechanism of Radix Rhei Et Rhizome (Dahuang, DH) intervention in intracerebral hemorrhage (ICH) based on systematic pharmacology and proteomics strategy.Methods: The systematic pharmacological strategies were utilized to find the bioactive compounds of Radix Rhei Et Rhizome, predict its potential targets, and collect ICH’s disease genes; then, the Cytoscape 3.7.1 software was applied for network construction and network topology analysis. After that, in-depth analysis of the proteomics data of Radix Rhei Et Rhizome intervention in ICH was performed to complement and validate the results of systematic pharmacological predictions.Results: A total of three major networks were constructed in the present study: (1) compound–compound target network of Radix Rhei Et Rhizome, (2) DH-ICH PPI network, (3) proteomics proteins’ PPI network. These three major networks have been analyzed by network topology, and several small networks derived (such as signaling pathway networks). The enrichment analysis showed that Radix Rhei Et Rhizome can intervene in several biological process (such as inflammation, smooth muscle proliferation, platelet activation, blood pressure regulation, angiogenesis, hypoxia, and inflammatory response of leukocytes), signaling pathway (such as FoxO signaling pathway, complement and coagulation cascades, cGMP-PKG signaling pathway, and Rap1 signaling pathway), and reactome pathway (such as signaling by interleukins, interleukin-4 and interleukin-13 signaling, nuclear receptor transcription pathway, and platelet activation).Conclusion: Radix Rhei Et Rhizome may intervene in ICH-related biological process, signaling pathway, and reactome pathway found in this research so as to achieve the effect of treating ICH related injuries.

Highlights

Intracerebral hemorrhage (ICH) refers to bleeding result from non-traumatic rupture of blood vessels in the brain parenchyma, accounting for 25–30% of all strokes
The ICH-related brain injury can be divided into two categories (ICH primary brain injury and ICH secondary brain injury) due to different mechanisms
Secondary injuries occur within minutes after the onset of ICH, and can last for several days or even months, which is an important factor leading to cell death in the brain and long-term neurological damage [6]

Summary

Introduction

Intracerebral hemorrhage (ICH) refers to bleeding result from non-traumatic rupture of blood vessels in the brain parenchyma, accounting for 25–30% of all strokes. ICH primary brain injury is brain parenchymal injury mediated by the hematoma mechanical occupying effect [3,4]. The secondary damage of ICH is mainly due to the strong cytotoxicity of metabolites (including thrombin, hemoglobin, heme, and iron overload, and so on) during the dissolution of hematomas on adjacent brain cells, which triggers inflammatory reactions and oxidative stress, and causes brain edema and damage to the blood–brain barrier, eventually leading to cell damage and death [4,5]. Surgery can only relieve the mechanical compression of intracranial hematomas, and has no obvious improvement effect on secondary injuries. There is no effective treatment method for secondary injuries. Secondary injuries occur within minutes after the onset of ICH, and can last for several days or even months, which is an important factor leading to cell death in the brain and long-term neurological damage [6]

Methods

Results

Conclusion