Pharmacological Mechanisms Underlying the Therapeutic Effects of Danhong Injection on Cerebral Ischemia.

Yifei Qi,Jun Liu,Yihuai Zou,Lin Chen,Yingying Zhang,Zhong Wang,Baotong Zhang

doi:10.1155/2021/5584809

Abstract

Background Although Danhong injection (DHI) has been proved to be curative, the mechanism of its action against ischemia stroke (IS) is not clear. Here, we explored the therapeutic basis of DHI by network pharmacology. Methods Putative targets and activity scores for each compound in DHI were obtained from the Traditional Chinese Medicine System Pharmacology Database, Encyclopedia of Traditional Chinese Medicine, and Quantitative Structure Activity Relationships. Next, target proteins of IS were identified on GeneCards and CTD. Overlapping targets of DHI associated with IS were acquired via Venn diagram. GO and KEGG pathway analyses were done using WebGestalt. Cytoscape software was used for PPI network construction and hub nodes screening. Several validation studies were carried out by using AutoDock-Vina, label-free mass spectrometry, and transcriptome RNA-sequencing. Results The 37 active compounds and 66 targets were identified. Of these, 26 compounds and 41 targets belonged to diterpenoid quinones (DQs), which is the predominant category based on chemical structure. The results of enrichments analysis show that 8 DQs target proteins associated with IS were involved in several biological processes and signaling pathway such as apoptotic, cell cycle, cellular response to xenobiotic stimulus process, and the PI3K-Akt signaling. Moreover, 3 nodes in core module involved in PI3K-Akt signaling and 1 hub node were identified by PPI network analysis. Finally, the results of molecular docking and label-free mass spectrometry display good effect on hub node regulation in DHI treatment. Conclusions DQs is the predominant category of DHI and play an important role in antiapoptotic activity mediated by modulating PI3K-Akt signaling. Our findings offer insight into future research and clinical applications in IS therapy.

Highlights

Cerebral stroke is the second most leading cause of death and the main cause of disability in worldwide
After screening by pharmacokinetic properties and the Lipinski rule of 5, duplicate removal, and verification on PubChem, 37 active compounds were obtained and the divided into 4 categories: 26 diterpenoid quinones (DQs), 3 terpenes, 2 flavonoids, and 6 others (Figure 2)
Based on chemical structure analysis and network pharmacology, we find DQs are the major category in Danhong injection (DHI) compounds

Summary

Introduction

Cerebral stroke is the second most leading cause of death and the main cause of disability in worldwide. Ese single target therapies are limited by the narrow time window of thrombolysis, hemorrhagic tendency, and high cost [8]. For this reason, novel therapeutic strategies are needed. E results of enrichments analysis show that 8 DQs target proteins associated with IS were involved in several biological processes and signaling pathway such as apoptotic, cell cycle, cellular response to xenobiotic stimulus process, and the PI3K-Akt signaling. 3 nodes in core module involved in PI3K-Akt signaling and 1 hub node were identified by PPI network analysis. The results of molecular docking and label-free mass spectrometry display good effect on hub node regulation in DHI treatment. Our findings offer insight into future research and clinical applications in IS therapy

Methods

Results

Discussion

Conclusion