Network Pharmacology-Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood-Brain Barrier.

Shuang Zhang,Kai Lv,Na Jin,Wenxiu Xu,Chongyang Ma,Fafeng Cheng,Qingguo Wang,Shuning Fan,Xueqian Wang,Shuling Liu

doi:10.1155/2020/2914579

Abstract

Ischemic stroke is the most common type of cerebrovascular accident worldwide. It causes long-term disability and death. Qingkailing (QKL) injection is a traditional Chinese patent medicine which has been clinically applied in the treatment of ischemic stroke for nearly thirty years. In the present study, network pharmacology combined with experimentation was used to elucidate the mechanisms of QKL. ADME screening and target prediction identified 62 active compounds and 275 targets for QKL. Topological screening of the protein-protein interaction (PPI) network was used to build a core PPI network consisting of 408 nodes and 17,830 edges. KEGG enrichment indicated that the main signaling pathway implicated in ischemic stroke involved hypoxia-inducible factor-1 (HIF-1). Experimentation showed that QKL alleviated neurological deficits, brain infraction, blood-brain barrier (BBB) leakage, and tight junction degeneration in a mouse ischemic stroke model. Two-photon laser scanning microscopy was used to evaluate BBB permeability and cerebral microvessel structure in living mice. HIF-1α, matrix metalloproteinase-9 (MMP-9), and tight junction proteins such as occludin, zonula occludins-1 (ZO-1), claudin-5, and VE-Cadherin were measured by western blotting. QKL upregulated ZO-1 and downregulated HIF-1α and MMP-9. QKL has a multiapproach, multitarget, and synergistic effect against ischemic stroke.

Highlights

Stroke is a major cause of long-term disability and death worldwide
To evaluate QKL anti-ischemic stroke efficiency, we used a transient middle cerebral arterial occlusion (tMCAO) mouse model to mimic cerebral ischemia and reperfusion injury. e brain infarct volume was examined by TTC staining at 24 h
Screening of the Active Compounds in QKL and Constructing of Compound-Target Network. e active compounds in QKL had to be screened in order to elucidate its underlying mechanisms of ischemic stroke treatment

Summary

Introduction

Stroke is a major cause of long-term disability and death worldwide. Despite the stable morbidity of stroke and the decline in its mortality over the past decade, the absolute numbers of incidences and disability-adjusted life-years associated with it are rising. The global burden of stroke may increase as the population ages [1]. Ischemic stroke is the most common type of cerebrovascular accident. It accounts for approximately 80% of all types of strokes [2]. It is the result of the thromboembolic occlusion of a major cerebral artery or its branches [3]. Treatment of ischemic stroke with intravenous thrombolysis is limited by a short therapeutic time window, incomplete recanalization, hemorrhagic transformation, and reperfusion injury [3]

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Discussion

Conclusion