Systematic Understanding of the Mechanism of Baicalin against Ischemic Stroke through a Network Pharmacology Approach.

Tian Xu,Weizhe Du,Fafeng Cheng,Shuling Liu,Ling Tan,Zhenhan Li,Yajun Lian,Beida Ren,Shuang Zhang,Xueqian Wang,Nang Deng,Qinguo Wang,Shuning Fan,Chongyang Ma

doi:10.1155/2018/2582843

Abstract

Ischemic stroke is accompanied by high mortality and morbidity rates. At present, there is no effective clinical treatment. Alternatively, traditional Chinese medicine has been widely used in China and Japan for the treatment of ischemic stroke. Baicalin is a flavonoid extracted from Scutellaria baicalensis that has been shown to be effective against ischemic stroke; however, its mechanism has not been fully elucidated. Based on network pharmacology, we explored the potential mechanism of baicalin on a system level. After obtaining baicalin structural information from the PubChem database, an approach combined with literature mining and PharmMapper prediction was used to uncover baicalin targets. Ischemic stroke-related targets were gathered with the help of DrugBank, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). Protein-protein interaction (PPI) networks were constructed through the Cytoscape plugin BisoGenet and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. We obtained a total of 386 potential targets and 5 signaling pathways, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), hypoxia-inducible factor-1 (HIF-1), nuclear factor kappa B (NF-κB), and forkhead box (FOXO) signaling pathways. GO analysis showed that these targets were associated with antiapoptosis, antioxidative stress, anti-inflammation, and other physiopathological processes that are involved in anti-ischemic stroke effects. In summary, the mechanism of baicalin against ischemic stroke involved multiple targets and signaling pathways. Our study provides a network pharmacology framework for future research on traditional Chinese medicine.

Highlights

A stroke is a common medical condition among adults worldwide, characterized by high mortality, morbidity, and disability rates [1]
With the help of Traditional Chinese Medicine Systems Pharmacology (TCMSP), we found some important information related to ADME, such as human OB, DL, Caco-2 permeability, blood-brain barrier (BBB) permeability, and Lipinski’s rule of five (MW, AlogP, TPSA, Hdon, and Hacc)
ADME-related properties of baicalin were inspected by TCMSP comprehensively and, in particular, the DL of baicalin was calculated as 0.75, indicating that baicalin is similar to known drugs (Supplementary Table 1)

Summary

Introduction

A stroke is a common medical condition among adults worldwide, characterized by high mortality, morbidity, and disability rates [1]. The two major therapeutic strategies for ischemic stroke are thrombolytic therapy and neuroprotective therapy [4]. Recombinant tissue plasminogen activator (rtPA) is the only compound approved by the Food and Drug Administration as an effective strategy against acute ischemic stroke [5]. Due to time window limitations and other difficulties, potential drugs for ischemic stroke treatment are urgently required. It is well known that multiple pathologic processes are involved in ischemic stroke, including energy metabolism and oxidative stress that vary as the ischemia-reperfusion injury progresses [6].

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Results

Conclusion