Abstract
Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained. Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR. Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05). Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.
Highlights
Cerebrovascular disease is a common disease in the clinic, which seriously endangers human health and life
The prediction results of systematic pharmacology showed that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) can regulate cerebral ischemia-reperfusion injury (CIR)-related targets, biological processes and signaling pathways
The experiments showed that HCC can improve the neurological deficit score, decrease the Abbreviations: CIR, cerebral ischemia-reperfusion injury; DL, drug-likeness; GO, Gene Ontology; HCC, Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound; HPLC, high performance liquid chromatography; Ischemia-reperfusion injury (IRI), Ischemiareperfusion injury; MVD, microvessel density; NMDA, N-methyl-D-aspartic acid; OB, oral bioavailability; PPI, protein-protein interaction; Reverse TranscriptionPolymerase Chain Reaction (RT-PCR), Reverse Transcription-Polymerase Chain Reaction; traditional Chinese Medicine (TCM), traditional Chinese medicine; TNF, tumor necrosis factor; TXB2, thromboxane B2
Summary
Cerebrovascular disease is a common disease in the clinic, which seriously endangers human health and life. The key to cerebral ischemia treatment is to quickly restore cerebral blood perfusion and maintain smooth blood flow (Frizzell, 2005; Behravan et al, 2014). The brain injury may be further aggravated after the restoration of blood flow perfusion, that is cerebral ischemia-reperfusion injury (CIR). Ischemia-reperfusion injury (IRI) refers to the pathological phenomenon that the degree of tissue damage is increased after the blood supply to the ischemic tissue is restored for a certain period of time (Wu et al, 2018). It involves many complicated links and factors, which has been the focus of scientists’ research for many years. Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). Its mechanism for treating cerebral ischemia is still not fully explained
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