| Ischemic stroke is a complex disease caused by thrombotic infarction in the main arteries of the brain.It has been the second leading cause of human death and has a high disability rate in patients,which seriously affects the quality of life of the middle-aged and elderly population.Traditional Chinese medicine Dragon's blood(DB)is often used in the treatment of thrombotic diseases,especially in the prognosis of ischemic stroke.Its standard phenolic extract has been used as a medicine for the prognosis of ischemic stroke and is widely used in China.However,the potential mechanisms are still unclear,due to the multi-molecularity and multi-target of traditional Chinese medicine.This study used a systematic pharmacological analysis method to discover the DB's potential molecular mechanisms in prognostic therapy of ischemic stroke,providing a new medication idea for the clinical to ischemic stroke treatment.Systematic pharmacological methods(1)Screening out the potential active molecules of DB according to the biological process of the drug ADME(absorption,distribution,metabolism,excretion).(2)Candidate targets that can be related by DB's active compounds were obtained using a systemic pharmacological target prediction method.The Metascape database was used to cluster the obtained targets and enrich the biological processes of the targets.The TCMSP and CTD databases were combined to obtain the target-related diseases and to establish molecular-targets-disease network(3)Based on Metascape and DAVID databases,enriched the pathways involved in targeting proteins and constructed “ischemic stroke pathways” to analyze the mechanism of DB in treating ischemic stroke.(4)Pharmacodynamic validation at cell levels:PC12 cells are used to explore the protective effect of loureirin B on glucose deprivation/reperfusion(OGD/R)injury and BV-2 cells are used to determine the anti-inflammation effect of 4',7-dihydroxyflavone.The results showed that 38 pharmacodynamic molecules of DB were predicted by the above methods,and 171 target proteins were obtained by direct or indirect predicable methods.Based on the target proteins,we analyzed their biological processes.Cluster analysis showed that 58 proteins were closely related to the occurrence and pathological process of ischemic stroke,and these 58 protein targets could be used to predict the pathobiology process of ischemic stroke.Through the CTD and TTD database analyzing,58 potential targets and 61 ischemic stroke related diseases are acquired after deleting repetition.At the pathway level,DB may play a role in treating ischemic stroke by resisting ischemia-induced cell death,enhancing cell survival,resisting microglial activation-mediated neuroinflammation,antiplatelet activation and blood pressure regulation.This study not only explained the underlying molecular mechanism of DB in the prognosis of ischemic stroke,but also illustrated loureirin B may protect PC12 cells from OGD/R damage by activating PI3K/AKT/CREB and Nrf2 pathway to increase the expression of HO-1 and Bcl-2.It also provided an important reference for future drug development based on DB and its extracts. |
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