Screening Safflower Injection for Constituents with Activity against Stroke Using Comprehensive Chemical Profiling Coupled with Network Pharmacology

Objective:This study aimed to explore safflower injection(SI)for constituents with activity against ischemic stroke using a combination of chemical analysis and a network pharmacology strategy.Materials and Methods:The main ingredients of SI were comprehensively identified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry,and the core targets and pathways associated with stroke were predicted using PharmMapper and Kyoto Encyclopedia of Genes and Genomes analysis.Cytoscape software was used to visualize and analyze the active compound-target-pathway network of SI regulating ischemic stroke.Results:A total of76 chemical compounds were identified from the SI sample,including 63,which regulated 88 targets that were ultimately enriched in 12 key ischemia stroke-related signaling pathways.Kaempferol-3-O-sophoroside,kaempferol-3-O-rutinoside,carthamoside B6,neoeriocitrin,and6-hydroxykaempferol-3-O-rutinoside-6-O-glucoside were determined to be important for stroke treatment because they had a higher degree value in the network than other constituents did.Moreover,the characteristic components isolated from SI showed protective effect mainly by acting on multiple targets including AKT1,epidermal growth factor receptor,transforming growth factor-beta receptor(TGFBR),Ras homolog,mTORC1 binding,caspase 3,and glycogen synthase kinase 3 beta,which were involved in different signaling pathways including phosphoinositide 3-kinase-Akt,mitogen-activated protein kinase,neurotrophin,ErbB,mechanistic target of rapamycin,and tumor necrosis factor.Conclusions:This study proposed a network pharmacology and chemical component profiling strategy for the systematic understanding of the therapeutic material basis of using SI against ischemic stroke.

A Clinical Study of Safflower Yellow Injection in Treating Coronary Heart Disease Angina Pectoris with Xin-Blood Stagnation Syndrome

Objective： To evaluate the clinical effect and safety of Safflower Yellow injection （SYI） in treating coronary heart disease angina pectoris （OHD-AP） with Xin-blood stagnation syndrome （XBSS）. Methods： Adopted was the multi-centered, randomized, positive parallel controlled method, 448 patients with CHD-AP-XBSS were enrolled and divided into two groups, 336 in the tested group treated with SYI and 112 in the control group treated with Salvia injection by intravenous dripping once a day for 14 days, so as to observe the conditions of angina, electrocardiogram, and therapeutic effect on traditinal Chinese medicine （TCM） symptoms as well as the safety of the treatment. Results： The significantly effective rate and total effective rate in the tested group were 60.06% （194/323） and 91.02 % （294/323） respectively; those in improvement of TOM symptoms were 40. 18% （129/321） and 75.23% （243/323） respectively, which were better than those in the control group （P〈0.01）. Conclusion： SYI Injection is effective and safe in treating OHD-AP-XBSS.

Safflower Extract and Aceglutamide Injection Promoting Recovery of Peripheral Innervations via Vascular Endothelial Growth Factor-B Signaling in Diabetic Mice

Background： Safflower extract and aceglutamide （SA） has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage, and mental deterioration. This study aimed to investigate the effect and mechanism of SA injection in the recovery of peripheral innervations of diabetic mice. Methods： The C57BL/6 male mice were divided into four groups： normal control group （n = 44）, diabetic group （n = 44）, diabetic ＋ SA group （diabetic mice treated with SA injection, n = 44）, and diabetic ＋ SA ＋ vascular endothelial growth factor receptor （VEGFR）1-BL group （diabetic mice treated with SA injection and VEGFR 1 blocking antibody n = 24）. The streptozotocin-induced diabetic mice model and injured peripheral nerve mice model were built. The mice with injured peripheral nerves were intraperitonealy administered with SA injection for successive 21 days. The corneal sensitivity, number of corneal nerve fibers, and contents of vascular endothelial growth factor （VEGF）-B and various neurotrophic factors such as nerve growth factor （NGF） and glial cell line-derived neurotrophic factor （GDNF） in corneal tissue of four groups were observed. Results： The diabetic group showed decreased number of corneal nerve fibers, compared with the control group （P = 0.002）. And compared with the diabetic group, the diabetic ＋ SA group showed a significant increase in the number of nerve fibers （P = 0.024） and the contents of VEGF-B,NGF,andGDNFinthecornea（allP〈0.05）.However,whenthediabeticmiceweretreatedwiththeblockingantibodiesspecializedfor VEGF-B receptor, the neutralization ofVEGFR-1 completely abolished the increased expression of NGF and GDNF stimulated by SAinjection. Conclusions： SA injection could reduce the nerve injury caused by diabetic peripheral neuropathy, and its protective effect might be associated with the promotion of the expressions of VEGF-B, NGF, and GDNF.