Retinal vein occlusion (RVO) is a common clinical disease causing vision loss. Risk factors such as diabetes, atherosclerosis are closely associated with RVO. Xuesaitong injection is used extensively in clinical treatment of RVO, however the mechanism is still unclear. In this study, we investigated the protective effect of Xuesaitong injection on RVO rat model. Using a compound-target network of Xuesaitong on anti-RVO constructed by literature mining, we aim to elucidate the multi-compound, multi-target effect of Xuesaitong injection. Fifteen potential targets of Xuesaitong injection associated with inflammation, angiogenesis, apoptosis, and coagulation were identified in this study. VEGF, IL-1beta and IL-6, three important targets in the compound-target network were further experimentally validated. This study provided experimental evidence for Xuesaitong injection being effective in treating RVO and a network view on its anti-RVO mode of action through a multi-compound and multiple-target mechanism.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; Gene Regulatory Networks ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Retinal Vein Occlusion ; drug therapy ; genetics ; metabolism

AIMTo select higher thrombolytic and lower toxic single component of earthworm fibrinolytic enzymes (EFE).

METHODSEFE containing total components were obtained by affinity chromatography from Eisenia fetida. Using ion-exchange chromatography to separate three main components EfP-0-2, EfP-I-1 and EfP-I-2 from EFE, their thrombolytic activity and toxicity were compared with EFE.

RESULTSAmong these components, EfP-I-1 had higher thrombolytic activity in vitro. When 4.5 mg x kg(-1) of these components were injected, the contents of fibrinogen in rat serum were not affected, but only EfP-I-1 exhibited distinct thrombolytic activity. When 6.0 mg x kg(-1) of them were injected intravenously, the bleeding time was not evidently delayed only by EfP-I-1. The acute toxicity test showed that the LD50 of EfP-I-1 was higher than EFE by 2. 17 times.

CONCLUSIONBecause of distinct thrombolytic activity, lower toxicity in vivo, higher content in EFE and easy to purify, EfP-I-1 was adapted to be developed as a single component medicine for treating thrombus.

Amino Acid Sequence ; Animals ; Bleeding Time ; Dogs ; Electrophoresis, Polyacrylamide Gel ; Female ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; chemistry ; isolation & purification ; pharmacology ; toxicity ; Lethal Dose 50 ; Male ; Mice ; Molecular Sequence Data ; Molecular Weight ; Oligochaeta ; chemistry ; enzymology ; Rats ; Rats, Wistar ; Sequence Analysis, Protein ; Spectrophotometry, Infrared ; Venous Thrombosis ; blood ; drug therapy

AIMTo study the effects of rhBNP and milrinone on the cardiac hemodynamics and renal function in anesthetized dogs.

METHODSThe actions of rhBNP given cumulatively i.v. 10, 30 and 100 ng.kg-1 for 30 min and milrinone of single dose (100 micrograms.kg-1, i.v.) on cardiac hemodynamics and renal function were studied in anesthetized open-chest dogs.

RESULTSIn anesthetized dogs (n = 7) intravenous infusion of rhBNP at 10-100 ng.kg-1, caused decreases in mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), LVdp/dtmax, pulmonary arterial pressure (PAP), left ventricular end diastolic pressure (LVEDP), total peripheral resistance (TPR) and renal vascular resistance (RVR) dose-dependently, without significant changes in cardiac output (CO), LV(dp/dt)/P, renal blood flow (RBF) and heart rate (HR), increases in urinary volume and sodium excretion. In anesthetized dogs (n = 6), there were remarkable decreases in MAP, LVEDP, PAP, TPR, RBF, RVR and urinary volume following the MIL (100 micrograms.kg-1, i.v.), with significant increases of LVSP, +/- LVdp/dtmax, HR and CO, but no marked changes in urinary volume and sodium excretion.

CONCLUSIONrhBNP reduces the pre-load and after-load in the anaesthetized dogs but showed no distinct effect on the contractility of the heart. Positive inotropic and chronotropic actions have been demonstrated after intravenous injection of milrinone 100 micrograms.kg-1 in anesthetized dogs.

Anesthesia ; Animals ; Cardiotonic Agents ; pharmacology ; Dogs ; Drug Interactions ; Female ; Heart ; drug effects ; physiology ; Hemodynamics ; Kidney ; drug effects ; physiology ; Male ; Milrinone ; pharmacology ; Natriuretic Peptide, Brain ; pharmacology ; Recombinant Proteins ; pharmacology ; Sodium ; blood ; urine ; Urine

Objective To observe the effects of Batroxobin Injection on thromboembolic cerebral stroke by magnetic resonance imaging (MRI) and TTC staining.Methods Rat model ofthromboembolic stroke was prepared after the left middle cerebral artery was occluded by autologous blood clots,and 32 rats with successful operation were divided into four groups according to the degree of neurological deficit:model group,Batroxobin Injection low and high dose (0.3,1.0 BU/kg) group,and rt-PA (9 mg/kg) group,with eight rats in each group,and other eight rats in Sham group.Rats were administered 1 h after modeling by tail iv method.At 6 h after administration,neurological deficit score and MRIincluding SE-T2WI and DWI sequence scanning were measured.At 24 h after administration,the brain was cut for TTC staining to measure the infarct area,and blood FIB was measured.Results Compared with model group,Batroxobin Injection 0.3 BU/kg treatment for 24 h (P ＜ 0.05),1 BU/kg treatment for 6 and 24 h (P ＜ 0.05,0.01) could significntly improve the neurological function scores of rats.MRIresults showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the lesion range (P ＜ 0.05 and 0.01).Results of TTC stain showed that Batroxobin Injection at dose of 0.3 and 1 BU/kg significantly reduced the infarct size (P ＜ 0.05).Batroxobin Injection at doses of 0.3 and 1 BU/kg can significantly lower plasma FIB concentration (P ＜ 0.05,0.01,0.001) 6 and 24 h after administration.Conclusion Batroxobin Injection can improve the damaged neural function,reduce scope of lesions,decrease plasma fibrinogen,with protective effects for cerebral ischemia in rats.

Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3-demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM.
Anti-Bacterial Agents ; chemistry ; isolation & purification ; China ; Indoles ; chemistry ; isolation & purification ; Micromonosporaceae ; chemistry ; Structure-Activity Relationship

When this paper was first published the following ethical statement was omitted in error: This study was approved by the Ethics Committee of AAALAC (NO. 001488) and carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused. DOI of original article: https://doi.org/10.1016/j.chmed.2018.12.002

When this paper was first published the following ethical statement was omitted in error: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused.

Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3-demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM.