ABSTRACT
Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Subject(s)
Mice , Rats , Animals , Myeloid Differentiation Factor 88/metabolism , Vascular Remodeling , Cell Proliferation , Vascular System Injuries/pathology , Carotid Artery Injuries/pathology , Molecular Docking Simulation , Muscle, Smooth, Vascular , Cell Movement , Mice, Inbred C57BL , Signal Transduction , Succinates/pharmacology , Potassium/pharmacology , Cells, Cultured , Diterpenes , CadherinsABSTRACT
<p><b>OBJECTIVE</b>To systematically evaluate the clinical efficacy and safety of Potassium Dehydroandrographolide Succinate Injection (PDSI) in the treatment of child epidemic parotitis (EP).</p><p><b>METHODS</b>Randomized controlled trials (RCTs) regarding PDSI in the treatment of child EP were searched in China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, PubMed, and Cochrane Library from inception to July 30, 2013. Two reviewers independently retrieved RCTs and extracted information. The Cochrane risk of bias method was used to assess the quality of included studies, and a meta-analysis was conducted with RevMan 5.2 software.</p><p><b>RESULTS</b>A total of 11 studies with 818 participants were included. The quality of the studies was generally low, among which only one study mentioned the random method. The meta-analysis indicated that PDSI was more effective than the conventional therapy with Western medicine for EP in the outcomes of the total effective rate [relative risk (RR)=1.23, 95% confidence interval (CI) [1.14, 1.33], P<0.01], the time of temperature return to normal, the time of detumescence [mean difference (MD)=-2.10, 95% CI [-2.78,-1.41], P<0.01], and the incidence of complications (RR=0.14, 95% CI [0.03, 0.72], P=0.02). There were 6 adverse drug reactions (ADRs) in this systematic review, 2 of which were mainly represented rash and diarrhea in the experiment group, while another 4 ADRs occurred in the control group.</p><p><b>CONCLUSIONS</b>Based on the systematic review, PDSI was effectiveness and relatively safety in the treatment of child EP. But further rigorously designed trials are warranted to determine its effectiveness.</p>
Subject(s)
Humans , Diterpenes , Mumps , Drug Therapy , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE:To prepare Potassium dehydroandrographolide succinate(PDS)hollow suppository and establish a method for its quality control.METHODS:The PDS hollow suppository was prepared with semisynthesis fatty acid glyceride as ground substances and PEG300 or 1,2 propylene glycol as disperse medium.The content of PDS was determined by ultraviolet spectrophotometry at a detection wavelength of 251nm.RESULTS:The linear concentration range of PDS was 6.0～50.0?g?mL-1(r=0.999 9,n=5).The two kinds of PDS hollow suppository were all up to the quality standard.CONCLUSION:This method is reasonable in design and feasible in technology.
ABSTRACT
OBJECTIVE:To study the effect of HP-?-CD on the stability of potassium dehydroandrographolide succina_ te solution.METHODS:The stability of the testing group(potassium dehydroandrographolide succinate solution+HP-?-CD)was determined by a thermostatic accelerated test with the content variation of potassium dehydroandrographolide succi?nate solution as an index and the potassium dehydroandrographolide succinate solution that was free of HP-?-CD as the control.RESULTS:The content variation of the testing group was less as against the control group,the terms of validity for the2groups were0.657y and3.40y respectively.CONCLUSION:The stability of potassium dehydroandrographolide succi?nate solution can be increased by adding HP-?-CD to which.
ABSTRACT
Objective To study the stability of potassium dehydroandrographolide succinate solution in different conditions.Methods The classical thermostatic test was adopted to investigate the stability of potassium dehydroandrographolide succinate in phosphate buffer solutions of different pH values,in different buffer solutions of the same pH value and in citrate buffer solutions of different concentrations.Results The stability of potassium dehydroandrographolide succinate solution was different at different pH values and was the best at pH 6.5.In various buffer solutions of pH 6.5,the hydrolyzation of potassium dehydroandrographolide succinate solution was delayed by citrate buffer solution,and the stability of the solution had no correlation with the concentration of citrate buffer solution.Conclusion The stability of potassium dehydroandrographolide succinate solution varies in different conditions.This will supply a reference for the study on potassium dehydroandrographolide succinate solution and its similar preparations.