Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Study on acute kidney injury model induced by renal ischemia-reperfusion in rats / 中国中药杂志

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 μmol·L-1 to more than 430 μmol·L-1. Among them,5 rats showed less than 100 μmol·L-1 serum Crea,20 rats with 100-200 μmol·L-1 serum Crea and 12 rats with more than 430 μmol·L-1. Rats with serum Crea between 300-430 μmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 μmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 μmol·L-1 and the group of Crea 300-370 μmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 μmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.

Effect and Safety of Guanxinning Tablet () for Stable Angina Pectoris Patients with Xin (Heart)-Blood Stagnation Syndrome: A Randomized, Multicenter, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and safety of Guanxinning Tablet (, GXN) for the treatment of stable angina pectoris patients with Xin (Heart)-blood stagnation syndrome (XBSS).@*METHODS@#One hundred and sixty stable angina pectoris patients with XBSS were randomly assigned to receive GXN (80 cases) or placebo (80 cases, Guanxinning simulation tablets, mainly composed of lactose), 4 tablets (0.38 g/tablet), thrice daily for 12 weeks. After treatment, an exercise stress test (treadmill protocol), Chinese medicine (CM) syndrome score, electrocardiogram (ECG), and nitroglycerin withdrawal rate were evaluated and compared in the patients between the two groups. Meanwhile, adverse events (AEs) were evaluated during the whole clinical trial.@*RESULTS@#Compared with the control group, the time extension of exercise duration in the GXN group increased 29.28 ±17.67 s after treatment (P>0.05); moreover, the change of exercise duration in the GXN group increased 63.10 ±96.96 s in subgroup analysis (P<0.05). The effective rates of angina pectoris, CM syndrome and ECG as well as nitroglycerin withdrawal rate were 81.33%, 90.67%, 45.76%, and 70.73%, respectively in the GXN group, which were all significantly higher than those in the control group (40.58%, 75.36%, 26.92%, 28.21%, respectively, P<0.05).@*CONCLUSION@#GXN was a safe and effective treatment for stable angina pectoris patients with XBSS at a dose of 4 tablets, thrice daily.