scholarly journals Protective Effects of Total Flavones ofElaeagnus rhamnoides(L.) A. Nelson against Vascular Endothelial Injury in Blood Stasis Model Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Zhicheng Wei ◽  
Fang Zuo ◽  
Wenqian Wang ◽  
Li Wang ◽  
Dong Tong ◽  
...  
Keyword(s):  
Rat Model ◽  
Caspase 3 ◽  
Blood Stasis ◽  
Endothelial Injury ◽  
Water Bath ◽  
High Dose ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Von Willebrand ◽  
Ice Water

The aim was to evaluate the protective effects of total flavones ofElaeagnus rhamnoides(L.) A. Nelson (TFE) against vascular endothelial injury in blood stasis model rats and explore the potential mechanisms preliminarily. The model of blood stasis rat model with vascular endothelial injury was induced by subcutaneous injection of adrenaline combined with ice-water bath. Whole blood viscosity (WBV), histological examination, and prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were measured. Meanwhile, the levels of Thromboxane B2 (TXB2), 6-keto-PGF1α, von Willebrand factor (vWF), and thrombomodulin (TM) were detected. In addition, Quantitative Real-Time PCR (qPCR) was performed to identify PI3K, Erk2, Bcl-2, and caspase-3 gene expression. The results showed that TFE can relieve WBV, increase PT and APTT, and decrease FIB content obviously. Moreover, TFE might significantly downregulate the levels of TXB2, vWF, and TM in plasma and upregulate the level of 6-keto-PGF1αin plasma. Expressions of PI3K and Bcl-2 were increased and the expression of caspase-3 was decreased by TFE pretreatment in the rat model. Consequently, the study suggested that TFE may have the potential against vascular endothelial injury in blood stasis model rats induced by a high dose of adrenaline with ice-water bath.

scholarly journals Experimental Study on the Effect of Aconite and Angelica sinensis on Myocardial Ischemia Rats with Yang Deficiency and Blood Stasis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yongcang Cao ◽  
Xiaodong Liang ◽  
Changyi Li ◽  
Tao Chen ◽  
Zhanling Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Rat Model ◽  
Caspase 3 ◽  
Blood Stasis ◽  
Angelica Sinensis ◽  
Control Group ◽  
High Dose ◽  
Group Model ◽  
Rat Cardiomyocytes ◽  
Bax Protein

Objective. To investigate the intervention effect and mechanism of Aconite and Angelica sinensis on myocardial ischemia rats with Yang deficiency and blood stasis. Methods. SPF-class SD rats were randomly divided into low-dose and high-dose groups. Each group was divided into control group, model group, and drug-administered group (FZ, DG, FG; 1 : 0.5, 1 : 1, 1 : 2). A rat model was prepared by intraperitoneal injection of hydrocortisone and isoproterenol plus cold stimulation. Each group was given corresponding decoction or distilled water for 14 days. The behavioral changes of rats in each group were observed. The morphological changes of rats cardiomyocytes were observed by HE staining. The average optical density (MOD value) and percentage of positive cells of Bcl-2, Bax, and Akt were determined by immunohistochemical staining method, and PEIs were calculated. Western blot and RT-PCR were used to determine the expression of PI3K, Caspase-3, Akt protein, and gene expression. Results. The compatibility of Aconite and Angelica sinensis improved the morphology of rat cardiomyocytes, increased the PEI values of Akt and Bcl-2 protein, and decreased the PEI values of Bax protein (P<0.01). The compatibility reduced the expression of Caspase-3 protein of rat myocardium and increased the protein expression of p-Akt, PI3K, and p-PI3K (P<0.01). The compatibility also significantly reduced the expression of Caspase-3 mRNA and increased the expression of PI3K mRNA and Akt mRNA (P<0.05 or P<0.01), and the effect of high-dose FG (1 : 2) group is the best. Conclusions. The method of preparing a rat model of myocardial ischemia with Yang deficiency and blood stasis was feasible. The compatibility of Aconite and Angelica sinensis reduced myocardial fibrosis and inflammatory reaction, protected ischemic cardiomyocytes, and reduced myocardial injury, whose mechanism may be related to the regulation of PI3K/Akt pathway. The compatible group had better intervention effects than Aconite or Angelica sinensis alone. The best one was high-dose FG (1 : 2).

scholarly journals Activation of caspase-3 may not contribute to postresuscitation myocardial dysfunction

2009 ◽  
Vol 296 (4) ◽  
pp. H1164-H1174 ◽  
Author(s):  
Jeejabai Radhakrishnan ◽  
Iyad M. Ayoub ◽  
Raúl J. Gazmuri
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Rat Model ◽  
Caspase 3 ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Stroke Work ◽  
Protective Effects ◽  
Apoptotic Pathway ◽  
Apoptosis Protein

We have previously reported that postresuscitation myocardial dysfunction is accompanied by the release of cytochrome c and caspase-3 activation. We now investigated the role of caspase-3 activation by examining whether such process prompts apoptotic DNA fragmentation, whether caspase-3 inhibition attenuates myocardial dysfunction, and whether myocardial protective effects of sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition involve caspase-3 inhibition using a rat model of ventricular fibrillation (VF) of closed-chest resuscitation. Resuscitation after 4 or 8 min of untreated VF caused significant reductions in left ventricular stroke work index averaging 23% of sham control rats at 4 h postresuscitation. Left ventricular dysfunction was accompanied by increases in cytosolic cytochrome c, decreases in pro- and cleaved caspase-9 fragments, increases in 17-kDa caspase-3 fragments, and increases in caspase-3 activity indicating the activation of the mitochondrial apoptotic pathway but without evidence of apoptotic DNA fragmentation. In addition, levels of heat shock protein 70 were increased and levels of X-linked inhibitor of apoptosis protein and αβ-crystallin were preserved, all of which can exert antiapoptotic effects. In a separate series, the caspase-3 inhibitor z-Asp-Glu-Val-Asp chloromethyl ketone given before the induction of VF failed to prevent postresuscitation myocardial dysfunction despite reductions in caspase-3 activity (2.3 ± 0.5 vs. 1.3 ± 0.5 pmol fluorophore AFC released·mg protein−1·min−1; P < 0.03). Treatment with the NHE-1 inhibitor cariporide had no effect on caspase-3 activity. Accordingly, in this rat model of VF and severe postresuscitation myocardial dysfunction, activation of caspase-3 did not lead to DNA fragmentation or contribute to myocardial dysfunction. Concomitant activation of intrinsic antiapoptotic mechanisms could play a protective role downstream to caspase-3 activation.

scholarly journals Regulation of Bcl-2 and the NF-kB Signaling Pathway by Succinyl Rotundic Acid in Livers of Rats with Alcoholic Hepatitis

2021 ◽  
Vol 25 (03) ◽  
pp. 730-734
Author(s):  
Yufang He
Keyword(s):  
Alcoholic Hepatitis ◽  
Caspase 3 ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Signal Pathways ◽  
High Dose ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Protein Levels ◽  
Rotundic Acid

In this study, the protective effects of succinyl rotundic acids on alcoholic hepatitis in irradiated rats as well as the effects of Bcl-2-Bax-caspase-3 and the NF-kB signal pathways were studied. SD rats were divided into four groups randomly: normal; model; and succinyl rotundic acid low-, middle-, and high-dose groups. Distilled water, 60% ethanol and 60% ethanol +SRA, respectively, were given for 30 days. ELISA was used to measure serum levels of LDH, AST, ALT, NOS, NO, MDA, GSH and TG. Western blotting was used to measure protein levels of Bcl-2, Bax, caspase-3, NF-kB p 65, IKBA, HO-1, Nrf2 and CYP2E1. Compared with the model group, LDH, AST, ALT, NOS, NO, MDA and TG levels were lower in serum of low-, middle-, and high-dose groups (P < 0.01, P < 0.05 and P < 0.05 in all); GSH content was greater in serum of low-, middle- and high-dose groups (P < 0.05). Levels of Bcl-2, HO-1, and Nrf2 were greater (P < 0.01 in all); those of Bax, caspase-3, NF-kB p65, IKBA, and CYP2E1 were lower (P < 0.01 and P < 0.001 in all). These findings suggest that succinyl rotundic acid reduces inflammatory reactions by reducing levels of NOS and NO, regulating levels of Bcl-2, Bax, caspase-3, NF-kB, and anti-oxidative stress pathways, and has an antagonistic effect on alcoholic liver injury. The agent has potential to treat clinical alcoholic liver disease. © 2021 Friends Science Publishers

Protective Effects of Allicin on ISO-Induced Rat Model of Myocardial Infarction via JNK Signaling Pathway

Pharmacology ◽  
2020 ◽  
Vol 105 (9-10) ◽  
pp. 505-513
Author(s):  
Wen Xu ◽  
Xiang-peng Li ◽  
En-ze Li ◽  
Yue-fen Liu ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathway ◽  
Rat Model ◽  
Dose Group ◽  
Sham Group ◽  
High Dose ◽  
Protective Effects ◽  
Jnk Signaling ◽  
T Wave ◽  
Jnk Signaling Pathway

<b><i>Objective:</i></b> This research was aimed to explore protective effects of allicin on rat model of myocardial infarction via JNK signaling pathway. <b><i>Methods:</i></b> Rat myocardial ischemia model was established with subcutaneous injection of isoproterenol (ISO). Seventy-five rats were randomly divided into 5 groups (<i>n</i> = 15): sham group, ISO group, low-dose group (1.2 mg/kg/days for 7 days), medium-dose group (1.8 mg/kg/days for 7 days), and high-dose group (3.6 mg/kg/days for 7 days). Routine HE staining and Masson staining were performed to observe myocardial histopathology. The expression of oxidative stress-related indicators, heart tissue apoptosis-related proteins, and JNK and p-JNK proteins were measured for different groups. <b><i>Results:</i></b> Compared with the sham group, the T wave value of the ISO group was significantly increased (<i>p &#x3c;</i> 0.01). When allicin was administered, the T wave values at different time points in all groups were all decreased. Compared with the sham group, the ratio of eNOS, Bcl-2/Bax was significantly decreased, and p-eNOS, iNOS, caspase-3, caspase-9, and Cyt-c were significantly elevated in the ISO group (<i>p &#x3c;</i> 0.05). After allicin was administered, significant changes in these proteins were observed in the medium- and high-dose groups. There was no significant change in the expression of JNK protein in the ISO group compared with the sham group; however, the expression of eNOS and p-JNK protein were significantly upregulated (<i>p &#x3c;</i> 0.01) and the expression of p-eNOS and iNOS were significantly downregulated (<i>p &#x3c;</i> 0.01). When allicin was administered, expression of p-JNK protein was significantly downregulated. <b><i>Conclusion:</i></b> Allicin can reduce oxidative stress damage and cardiomyocyte apoptosis in rat model of myocardial infarction and can significantly regulate JNK signaling pathway.

scholarly journals α -Lipoic Acid-Plus Ameliorates Endothelial Injury via Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in Vivo and Vitro Endothelial Injury Model

2021 ◽  
Author(s):  
Yang Wang ◽  
Xiangqian Kong ◽  
Dejun Bao ◽  
Bin xu ◽  
Yongfei Dong ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Caspase 3 ◽  
Endothelial Injury ◽  
Protective Effects ◽  
Apoptosis Pathway ◽  
Protein Levels ◽  
Oxidative Stress Level ◽  
Intimal Injury

Abstract PurposeWe tried to explore the potential role of the α-Lipoic acid-plus (LAP) in endothelial injury in vitro and vivo models. Simultaneously, possible endovascular protective mechanisms of LAP were also investigated further. MethodsIn vitro, oxyhemoglobin (OxyHb) stimulating human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, carotid artery angioplasty injury was used to generate a model of rat carotid artery intimal injury (CAII). HUVECs and rats were treated with desferrioxamine (DFO) and LAP. ResultsIn experiment 1, we found that the expressions of Cathepsin B/D in endothelial tissue increased and reached peak point in 48 hours post rat CAII. In experiment 2, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin, Transferrin Receptor (TfR) markedly increased after CAII and reversed by DFO and LAP treatments. Besides, DFO and LAP treatments also reduced oxidative stress level and endothelial cells (ECs) necrosis of the damaged endometrium. In experiment 3, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin and TfR apparently increased post OxyHb stimulation, which were further aggravated by the addition of iron and decreased by DFO and LAP treatments. Moreover, DFO and LAP significantly ameliorated oxidative stress level, HUVECs injury, iron level, mitochondrial damage and were beneficial to maintain lysosomal integrity. Finally, LAP may have exerted more significant endovascular protective effects than DFO.ConclusionsLAP probably exerted endovascular protective effects via inhibiting the apoptosis pathway mediated by intralysosomal Cathepsins by chelating excessive iron in endothelial lysosomes post intimal injury.

scholarly journals Therapeutic Effect and Mechanism Study of Rhodiola wallichiana var. cholaensis Injection to Acute Blood Stasis Using Metabolomics Based on UPLC-Q/TOF-MS

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Nan Ran ◽  
Zhiqiang Pang ◽  
Xuewa Guan ◽  
Guoqiang Wang ◽  
Jinping Liu ◽  
...  
Keyword(s):  
Rat Model ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Blood Stasis ◽  
Blood Stasis Syndrome ◽  
Inflammatory Factors ◽  
Control Group ◽  
High Dose ◽  
Alpha Linolenic Acid ◽  
Model Control

In traditional Chinese medicine theory, blood stasis syndrome (BSS), characterized by blood flow retardation and blood stagnation, is one of the main pathologic mechanisms and clinical syndromes of cardiovascular diseases (CVDs). Rhodiola wallichiana var. cholaensis injection (RWCI) is made from dry roots and stems of RWC via the processes of decoction, alcohol precipitation, filtration, and dilution. Studies indicated the extracts of RWC could alleviate CVDs; however, the mechanism had not been illustrated. In the present study, the acute blood stasis rat model was established to investigate the pathogenesis of BSS and the therapeutic mechanism of RWCI against BSS. Hemorheological parameters (whole blood viscosity and plasma viscosity) and inflammatory factors (TNF-α and IL-6) were used to evaluate the success of the BSS rat model and RWCI efficacy. 14 and 33 differential metabolites were identified from plasma and urine samples using the metabolomics approach based on ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The results of multivariate analysis displayed that there were significant separations among model, control, and treatment groups, but the high-dose RWCI treatment group was closer to the control group. 9 perturbed metabolic pathways were related to BSS’s development and RWCI intervention. 5 metabolic pathways (arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, retinol metabolism, and steroid hormone biosynthesis) showed apparent correlations. These differential metabolites and perturbed metabolic pathways might provide a novel view to understand the pathogenesis of BSS and the pharmacological mechanism of RWCI.

scholarly journals Effect of Kangshuanyihao Formula on the Inflammatory Reaction and SIRT1/TLR4/NF-κB Signaling Pathway in Endothelial Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Han ◽  
Hua-Qin Tong ◽  
Song-Yi Cheng ◽  
Li Yang ◽  
Han-Yu Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Reaction ◽  
Rat Model ◽  
Intraperitoneal Injection ◽  
Endothelial Injury ◽  
High Dose ◽  
Mrna Levels ◽  
Lipid Levels ◽  
High Fat ◽  
Therapeutic Principles

Endothelial injury plays an important role in atherosclerosis (AS). Kangshuanyihao formula uses therapeutic principles from Chinese medicine to supplement Qi, thereby promoting blood circulation, and remove blood stasis. The mechanism by which the formula inhibits endothelial injury was examined in a rat model of 1,25-dihydroxyvitamin D3 (VD3) intraperitoneal injection and high-fat-induced endothelial injury. Rats were randomly divided into the model, high-dose, middle-dose, low-dose, positive drug (rosuvastatin), and combination (positive drug + middle-dose) groups; 10 Sprague-Dawley rats served as the blank group. The aortic endothelium was stained with hematoxylin and eosin and the levels of blood lipids and inflammation markers (mRNA and protein) were measured. Endothelial injury, lipid levels, and inflammation were increased in the model. Kangshuanyihao formula reduced endothelial injury, improved lipid levels, and downregulated inflammation, as shown by significant reduction of the protein levels of SIRT1, TLR4, and NF-κB and mRNA levels of SIRT1, TLR4, NF-κB, IL-1β, IL-6, and IL-12. Thus, we conclude that Kangshuanyihao formula can inhibit the inflammatory reaction in the rat model of high-fat-induced endothelial injury after intraperitoneal injection of VD3. This mechanism may be attributed to regulating the SIRT1/TLR4/NF-κB signaling pathway.

scholarly journals Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway

2021 ◽  
Author(s):  
Shi-ya Wang ◽  
Cao Zou ◽  
Xiao-feng Liu ◽  
Yon-jin Yan ◽  
Shun-zhon Gu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Caspase 3 ◽  
Saturated Fatty Acids ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Apoptosis Rate ◽  
Dependent Relation ◽  
Endothelial Growth Factor

AbstractEnhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

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