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 Effect of Compound Chuanxiong Capsule on Inflammatory Reaction and PI3K/Akt/NF-κB Signaling Pathway in Atherosclerosis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qunfu Kang ◽  
Weihong Liu ◽  
Hongxu Liu ◽  
Mingxue Zhou
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Reaction ◽  
High Fat Diet ◽  
Blood Lipids ◽  
High Dose ◽  
High Fat ◽  
Herbal Compound ◽  
Antiatherosclerotic Effect ◽  
Chinese Herbal Compound ◽  
Fat Feeding

Compound Chuanxiong Capsule (CCC), a Chinese herbal compound, can exhibit antiatherosclerotic effect; however, its mechanism is still unclear. This study is designed to study the mechanism of CCC on atherosclerosis in the ApoE-knockout (ApoE−/−) mice fed with a high-fat diet. After 6 weeks of high-fat feeding, 40 ApoE−/−mice were randomized (n=10) and treated with lipitor, high-dose or low-dose CCC, or distilled water (ApoE−/−group) for 7 weeks. The blood lipids in serum and the plaque areas of the mice were measured and the mRNA expressions of phosphatidylinositol-3-kinases (PI3K), Akt, nuclear factor-kappa B (NF-κB), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) of the aortae were determined. The data showed that CCC can significantly decrease the levels of blood lipids, atherosclerosis index, and plaque areas and increase collagen proportion in plaques as compared with the untreated mice (p<0.05,p<0.01). In addition, CCC can significantly reduce the mRNA expressions of PI3K, Akt, NF-κB, IL-6, and TNF-αin the mice fed with a high-fat diet (p<0.001). Thus, we concluded that CCC can inhibit inflammatory reaction in the ApoE−/−mice fed with a high-fat diet. This mechanism may be attributed to regulating PI3K/Akt/NF-κB signaling pathway.

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 Deoxynivalenol Induces Intestinal Damage and Inflammatory Response through the Nuclear Factor-κB Signaling Pathway in Piglets

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 663 ◽  
Author(s):  
Xi-Chun Wang ◽  
Ya-Fei Zhang ◽  
Li Cao ◽  
Lei Zhu ◽  
Ying-Ying Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Basal Diet ◽  
Nuclear Factor Κb ◽  
Control Group ◽  
High Dose ◽  
Intestinal Damage ◽  
Small Intestinal Mucosa ◽  
Mrna Levels ◽  
Nuclear Factor

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 μg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/β, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.

scholarly journals Salidroside Modulates Insulin Signaling in a Rat Model of Nonalcoholic Steatohepatitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hongshan Li ◽  
Hao Ying ◽  
Airong Hu ◽  
Dezhou Li ◽  
Yaoren Hu
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Insulin Signaling ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Insulin Signaling Pathway ◽  
Hepatic Tissue ◽  
Therapeutic Effects ◽  
High Fat

A growing body of evidence has shown the beneficial effects of salidroside in cardiovascular and metabolic diseases. This study aimed to evaluate the therapeutic effects of salidroside on nonalcoholic steatohepatitis (NASH) in rats and explore the underlying mechanisms related to insulin signaling. A rat model of NASH was developed by high-fat diet for 14 weeks. From week 9 onward, the treatment group received oral salidroside (4.33 mg/kg) daily for 6 weeks. Salidroside effectively attenuated steatosis and vacuolation of hepatic tissue, with a dramatic decrease in liver triglycerides and free fatty acid levels (P < 0.01). Dysregulation of FINS, FBG, HOMA-IR, ALT, and AST in serum was ameliorated with salidroside treatment (P < 0.01). In the liver, salidroside induced significant increases in key molecules in the insulin signaling pathway, such as phosphorylated insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB), with a significant decrease in SREBP-1c levels (P < 0.01). Therefore, salidroside effectively protected rats from high-fat-diet-induced NASH, which may be partially attributed to its effects on the hepatic insulin signaling pathway.

scholarly journals Effects of Thalidomide on the Expression of Adhesion Molecules in Rat Liver Cirrhosis

2006 ◽  
Vol 2006 ◽  
pp. 1-10 ◽  
Author(s):  
Peng Lv ◽  
Shelley Chireyath Paul ◽  
Yanjv Xiao ◽  
Shiquan Liu ◽  
Hesheng Luo
Keyword(s):  
Liver Cirrhosis ◽  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Adhesion Molecules ◽  
Rat Liver ◽  
Intraperitoneal Injection ◽  
Wistar Rats ◽  
High Dose ◽  
Intragastric Administration ◽  
Liver Histopathology

This study was to evaluate the effects of thalidomide on expression of adhesion molecules in liver cirrhosis. The cirrhosis was induced in Wistar rats by intraperitoneal injection ofCCl4, and thalidomide (10 mg/kg/day or 100 mg/kg/day) was given by intragastric administration for 8 weeks. Liver histopathology and immunohistochemistry were significantly improved and the expressions of ICAM-1, VCAM-1, E-selectin, and TNF-αmRNA and protein were decreased significantly in rats treated with a high dose of thalidomide. Close positive correlation was observed in the expression of the TNF-αmRNA and that of ICAM-1, VCAM-1, and E-selectin mRNA, respectively. These results indicate that thalidomide exerts its effect on the downregulation of adhesion molecules via TNF-αsignaling pathway to inhibit liver fibrosis.

scholarly journals Icariin Restores Bone Structure and Strength in a Rat Model of Chronic High-Dose Alcohol-Induced Osteopenia

2018 ◽  
Vol 46 (4) ◽  
pp. 1727-1736 ◽  
Author(s):  
Jie-Zhou Wu ◽  
Peng-Cheng Liu ◽  
Run Liu ◽  
Ming Cai
Keyword(s):  
Mechanism Of Action ◽  
Rat Model ◽  
Low Dose ◽  
Bone Structure ◽  
Biomechanical Properties ◽  
High Dose ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Alcohol Group

Background/Aims: Chronic alcohol abuse is an important risk factor for osteopenia. However, few studies have focused on the efficacy and mechanism of action of icariin on alcohol-induced osteopenia. The aim of this study was to investigate the efficacy and underlying mechanism of action of icariin in the treatment of chronic high-dose alcohol-induced osteopenia in a rat model. Methods: Thirty-six adult male Sprague-Dawley rats were randomly divided into four groups: sham, alcohol, and low-dose and high-dose icariin groups. Bone volume fraction (BV/TV), bone mineral density (BMD), bone biomechanical properties, and bone morphology were assessed after 16 weeks. Reverse-transcription PCR was used to detect mRNA expression levels of alkaline phosphatase (ALP), collagen type I (Col I), osteocalcin (OC), runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteoprotegerin (OPG). Results: Bone metabolic markers and biomechanical properties in the alcohol group were decreased significantly compared with the sham group. BV/TV, BMD, mineral apposition rate (MAR), percent trabecular area (%Tb.Ar), and bone biomechanical properties were elevated in the low-dose and high-dose icariin groups relative to the alcohol group. ALP, Col I, OC, Runx2, BMP-2, and OPG mRNA levels in the icariin group were significantly elevated in comparison with the alcohol group. Conclusion: Icariin can prevent overall progression of chronic high-dose alcohol-induced osteopenia in a rat model, in a dose-dependent manner. Icariin promotes bone formation and inhibits bone loss, and effectively restores bone structure and strength in chronic high-dose alcohol-induced osteopenic rats. Bone metabolism reversal is evidenced by increased BV/TV, BMD, MAR, %Tb.Ar, and biomechanical properties and elevated ALP, Col I, OC, Runx2, BMP-2, and OPG mRNA levels.

scholarly journals Rosuvastatin exerts favourable effects on thrombosis and neointimal growth in a mouse model of endothelial injury

2005 ◽  
Vol 93 (01) ◽  
pp. 145-152 ◽  
Author(s):  
Katrin Schäfer ◽  
Kilian Kaiser ◽  
Stavros Konstantinides
Keyword(s):  
Arterial Thrombosis ◽  
Plasma Lipid ◽  
Statin Treatment ◽  
Endothelial Injury ◽  
Vascular Lesions ◽  
Lipid Lowering ◽  
High Dose ◽  
Lipid Levels ◽  
Antithrombotic Effects ◽  
Coa Reductase

SummaryApart from reducing systemic lipid levels, statins may improve the clinical course of atherosclerosis by exerting favourable pleiotropic effects on the vessel wall.We studied the effects of rosuvastatin, a new, potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on vascular remodelling after endothelial injury in the hyperlipidaemic apolipoprotein E-knockout (apoE-/-) mouse. ApoE-/- mice, 22-weeks-old, were injected daily with rosuvastatin at a low (1 mg/kg; n=27) or high dosage (10 mg/kg; n=24), or with vehicle alone (n=26).After treatment for 2 weeks,endothelial injury and thrombosis of the carotid artery was induced with 10% ferric chloride.Treatment was then resumed for a 3-week period.Although statin treatment did not affect the plasma lipid levels of mice, mean times to arterial thrombosis were prolonged in the low-dose and the high-dose group compared to controls (P<0.05 and P<0.01 respectively). Interestingly, rosuvastatin withdrawal 4 days before injury completely reversed the antithrombotic effects of the drug. In follow-up studies 3 weeks after injury,deposition of fibrin in the vessel wall was significantly reduced in the rosuvastatin-treated animals. There was an increase in the content of α -actin-positive smooth muscle cells (P =0.008) and collagen fibers (P<0.001), and a concomitant decrease in the number of oxLDL-containing macrophages (P<0.001). Overall, the neointimal area and the severity of luminal stenosis were significantly reduced in statin-treated mice. Thus, rosuvastatin attenuates arterial thrombosis and neointima formation, and it may stabilise vascular lesions developing after endothelial injury in mice.These effects are independent of systemic lipid lowering.

scholarly journals High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ai-Ping Pang ◽  
Haiyan Wang ◽  
Funing Zhang ◽  
Xin Hu ◽  
Fu-Gen Wu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cellulase Production ◽  
High Dose ◽  
Mrna Levels ◽  
Tor Signaling ◽  
Inhibition Effect ◽  
Temporary Inhibition ◽  
Rut C30

Abstract Background Knowledge with respect to regulatory systems for cellulase production is prerequisite for exploitation of such regulatory networks to increase cellulase production, improve fermentation efficiency and reduce the relevant production cost. The target of rapamycin (TOR) signaling pathway is considered as a central signaling hub coordinating eukaryotic cell growth and metabolism with environmental inputs. However, how and to what extent the TOR signaling pathway and rapamycin are involved in cellulase production remain elusive. Result At the early fermentation stage, high-dose rapamycin (100 μM) caused a temporary inhibition effect on cellulase production, cell growth and sporulation of Trichoderma reesei RUT-C30 independently of the carbon sources, and specifically caused a tentative morphology defect in RUT-C30 grown on cellulose. On the contrary, the lipid content of T. reesei RUT-C30 was not affected by rapamycin. Accordingly, the transcriptional levels of genes involved in the cellulase production were downregulated notably with the addition of rapamycin. Although the mRNA levels of the putative rapamycin receptor trFKBP12 was upregulated significantly by rapamycin, gene trTOR (the downstream effector of the rapamycin–FKBP12 complex) and genes associated with the TOR signaling pathways were not changed markedly. With the deletion of gene trFKBP12, there is no impact of rapamycin on cellulase production, indicating that trFKBP12 mediates the observed temporary inhibition effect of rapamycin. Conclusion Our study shows for the first time that only high-concentration rapamycin induced a transient impact on T. reesei RUT-C30 at its early cultivation stage, demonstrating T. reesei RUT-C30 is highly resistant to rapamycin, probably due to that trTOR and its related signaling pathways were not that sensitive to rapamycin. This temporary influence of rapamycin was facilitated by gene trFKBP12. These findings add to our knowledge on the roles of rapamycin and the TOR signaling pathways play in T. reesei.

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.

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