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 Chlorogenic Acid Attenuates Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice through MAPK/ERK/JNK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Wenyan Gao ◽  
Changhong Wang ◽  
Li Yu ◽  
Tianjiao Sheng ◽  
Zhuolin Wu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Protective Effect ◽  
Chlorogenic Acid ◽  
Signaling Pathway ◽  
Dose Group ◽  
Damage Index ◽  
Control Group ◽  
High Dose ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Objective. Observe the protective effect of chlorogenic acid on dextran sulfate-induced ulcerative colitis in mice and explore the regulation of MAPK/ERK/JNK signaling pathway. Methods. Seventy C57BL/6 mice (half males and half females) were randomly divided into 7 groups, 10 in each group: control group (CON group), UC model group (UC group), and sulfasalazine-positive control group (SASP group), chlorogenic acid low dose group (CGA-L group), chlorogenic acid medium dose group (CGA-M group), chlorogenic acid high dose group (CGA-H group), and ERK inhibitor + chlorogenic acid group (E+CGA group). The effects of chlorogenic acid on UC were evaluated by colon mucosa damage index (CMDI), HE staining, immunohistochemistry, ELISA, and Western blot. The relationship between chlorogenic acid and MAPK/ERK/JNK signaling pathway was explored by adding ERK inhibitor. Results. The UC models were established successfully by drinking DSS water. Chlorogenic acid reduces DSS-induced colonic mucosal damage, inhibits DSS-induced inflammation, oxidative stress, and apoptosis in colon, and reduces ERK1/2, p -ERK, p38, p-p38, JNK, and p-JNK protein expression. ERK inhibitor U0126 reversed the protective effect of chlorogenic acid on colon tissue. Conclusion. Chlorogenic acid can alleviate DSS-induced ulcerative colitis in mice, which can significantly reduce tissue inflammation and apoptosis, and its mechanism is related to the MAPK/ERK/JNK signaling pathway.

scholarly journals Resveratrol improves cardiac function and left ventricular fibrosis after myocardial infarction in rats by inhibiting NLRP3 inflammasome activity and the TGF-β1/SMAD2 signaling pathway

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11501
Author(s):  
Jinjin Jiang ◽  
Xiuping Gu ◽  
Huifeng Wang ◽  
Shibin Ding
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Sham Operation ◽  
Protective Effects ◽  
Inflammasome Activity

Background Several studies have shown that resveratrol (RES), a naturally occurring polyphenol found in many plants, is beneficial for preventing cardiovascular diseases. However, the mechanism underlying the RES-mediated protection against myocardial infarction has not yet been revealed entirely. In this study, we investigated the protective effects of RES on cardiac function in a rat model of acute myocardial infarction (AMI) and the related underlying mechanisms. Methods Male Sprague-Dawley rats were randomly divided into four groups: Sham (sham operation), Sham-RES, AMI (AMI induction), and AMI-RES. The rat AMI model was established by the permanent ligation of left anterior descending coronary artery method. The rats in the RES-treated groups were gavaged with RES (50 mg/kg/day) daily for 45 days after the Sham operation or AMI induction; rats in the Sham and AMI groups were gavaged with deionized water. Cardiac function was evaluated by echocardiography. Atrial interstitial fibrosis was assessed by hematoxylin-eosin or Masson’s trichrome staining. Real-time PCR and western blotting analyses were performed to examine the levels of signaling pathway components. Results RES supplementation decreased the inflammatory cytokine levels, improved the cardiac function, and ameliorated atrial interstitial fibrosis in the rats with AMI. Furthermore, RES supplementation inhibited NLRP3 inflammasome activity, decreased the TGF-β1 production, and downregulated the p-SMAD2/SMAD2 expression in the heart. Conclusion RES shows notable cardioprotective effects in a rat model of AMI; the possible mechanisms underlying these effects may involve the improvement of cardiac function and atrial interstitial fibrosis via the RES-mediated suppression of NLRP3 inflammasome activity and inhibition of the TGF-β1/SMAD2 signaling pathway in the heart.

scholarly journals Protective Mechanism of Trimetazidine in Myocardial Cells in Myocardial Infarction Rats through ERK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhenjun Wu ◽  
Lihua Yu ◽  
Xinyue Li ◽  
Xuewen Li
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Infarct Size ◽  
Signaling Pathway ◽  
Dose Group ◽  
Myocardial Infarct ◽  
Erk Signaling ◽  
High Dose ◽  
Myocardial Infarct Size ◽  
Rat Cardiomyocytes

Objective. To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. Methods. 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. Results. Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased ( P < 0.01 ), the cardiac function was significantly improved ( P < 0.01 ), the myocardial infarct size was significantly decreased ( P < 0.01 ), the level of apoptosis was significantly decreased ( P < 0.01 ), the content of ROS in cardiomyocytes was significantly decreased ( P < 0.01 ), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased ( P < 0.01 ), and the expression of Bcl-2/Bax and p-ERK were significantly increased ( P < 0.01 ). Conclusion. Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.

scholarly journals Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunhua Huang ◽  
Yan Zhang ◽  
Hongli Qi ◽  
Xintan Xu ◽  
Lin Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Abstract Background: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail. Methods: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins. Results: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc. Conclusions: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

Sign in / Sign up

Export Citation Format

Share Document