Cardiac Protective Effect of Astragalus on Viral Myocarditis Mice: Comparison with Perindopril

In clinical practice, Astragali Radix (Astragalus), the root of Astragalus membranaceus Bunge, has been widely applied to treat patients with viral diseases, including viral myocarditis in China. The present study was designed to evaluate the protective effects of Astragalus on the function of sarcoplasmic reticulum calcium ATPase (SERCA2) activity and endothelin system at acute and chronic periods of myocarditis mice induced by CVB 3 infection. Astragalus feeding (2.2 mg/kg/day) could significantly increase the survival rate, alleviate pathological alterations and serum cardiac troponin I (cTnI), as well as restore impaired SERCA activity at the acute stage. Low affinity and capacity of ETR were reversed with Astragalus after the first CVB 3 inoculation up to 7 days and after the second virus inoculation up to 150 days. In the meantime, the contents of cardiac ET-1 and ANP were reduced. Comparison the myocarditis mice treated with Perindopril (0.44 mg/kg/day), an ACE inhibitor, shows that Astragalus achieved a similar effect on survival rate, SERCA2 and ET system. These results indicated that the beneficial effects of Astragalus and Perindopril for treating viral myocarditis might be partly mediated by preserving the functions of SERCA 2 activity and ET system.

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Role of Heart Rate Reduction in the Management of Myocarditis

Current Pharmaceutical Design ◽

10.2174/1381612824666180111105923 ◽

2018 ◽

Vol 24 (3) ◽

pp. 365-378 ◽

Cited By ~ 2

Author(s):

Chen Guang-Yi ◽

Ge Li-Sha ◽

Li Yue-Chun

Keyword(s):

Heart Rate ◽

Nitrosative Stress ◽

Ventricular Remodeling ◽

Animal Experiments ◽

Viral Myocarditis ◽

Protective Effects ◽

Heart Rate Reduction ◽

Rate Reduction ◽

Beneficial Effects ◽

Biological Technique

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

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Targeted deletion of A2A adenosine receptors attenuates the protective effects of myocardial postconditioning

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00612.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. H2523-H2529 ◽

Cited By ~ 50

Author(s):

R. Ray Morrison ◽

Xing Lin Tan ◽

Catherine Ledent ◽

S. Jamal Mustafa ◽

Polly A. Hofmann

Keyword(s):

Functional Recovery ◽

Adenosine Receptor ◽

Adenosine Receptors ◽

Troponin I ◽

Ischemia Reperfusion ◽

Receptor Subtype ◽

Protective Effects ◽

Targeted Deletion ◽

Beneficial Effects ◽

A2a Adenosine Receptors

Endogenous adenosine is an important ligand trigger for the cardioprotective effects of postconditioning (POC), yet it is unclear which adenosine receptor subtype is primarily responsible. To evaluate the role of A2A adenosine receptors in POC-induced protection, global ischemia-reperfusion was performed with and without POC in isolated wild-type (WT) and A2A adenosine receptor knockout (A2AKO) mouse hearts. Injury was measured in terms of postischemic functional recovery and release of cardiac troponin I (cTnI). Activation of protective signaling with POC was assessed by Akt and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. In WT hearts, POC improved recovery of postischemic developed pressure in early (81.6 ± 6.4% of preischemic baseline vs. 37.5 ± 5.6% for non-POC WT at 1 min) and late (62.2 ± 4.2% of baseline vs. 45.5 ± 5.3% for non-POC WT at 30 min) reperfusion, reduced cTnI release by 37%, and doubled the phosphorylation of both Akt and ERK1/2. These beneficial effects of POC were blocked by treatment with the selective A2A adenosine receptor antagonist ZM-241385 during reperfusion. Postischemic functional recovery, cTnI release, and phosphorylation of Akt and ERK1/2 were not different between non-POC WT and A2AKO hearts. In A2AKO hearts, POC did not improve functional recovery, reduce cTnI release, nor increase phosphorylation of Akt or ERK1/2. Thus the protective effects of POC are attenuated by both selective A2A receptor antagonism and targeted deletion of the gene encoding A2A adenosine receptors. These observations support the conclusion that endogenous activation of A2A adenosine receptors is an essential trigger leading to the protective effects of POC in isolated murine hearts.

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Abstract 374: Targeted Deletion of A 2B Adenosine Receptors Attenuates the Protective Effects of Myocardial Postconditioning

Circulation ◽

10.1161/circ.118.suppl_18.s_293-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Xinglin Tan ◽

Stephen L Tilley ◽

Thomas Krahn ◽

Bunyen Teng ◽

S. J Mustafa ◽

...

Keyword(s):

Adenosine Receptor ◽

Troponin I ◽

Diastolic Pressure ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Heart Weight ◽

Receptor Subtypes ◽

Protective Effects ◽

Targeted Deletion ◽

Beneficial Effects

Endogenous adenosine is an important ligand trigger for the cardioprotective effects of postconditioning (PostCon). To assess the hypothesis that A 2B adenosine receptor (A 2B AR) activation contributes to PostCon-induced protection, global ischemia-reperfusion was performed with and without PostCon or the selective A 2B agonist, BAY 60 – 6583 (BAY), in isolated wild-type (WT) and A 2B AR knockout (A 2B KO) mouse hearts. In WT hearts, PostCon improved post-ischemic recovery of left ventricular developed pressure (LVDP) to 63.3±1.6 % of pre-ischemic baseline vs. 49.9±1.6 % in non-PostCon controls (CTL), lowered end diastolic pressure (EDP) to 15.8±1.5 mmHg vs. 27.9±1.6 mmHg in CTL, and reduced coronary efflux of cardiac troponin I (cTnI) to 2507±359 ng/g heart weight vs. 4693±343 ng/g in CTL (n=12 both groups, p <0.05 each comparison). Treatment with BAY in the first two min of reperfusion mimicked beneficial effects of PostCon in WT hearts (LVDP: 64.7±2.0 % baseline, EDP: 16.2±2.0 mmHg, cTnI: 3311±366; n=13, not significant compared to respective PostCon values). Real-time PCR confirmed absence of A 2B AR in A 2B KO hearts and demonstrated no changes in expression of other adenosine receptor subtypes compared with WT hearts. In A 2B KO hearts, neither PostCon nor BAY improved recovery of LVDP (50.8±1.6 % baseline for CTL vs. 54.5±1.7 % with PostCon vs. 53.0±1.4 with BAY; n=6 each group), and neither affected EDP or release of cTnI. During reperfusion, both PostCon and BAY increased survival kinase signaling through Akt and ERK1/2 phosphorylation in WT but not A 2B KO hearts. In non-ischemic WT hearts, Akt and ERK1/2 phosphorylation was increased by both BAY treatment and application of the PostCon stimulus. These data demonstrate that the protective effects of PostCon are attenuated by targeted deletion of A 2B AR and are mimicked by selective A 2B AR activation, suggesting A 2B AR activation is an important trigger leading to PostCon-induced myocardial protection.

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Protective Effect of Silymarin against Acrolein-Induced Cardiotoxicity in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/352091 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 18

Author(s):

Elahe Taghiabadi ◽

Mohsen Imenshahidi ◽

Khalil Abnous ◽

Fatemeh Mosafa ◽

Mojtaba Sankian ◽

...

Keyword(s):

Protective Effect ◽

Caspase 3 ◽

Troponin I ◽

Environmental Pollutants ◽

Protective Effects ◽

Histopathological Changes ◽

Cardiac Tissues ◽

Creatine Kinase Mb ◽

Serum Cardiac Troponin ◽

Cytosolic Cytochrome

Reactiveα,β-unsaturated aldehydes such as acrolein (ACR) are major components of environmental pollutants and have been implicated in the neurodegenerative and cardiac diseases. In this study, the protective effect of silymarin (SN) against cardiotoxicity induced by ACR in mice was evaluated. Studies were performed on seven groups of six animals each, including vehicle-control (normal saline + 0.5% w/v methylcellulose), ACR (7.5 mg/kg/day, gavage) for 3 weeks, SN (25, 50 and 100 mg/kg/day, i.p.) plus ACR, vitamin E (Vit E, 100 IU/kg, i.p.) plus ACR, and SN (100 mg/kg, i.p.) groups. Mice received SN 7 days before ACR and daily thereafter throughout the study. Pretreatment with SN attenuated ACR-induced increased levels of malondialdehyde (MDA), serum cardiac troponin I (cTnI), and creatine kinase-MB (CK-MB), as well as histopathological changes in cardiac tissues. Moreover, SN improved glutathione (GSH) content, superoxide dismutase (SOD), and catalase (CAT) activities in heart of ACR-treated mice. Western blot analysis showed that SN pretreatment inhibited apoptosis provoked by ACR through decreasing Bax/Bcl-2 ratio, cytosolic cytochrome c content, and cleaved caspase-3 level in heart. In conclusion, SN may have protective effects against cardiotoxicity of ACR by reducing lipid peroxidation, renewing the activities of antioxidant enzymes, and preventing apoptosis.

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Hydrogen Sulfide Inhalation Improves Neurological Outcome via NF-κB-Mediated Inflammatory Pathway in a Rat Model of Cardiac Arrest and Resuscitation

Cellular Physiology and Biochemistry ◽

10.1159/000430316 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1527-1538 ◽

Cited By ~ 18

Author(s):

Xia Wei ◽

Bing Zhang ◽

Yu Zhang ◽

Hangbing Li ◽

Long Cheng ◽

...

Keyword(s):

Cardiac Arrest ◽

Hydrogen Sulfide ◽

Survival Rate ◽

Ventricular Fibrillation ◽

Inflammatory Reaction ◽

Neurological Outcome ◽

Neuronal Loss ◽

Protective Effects ◽

Beneficial Effects ◽

Proinflammatory Mediators

Background/Aims: The effects of H2S on cerebral inflammatory reaction after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) remain poorly understood. In this study, we investigated the effects of exogenous 40 ppm and 80 ppm H2S gas on inflammatory reaction and neurological outcome after CA/CPR. Methods: CA was induced by ventricular fibrillation and followed by CPR. Forty or 80 ppm H2S was inhaled for 1 h immediately following CPR. The levels of IL-1ß, IL-6 and TNF-a, the myeloperoxidase (MPO) activity, the expression of iNOS and ICAM-1, and the phosphorylation and translocation of NF-κB were evaluated at 24 h after CA/CPR. The tape removal test, survival rate and hippocampal neuronal counts were investigated at 14 d after CA/CPR. Results: CA/CPR induced significant increases in IL-1ß, IL-6, TNF-a and MPO activity. The phosphorylation and translocation of NF-κB, and the expression of iNOS and ICAM-1 were increased significantly. Inhalation of 40 or 80 ppm H2S gas decreased these inflammatory cytokines. Furthermore, 40 or 80 ppm H2S inhibited the activation of NF-κB and the downstream proinflammatory mediators iNOS and ICAM-1. H2S inhalation also improved neurological function, 14-d survival rate, and reduced hippocampal neuronal loss. Conclusion: These results indicated that inhalation of H2S protected against brain injury after CA/CPR. The mechanisms underlying protective effects of H2S were associated with the inhibition of CA/CPR-induced inflammation reactions by reducing IL-1ß, IL-6 and TNF-a, and concomitantly inhibiting the activation and infiltration of neutrophils. The beneficial effects of H2S might be mediated by downregulation of NF-κB and the downstream proinflammatory signaling pathway.

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Peripheral Blood MicroRNAs as Potential Biomarkers of Myocardial Damage in Acute Viral Myocarditis

Genes ◽

10.3390/genes12030420 ◽

2021 ◽

Vol 12 (3) ◽

pp. 420

Author(s):

Maria Marketou ◽

Joanna Kontaraki ◽

Alexandros Patrianakos ◽

George Kochiadakis ◽

Ioannis Anastasiou ◽

...

Keyword(s):

Peripheral Blood ◽

Mononuclear Cells ◽

Troponin I ◽

Left Ventricular Systolic Dysfunction ◽

Global Longitudinal Strain ◽

Viral Myocarditis ◽

Myocardial Damage ◽

Left Ventricular ◽

Cardiovascular Development ◽

Acute Viral Myocarditis

Background: microRNAs (miRs) have emerged as important modulators of cardiovascular development and disease. Our aim was to determine whether cardiac-related miRs such as miR-21-5p and miR-1-3p were differentially expressed in acute viral myocarditis and whether any of them was related with the extent of myocardial damage and left ventricular dysfunction. Methods: We enrolled 40 patients with acute viral myocarditis. Blood samples were taken on admission and miRs expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Results: miR-21-5p, miR-1-3p were significantly elevated in acute myocarditis. miR-21-5p levels showed a strong correlation with global longitudinal strain (r = 0.71, p < 0.01), while miR-1-3p had significant correlations with troponin I (r = 0.79, p < 0.01). Conclusions: The expression of miR-21-5p and miR-1-3p in peripheral blood is increased in acute viral myocarditis, and this increase is correlated with myocardial damage and indicative of left ventricular systolic dysfunction in these patients.

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Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19082180 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2180 ◽

Cited By ~ 5

Author(s):

María Ariza ◽

Tamara Forbes-Hernández ◽

Patricia Reboredo-Rodríguez ◽

Sadia Afrin ◽

Massimiliano Gasparrini ◽

...

Keyword(s):

Biological Activity ◽

Oxidative Damage ◽

Hepg2 Cells ◽

In Vitro Digestion ◽

Protective Effects ◽

Beneficial Effects ◽

Positive Effects ◽

Digestion Process ◽

Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

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An Evaluation of the Possible Protective Effects of Neonatal Striatal Transplants Against Kainic Acid-Induced Lesions

Journal of Neural Transplantation ◽

10.1155/np.1991.75 ◽

1991 ◽

Vol 2 (1) ◽

pp. 75-79 ◽

Cited By ~ 1

Author(s):

David R. Nash ◽

Stanley M. Kaplan ◽

Andrew B. Norman ◽

Paul R. Sanberg

Keyword(s):

Survival Rate ◽

Kainic Acid ◽

Protective Effects ◽

Striatal Neurons ◽

Tissue Transplants ◽

Significant Difference

The present study examined the recent report that transplantation of neonatal striatal tissue into kainic acid (KA) lesioned striatum protected the contralateral striatum from a subsequent KA lesion. We did not find a significant difference in the survival rate of animals that received neonatal striatal transplants into a KA lesioned striatum followed by a subsequent lesion of the contralateral striatum compared to those animals that received bilateral KA-induced striatal lesions alone. The tissue transplants did not protect against the degeneration of striatal neurons induced by KA. Indeed, the survival rate was very low (25%) in the transplant groups. A second experiment was also performed to examine whether a neonatal striatal transplant might reduce the severe syndrome of aphagia and adipsia associated with KA lesions of the striatum. Animals that received the neonatal striatal transplants showed increased aphagia and adipsia compared to animals only receiving the KA lesion. Again, the transplant group had a very low survival rate (10%). The present study was unable to confirm that neonatal striatal transplants protect against KA lesions either by themselves or in conjunction with a recent KA lesion.

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