HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Fargesin as a potential β₁ adrenergic receptor antagonist protects the hearts against ischemia/reperfusion injury in rats via attenuating oxidative stress and apoptosis.

Abstract
Fargesin displayed similar chromatographic retention peak to metoprolol in the cardiac muscle/cell membrane chromatography (CM/CMC) and β1 adrenergic receptor/cell membrane chromatography (β1AR/CMC) models. To provide more biological information about fargesin, we investigated the effects of fargesin on isoproterenol-(ISO-) induced cells injury in the high expression β1 adrenergic receptor/Chinese hamster ovary-S (β1AR/CHO-S) cells and occluding the left coronary artery- (LAD-) induced myocardial ischemia/reperfusion (MI/R) injury in rats. The results in vitro showed that ISO-induced canonical cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) levels were decreased by fargesin in β1AR/CHO-S cells. Fargesin attenuated the serum creatine kinase (CK), lactate dehydrogenase (LDH), and improved histopathological changes of ischemic myocardium compared with the I/R rats. Similar results were obtained with Evans Blue/TTC staining, in which fargesin notably reduced infarct size. Moreover, compared with the I/R group, fargesin increased COX release and the activities of some endogenous antioxidative enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), but suppressed malondialdehyde (MDA), and intracellular ROS release. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated fargesin suppressed myocardial apoptosis, which may be related to inhibition of caspase-3 activity. Taken together, these results provided substantial evidences that fargesin as a potential β1AR antagonist through cAMP/PKA pathway could protect against myocardial ischemia/reperfusion injury in rats. The underlining mechanism may be related to inhibiting oxidative stress and myocardial apoptosis.
AuthorsXin Wang, Yongjie Cheng, Hui Xue, Yuan Yue, Weifang Zhang, Xiaoni Li
JournalFitoterapia (Fitoterapia) Vol. 105 Pg. 16-25 (Sep 2015) ISSN: 1873-6971 [Electronic] Netherlands
PMID26025856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015. Published by Elsevier B.V.
Chemical References
  • Adrenergic beta-1 Receptor Antagonists
  • Benzodioxoles
  • Cardiotonic Agents
  • Lignans
  • Reactive Oxygen Species
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Creatine Kinase
  • fargesin
Topics
  • Adrenergic beta-1 Receptor Antagonists (pharmacology)
  • Animals
  • Apoptosis (drug effects)
  • Benzodioxoles (pharmacology)
  • CHO Cells
  • Cardiotonic Agents (pharmacology)
  • Catalase (metabolism)
  • Creatine Kinase (blood)
  • Cricetulus
  • Disease Models, Animal
  • Glutathione Peroxidase (metabolism)
  • Heart (drug effects)
  • L-Lactate Dehydrogenase (blood)
  • Lignans (pharmacology)
  • Malondialdehyde (metabolism)
  • Molecular Structure
  • Myocardium (pathology)
  • Oxidative Stress (drug effects)
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species (metabolism)
  • Reperfusion Injury (drug therapy)
  • Superoxide Dismutase (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: