Total flavones of Rhododendron simsii Planch flower protect isolated rat heart from ischaemia-reperfusion injury and its mechanism of UTR-RhoA-ROCK pathway inhibition

J Pharm Pharmacol. 2018 Dec;70(12):1713-1722. doi: 10.1111/jphp.13016. Epub 2018 Sep 25.

Abstract

Objectives: Total flavones of Rhododendron simsii Planch flower (TFR) are an effective part extracted from the flower. The present study was designed to investigate the protective effect of TFR in isolated rat heart following global ischaemia-reperfusion and the possible underlying mechanisms.

Methods: Langendorff perfusion apparatus was used to perfuse isolated rat heart which was subjected to global ischaemia-reperfusion. The hemodynamic parameters were continuously monitored. Coronary flow as well as lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB) and cardiac troponin I (cTnI) in coronary effluents was measured. RhoA activity and urotensin receptor (UTR) and Rho-related coiled-coil-forming protein kinase (ROCK) protein expressions in rat myocardium were examined, respectively. Cardiac dysfunction was indicated by the alterations of hemodynamic parameters and the reduced coronary flow.

Key findings: Total flavones of Rhododendron simsii Planch flower significantly improved ischaemia-reperfusion-induced cardiac dysfunction and leakages of LDH, CK-MB and cTnI, and inhibited myocardial ischaemia-reperfusion-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. The improvement of TFR in the cardiac dysfunction and the leakage of LDH, CK-MB and cTnI were markedly attenuated under the UTR blockade and ROCK inhibition. TFR-inhibited RhoA activity was decreased under the UTR blockade.

Conclusions: Total flavones of Rhododendron simsii Planch flower had a protective effect on ischaemia-reperfusion injury in isolated rat heart, which may be attributed to the blocking of UTR and subsequent inhibition of the RhoA-ROCK pathway.

Keywords: RhoA-ROCK pathway; ischaemia-reperfusion injury; protective effect; total flavones of Rhododendron simsii Planch flower; urotensin receptor.

MeSH terms

  • Animals
  • Coronary Circulation / drug effects
  • Creatine Kinase, MB Form / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Flavones / administration & dosage
  • Flavones / pharmacology*
  • Flowers
  • L-Lactate Dehydrogenase / drug effects
  • Male
  • Myocardial Reperfusion Injury / prevention & control*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Protective Agents
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / drug effects
  • Rhododendron*
  • Troponin I / drug effects
  • Verapamil / pharmacology
  • rho-Associated Kinases / drug effects
  • rhoA GTP-Binding Protein / drug effects

Substances

  • Flavones
  • Plant Extracts
  • Protective Agents
  • Receptors, G-Protein-Coupled
  • Troponin I
  • Verapamil
  • L-Lactate Dehydrogenase
  • rho-Associated Kinases
  • Creatine Kinase, MB Form
  • rhoA GTP-Binding Protein