1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis

Pharmacol Res. 2022 Jun:180:106151. doi: 10.1016/j.phrs.2022.106151. Epub 2022 Mar 2.

Abstract

For the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hypertrophy that closely resembles heart defects associated with PAH and validated our in vitro findings on a preclinical in vivo model of monocrotaline (MCT)-induced PAH. Our results showed the in vitro antihypertrophic effect of 1,8-cineole, a monoterpene widely found in several essential oils. Also, a decrease in RV hypertrophy and fibrosis, and an improvement in heart function in vivo was observed, when 1,8-cineole was applied topically. Furthermore, 1,8-cineole restored gap junction protein connexin43 distribution at the intercalated disks and mitochondrial functionality, suggesting it may act by preserving cardiac cell-to-cell communication and bioenergetics. Overall, our results point out a promising therapeutic compound that can be easily applied topically, thus paving the way for the development of effective cardiac-specific therapies to greatly improve PAH outcomes.

Keywords: 1,8-Cineole; 1,8-Cineole (PubChem CID: 2758); Connexin43; Fibrosis; Hypertrophy; Mitophagy; Right ventricle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies*
  • Connexin 43
  • Disease Models, Animal
  • Eucalyptol / therapeutic use
  • Heart Ventricles / metabolism
  • Homeostasis
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Hypertrophy, Right Ventricular / metabolism
  • Pulmonary Arterial Hypertension* / drug therapy
  • Ventricular Dysfunction, Right* / metabolism

Substances

  • Connexin 43
  • Eucalyptol