Anthocyanin attenuates pulmonary arterial hypertension and associated heart failure via improving mitochondrial function through Nrf2-dependent mechanism

Clin Exp Hypertens. 2025 Dec;47(1):2503805. doi: 10.1080/10641963.2025.2503805. Epub 2025 May 9.

Abstract

Background: Mitochondrial dysfunction of pulmonary vascular endothelial cells is one of the important pathogenesis of pulmonary arterial hypertension (PAH). Anthocyanin can protect mitochondrial function, but whether anthocyanin can prevent PAH and its related mechanism has not been reported.

Methods: Using rodent PAH models induced by chronic hypoxia for 21 days, we investigated the changes of hemodynamics, histopathology and vascular endothelial function after anthocyanin treatment for 21 days.

Results: We found that anthocyanin treatment improved pulmonary endothelial function, vascular remodeling and associated right heart failure. Mechanistically, we found that anthocyanin treatment promoted the nucleus translocation of Nrf2 and improved the impaired mitochondrial function. The beneficial effects of anthocyanin on regulation of mitochondrial function were abolished by inhibition of Nrf2. Finally, in Nrf2 deficient mice, the protective effects of anthocyanin on PAH were largely vanished.

Conclusions: Collectively, we showed that anthocyanin attenuated PAH and associated right heart failure via improving mitochondrial function through Nrf2-dependent mechanism, suggesting that anthocyanin may represent a novel therapeutic potential for PAH.

Keywords: Anthocyanin; Nrf2; mitochondrial function; pulmonary arterial hypertension; right heart failure.

MeSH terms

  • Animals
  • Anthocyanins* / pharmacology
  • Anthocyanins* / therapeutic use
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Heart Failure* / drug therapy
  • Heart Failure* / etiology
  • Heart Failure* / metabolism
  • Heart Failure* / physiopathology
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Arterial Hypertension* / metabolism
  • Rats
  • Vascular Remodeling / drug effects

Substances

  • Anthocyanins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse