Fermented Noni Juice Supplementation Attenuates Heart Failure Development in Mice: Involvement of the Pentose Phosphate Pathway

ABSTRACT Morinda citrifolia L., commonly known as Noni, is a traditional medicinal plant that has long been utilized in various cultures for its anti‐inflammatory and antioxidant properties. Heart failure (HF) is a significant and growing public health concern worldwide that is characterized by substantial morbidity, mortality, and healthcare costs. However, the relationship between Noni and HF is unknown. In this study, we employed a well‐established preclinical HF model to comprehensively evaluate the cardioprotective effects of Noni. We found that fermented Noni juice administration significantly prevented cardiac diastolic dysfunction, hypertrophy, and fibrosis, and markedly reduced inflammation and oxidative stress in HF. Mechanistically, fermented Noni juice was associated with increased accumulation of pentose phosphate pathway intermediates and enhanced NADPH production. This metabolic shift effectively boosts the cellular antioxidant defense system, leading to a robust antioxidant stress response that ultimately mitigates key drivers of HF progression. Collectively, these findings suggest that the cardioprotective effects of fermented Noni juice may involve modulation of the pentose phosphate pathway.