Polyphenols modulate key molecular pathways reducing inflammation, fibrosis, and endothelial dysfunction in HFpEF, but clinical efficacy is limited by low bioavailability and lack of trials.
Do polyphenols attenuate key pathways implicated in the progression of HFpEF?
Polyphenols offer a biologically plausible adjuvant therapy for HFpEF by targeting inflammation, oxidative stress, and metabolic pathways, but require high-quality clinical trials to validate efficacy.
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Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome driven by systemic inflammation, persistent oxidative stress, endothelial dysfunction, and impaired mitochondrial bioenergetics. Despite recent therapeutic advances, the management of these specific pathophysiological mechanisms remains a challenge. Polyphenols, bioactive compounds found in plants, have emerged as potential modulators of these pathways. Objective: This review critically summarizes the pathophysiological and molecular evidence supporting the role of polyphenols—specifically phenolic acids, flavonoids, and lignans—in attenuating key pathways implicated in the progression of HFpEF, while also addressing the current limitations in clinical translation. Results: Preclinical evidence indicates that polyphenols regulate cellular homeostasis by activating the Keap1/Nrf2 antioxidant axis and AMPK/SIRT1 metabolic pathways, while inhibiting NF-κB-mediated pro-inflammatory signals and TGF-β fibrotic pathways. These molecular actions collectively preserve endothelial function via PI3K/Akt/eNOS, reduce interstitial fibrosis, and improve myocardial metabolic efficiency. Furthermore, the modulation of gut microbiota amplifies these systemic effects, particularly in obesity-related phenotypes. However, direct clinical application is currently hindered by low bioavailability and a scarcity of randomized trials specifically in HFpEF populations. Polyphenols represent a promising and biologically plausible nutritional therapeutic axis for the multidimensional management of HFpEF. While the molecular rationale is strong, future research should focus on improving bioavailability and conducting high-quality clinical trials to validate efficacy as an adjuvant therapy.
Medeiros et al. (Wed,) reported a other. Polyphenols modulate key molecular pathways reducing inflammation, fibrosis, and endothelial dysfunction in HFpEF, but clinical efficacy is limited by low bioavailability and lack of trials.