Dietary Flavonoids as Cross-System Modulators of Hypertension and Intestinal Permeability

Abstract

Hypertension (HTN) and intestinal permeability (IP) are increasingly recognized as interrelated processes driven by shared oxidative and inflammatory mechanisms. This review synthesizes evidence linking HTN-induced vascular dysfunction to alterations in intestinal barrier integrity and explores the potential of dietary flavonoids as modulators of these pathologies. A narrative approach was used to synthesize findings from cellular, animal, and human studies that specifically address how flavonoids influence the molecular pathway connecting HTN and IP. Emerging evidence suggests that HTN-driven vascular injury, which is characterized by reduced nitric oxide bioavailability, increased reactive oxygen species, and pro-inflammatory signaling, contributes to tight junction disruption and increased IP. Mechanistic evidence indicates that flavonoids exert both direct antioxidant effects and indirect actions via the modulation of key cellular pathways. Preclinical and clinical data demonstrate that flavonoid-rich foods and isolated compounds can lower blood pressure, enhance endothelial function, and preserve intestinal barrier integrity by stabilizing tight junction proteins and attenuating pro-inflammatory signaling. Together, these findings highlight flavonoids as cross-system modulators that may mitigate HTN-associated increases in IP. Further research addressing sex, race, and age differences, as well as flavonoid bioavailability and dose optimization, is needed to clarify their translational potential.