Phytochemical Modulation of Oxidative Stress-Inflammation Coupling in Cardiovascular Disease: From Nrf2 and NADPH Oxidases to NLRP3 and Endothelial Dysfunction.
7 affiliations
- 1College of Medicine, Inje University, 75 Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea.
- 2College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
- 3Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy.
- 4IRCCS ISMETT, Department of Research, Via Tricomi 5, 90127 Palermo, Italy.
- 5Thoracic Research Center, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
- 6Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland.
- 7Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, ½ Długa, 61-848 Poznań, Poland.
Abstract
Oxidative stress and inflammation are increasingly recognized as reciprocally reinforcing components of cardiovascular disease rather than independent pathological processes. Their interaction is organized through a network that includes mitochondrial dysfunction, NADPH oxidases (NOX), redox-sensitive NF-κB signaling, NLRP3 inflammasome activation, endothelial nitric oxide synthase (eNOS) uncoupling, and loss of nitric oxide bioavailability. Within this framework, phytochemicals are more appropriately viewed as modulators of endogenous redox-inflammatory signaling than as simple radical scavengers. This review critically examines the evidence linking major phytochemical classes to the Nrf2-NOX-ROS-NF-κB/NLRP3-eNOS/NO axis and evaluates how these mechanisms translate across cardiovascular phenotypes, with emphasis on mechanistic hierarchy, as simultaneous pathway changes may reflect propagation from limited upstream targets rather than direct multi-target activity. The review addresses disease-stage dependence, context-specific roles of Nrf2 and NOX isoforms, mitochondrial-NOX crosstalk, pyroptosis, endothelial dysfunction, and the translational importance of pharmacokinetics, formulation, microbial biotransformation, and drug interactions. Current evidence supports a shift from generalized antioxidant supplementation toward mechanism-matched intervention in biologically selected patients, with the greatest credibility achieved when the active molecular species, dominant mechanism, cardiovascular phenotype, disease stage, clinically relevant exposure, molecular target engagement, functional benefit, and clinical outcomes are evaluated within an integrated framework.
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BibTeX
@article{baek2026phytochemical,
title = {{Phytochemical Modulation of Oxidative Stress-Inflammation Coupling in Cardiovascular Disease: From Nrf2 and NADPH Oxidases to NLRP3 and Endothelial Dysfunction.}},
author = {Siwon Baek and Minseung Kang and Giuseppe Maria Raffa and Calogera Pisano and Vincenzo Nuzzi and Mariusz Kowalewski and Piotr Suwalski and Tomasz Urbanowicz},
journal = {Antioxidants (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/antiox15101222},
url = {https://europepmc.org/article/MED/42939796},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phytochemical Modulation of Oxidative Stress-Inflammation Coupling in Cardiovascular Disease: From Nrf2 and NADPH Oxidases to NLRP3 and Endothelial Dysfunction.
AU - Siwon Baek
AU - Minseung Kang
AU - Giuseppe Maria Raffa
AU - Calogera Pisano
AU - Vincenzo Nuzzi
AU - Mariusz Kowalewski
AU - Piotr Suwalski
AU - Tomasz Urbanowicz
PY - 2026
DA - 2026/09/22
JO - Antioxidants (Basel, Switzerland)
DO - 10.3390/antiox15101222
UR - https://europepmc.org/article/MED/42939796
AB - Oxidative stress and inflammation are increasingly recognized as reciprocally reinforcing components of cardiovascular disease rather than independent pathological processes. Their interaction is organized through a network that includes mitochondrial dysfunction, NADPH oxidases (NOX), redox-sensitive NF-κB signaling, NLRP3 inflammasome activation, endothelial nitric oxide synthase (eNOS) uncoupling, and loss of nitric oxide bioavailability. Within this framework, phytochemicals are more appropriately viewed as modulators of endogenous redox-inflammatory signaling than as simple radical scavengers. This review critically examines the evidence linking major phytochemical classes to the Nrf2-NOX-ROS-NF-κB/NLRP3-eNOS/NO axis and evaluates how these mechanisms translate across cardiovascular phenotypes, with emphasis on mechanistic hierarchy, as simultaneous pathway changes may reflect propagation from limited upstream targets rather than direct multi-target activity. The review addresses disease-stage dependence, context-specific roles of Nrf2 and NOX isoforms, mitochondrial-NOX crosstalk, pyroptosis, endothelial dysfunction, and the translational importance of pharmacokinetics, formulation, microbial biotransformation, and drug interactions. Current evidence supports a shift from generalized antioxidant supplementation toward mechanism-matched intervention in biologically selected patients, with the greatest credibility achieved when the active molecular species, dominant mechanism, cardiovascular phenotype, disease stage, clinically relevant exposure, molecular target engagement, functional benefit, and clinical outcomes are evaluated within an integrated framework.
SN - 2076-3921
ER -