Polyphenol antioxidant pathways

Polyphenol antioxidant pathways represent a complex network of signaling cascades through which dietary polyphenols, such as curcumin and resveratrol, exert their cytoprotective and anti-inflammatory effects. The most prominent mechanism is the activation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which induces the expression of antioxidant response element (ARE)-regulated genes, including heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) (Gastroenterology, 2011, 141:1572-85). Additionally, these pathways often involve the activation of Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), which are critical for mitochondrial biogenesis and metabolic homeostasis. By modulating these pathways, polyphenols help neutralize reactive oxygen species (ROS) and inhibit pro-inflammatory transcription factors like NF-κB, thereby protecting against oxidative stress-induced cellular damage (Biochemistry and Pharmacology, 1987, 36:317-322). These pathways are considered significant therapeutic targets for chronic conditions such as neurodegenerative diseases, cardiovascular disorders, and metabolic syndrome. However, the clinical utility of targeting these pathways is frequently hampered by the low systemic bioavailability of natural polyphenols and the potential for non-specific interactions with multiple cellular targets. As a broad category of signaling cascades rather than a single molecular entity, these pathways represent a therapeutic focus rather than a discrete target.

Other names

Polyphenolic antioxidant signalingNrf2-ARE pathwayPhytochemical antioxidant responsePolyphenol-mediated cytoprotective pathways

Activation of the Nrf2/ARE signaling axis, induction of phase II antioxidant enzymes, activation of SIRT1/AMPK pathways, and inhibition of NF-κB-mediated inflammation.