Nrf2: Master Regulator of Antioxidants

Nrf2 (Nuclear factor erythroid 2-related factor 2) is the master transcription factor for endogenous antioxidants. Activated in response to oxidative stress, it triggers the production of glutathione, superoxide dismutase (SOD), catalase, glutathione peroxidase, and heme oxygenase-1. It is one of the main cellular defense mechanisms.

Activation Mechanism

1. At rest, Nrf2 is bound to Keap1 (cytoplasmic sequestration)
2. Oxidative stress modifies Keap1 → Nrf2 release
3. Nrf2 translocates to the nucleus
4. Binding to ARE (Antioxidant Response Elements)
5. Transcription of antioxidant genes

Nrf2 Target Genes

• Glutathione-S-transferase (GST)
• γ-glutamyl-cysteine ligase (glutathione synthesis)
• Superoxide dismutase (SOD)
• Catalase
• NAD(P)H quinone oxidoreductase 1 (NQO1)
• Heme oxygenase-1 (HO-1)

Pathologies with Underactive Nrf2

• Neurodegenerative diseases (Alzheimer's, Parkinson's, ALS)
• COPD and pulmonary fibrosis
• Cataracts and AMD
• Accelerated aging
• Sarcopenia

Natural Nrf2 Activators

• [6]-gingerol: documented Nrf2 activator
• Curcumin: powerful Nrf2 activator
• Sulforaphane (broccoli): the most powerful natural activator
• Piperine: potentiates curcumin's effect on Nrf2
• Capsaicin: moderate activation

Nrf2 and INTI

INTI activates Nrf2 through several complementary ingredients (ginger, turmeric, capsaicin). It supports endogenous antioxidant defenses — particularly useful in: intense sport, pollution, aging, chronic diseases.