Screening of natural compounds as activators of the keap1-nrf2 pathway.
Level 5 - mechanism / opinion, no new human data
In vitro cell-based reporter assay (bench research)
PubMed 24310212 · doi:10.1055/s-0033-1351097
What was done
Researchers screened a library of 54 natural compounds to evaluate their capacity to activate the Keap1-Nrf2 cytoprotective pathway. The screen used AREc32 reporter cells containing a luciferase gene regulated by antioxidant response element promoters. Each compound was tested across 13 concentrations between 0.02 and 30 µM. Tert-butylhydroquinone and 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide were tested in parallel as positive controls.
What was found
Among the controls, 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide was the most potent compound overall, with an EC50 of 0.41 µM. Among the 54 natural compounds tested, andrographolide showed the highest efficacy, followed in rank order by trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and carnosol, all demonstrating higher efficacy than tert-butylhydroquinone. Seven natural compounds (andrographolide, trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and cafestol) had lower EC50 values (higher potency) than tert-butylhydroquinone, though all were less potent than 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide. Exact numerical EC50 and efficacy values for individual natural compounds were not provided in the abstract.
Why it matters
This study provides a comparative in vitro ranking of 54 natural dietary compounds for Keap1-Nrf2 pathway activation against established benchmark chemical activators.
Limits
The study is restricted to an in vitro reporter cell line assay without human or animal in vivo data. Bioavailability, compound metabolism, endogenous antioxidant enzyme induction, and physiological toxicity were not evaluated.
Cited by
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