Quinone reductase inducing polyacetylenes of the Araliaceae: Effects of structure and configuration on activity

Consumption of „indirect antioxidants“– compounds that increase the production of antioxidant proteins in vivo – is a promising means to prevent or delay diseases in which oxidative stress plays an underlying role. Indeed, indirect antioxidants show potent protective action in animal models of cancer, cardiovascular disease, Parkinson's disease and ischemia. Indirect antioxidants act by increasing the activity of Nrf2, a transcription factor responsible for the constitutive and inducible expression of antioxidant and detoxifying proteins such as quinone reductase (QR), heme oxygenase-1 and superoxide dismutase. In order to identify novel activators of Nrf2, we used the activity of the representative enzyme, QR, as a guide to isolate the active components from the methanolic extracts of two members of the Araliaceae from Canada, Oplopanax horridus and Aralia nudicaulis. Several related polyacetylenes with potent activity were isolated and a number of structure activity-relationships were observed. Importantly, the stereochemical configuration of these compounds directly impacted their relative potencies as QR inducing agents.