Allosecurinine Derivative with Two Michael Acceptors Activates Keap1-Nrf2 Pathway
Abstract
Oxidative stress and neuroinflammation drive neurodegenerative diseases, rendering the Keap1-Nrf2 pathway an attractive therapeutic target. Here, we derivatized securinega alkaloids by introducing a 1,4-conjugated Michael acceptor onto the piperidine ring. Among them, 4,5-dehydro-6-oxoallosecurinine, featuring two Michael acceptors (an α,β-unsaturated lactam and an α,β-γ,δ-unsaturated ester), exhibited the most potent Nrf2 activation. This compound promoted Nrf2 nuclear translocation and induced antioxidant and cytoprotective gene expression in microglial cells. In addition, it significantly reduced nitric oxide production and pro-inflammatory cytokine levels in LPS-stimulated microglia. These findings identify securinega alkaloid derivatives as promising Nrf2 activators and support their further evaluation in neuroinflammatory and neurodegenerative disease models.
Fields of Study & Subjects
Phytochemistry and Bioactivity Studies
Plant Toxicity and Pharmacological Properties
Magnolia and Illicium research
Publication details
- Journal / source
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Volume
- 74
- Issue
- 7
- Pages
- 6123–6133
- Publication date
- 11 February 2026
- Language
- EN