Kim, Seoyoung Kim, Rium Chu, Taejin Park, Jong-Hyun Park, Ki Duk Han, Sunkyu 2026-02-26T03:00:04Z 2026-02-26T03:00:04Z 2026-02-26 2026-02 0021-8561 https://pubs.kist.re.kr/handle/201004/154365 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. English American Chemical Society Allosecurinine Derivative with Two Michael Acceptors Activates Keap1-Nrf2 Pathway Article 10.1021/acs.jafc.5c09138 1 Journal of Agricultural and Food Chemistry, v.74, no.7, pp.6123 - 6133 Journal of Agricultural and Food Chemistry 74 7 6123 6133 N scie scopus 001687321300001 Agriculture, Multidisciplinary Chemistry, Applied Food Science & Technology Agriculture Chemistry Food Science & Technology Article; Early Access OXIDATIVE STRESS REDOX ANTIOXIDANT GENES securinega alkaloids Flueggeasuffruticosa plant structure-activity relationship antioxidant reagent anti-inflammatory reagent chemical modification Keap1-Nrf2 pathway