Aβ-IN-6 is an orally active compound exhibiting anti-inflammatory, antioxidant, and anti-oligomeric activities, with significant implications for Alzheimer's disease (AD) research [1]. It effectively reduces the release of pro-inflammatory cytokines from microglia cells, promotes Nrf2 nuclear translocation, and impedes the formation of Aβ oligomers. Furthermore, Aβ-IN-6 demonstrates a stable neuroprotective effect by modulating redox-sensitive signaling pathways in an in vivo oxidative stress model.

Aβ-IN-6 (Compound 4; 1-20 μM; 24 hours) significantly reduces microglial cell viability starting at a concentration of 5 μM [1]. At concentrations above 2.5 μM, Aβ-IN-6 (1.25-40 μM; 24 hours) shows notable cytotoxicity in SH-SY5Y neuroblastoma cells [1]. Aβ-IN-6 (2.5 μM; 3 hours) significantly induces Nrf2 nuclear translocation [1]. Aβ-IN-6 at 2.5 μM significantly inhibits the increase in levels of two cytokines and NLRP3 mRNA induced by LPS [1]. With pre-treatment of 1 and 2.5 μM for 1 hour followed by LPS stimulation for 24 hours, Aβ-IN-6 considerably reduces the release of TNF-α and IL-1β induced by LPS [1]. Pre-treatment with Aβ-IN-6 (2.5 μM; 24 hours) prior to exposure to tert-butyl hydrogen peroxide (t-BuOOH; 50 μM for 30 minutes) reduces ROS formation by approximately 18% [1].

Aβ-IN-6 (Compound 4; 10 μM; added to standard food) effectively reduced the elevated levels of ROS in the muscles and brains of larvae with neurodegenerative disease (D-spastin loss-of-function model) back to the control levels observed in the Spastin fruit fly model [1].