Isolation and neuronal apoptosis inhibitory property of bacoside-A3 via downregulation of ß-amyloid induced inflammatory response.

ABSTRACT

Alzheimer's disease is one of the neurodegenerative disorders caused by neuronal degeneration and apoptosis in brain. Bacoside A and B isolated from the Bacopa monniera plant are responsible for cognitive effects. These compounds repair damaged neurons by promoting activity of kinases, synaptic activity restoration, and improvement of nerve transmission. The present study explored the effect of bacoside-A3 on ß-amyloid-induced reduction of U87MG cell viability, generation of oxidative radicals, and activation of nuclear factor-κB. The U87MG cells were stimulated with ß-amyloid (10 µM) after 24 h of bacoside-A3 pretreatment or without pretreatment to induce characteristics of Alzheimer disease in vitro. Sulforhodamine B (SRB) assay was used to count viable cells and ELISA kit for analysis of PGE2 secretion. The pretreatment with bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell proliferation. Pretreatment of U87MG cells with bacoside-A3 prior to ß-amyloid stimulation suppressed generation of ROS in a concentration-based manner. The ß-amyloid-mediated formation of iNOS in U87MG cells was suppressed by bacoside-A3 in a dose-based manner. The ß-amyloid-mediated PGE2 secretion was suppressed by bacoside-A3 pretreatment in U87MG cells in the dose-based manner. The overexpression of COX-2 by ß-amyloid stimulation was suppressed in bacoside-A pretreated cells in the dose-based manner. The bacoside-A3 pretreatment prevented nuclear translocation of NF-κB in U87MG cells in the dose-based manner. In summary, bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell viability, inhibited generation of oxidative radicals, PGE2, and synthesis of iNOS. Therefore, bacoside-A3 has therapeutic potential for Alzheimer disease and further in vivo studies need to be performed.