Jung_2010_Life.Sci_87_420

AIMS: the multifunctional potential of neferine derived from the embryo of Nelumbo nucifera seeds for the age-related neurodegenerative disorders, in vivo anti-amnesic activities and in vitro cholinesterases (ChEs)- and beta-site APP cleaving enzyme 1 (BACE1)-inhibitory activities, as well as anti-inflammatory and antioxidant activities were investigated. MAIN METHODS: in vivo anti-amnesic activities were performed via the passive avoidance, Y-maze, and Morris water maze tasks in a scopolamine-induced amnesia model. The cell-free antioxidant capacities were evaluated by in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals, and peroxynitrite (ONOO(-)), as well as inhibitory activities against nitric oxide (NO), superoxide anion (O(2)(-)), lipid peroxidation, and ONOO(-)-mediated tyrosine nitration. The intracellular antioxidant capacities were also determined via inhibitory activities of lipopolysaccharide (LPS)-induced NO generation and NF-kappaB activation in RAW 264.7 cells. KEY FINDINGS: neferine showed significant improvement in cognitive impairment in scopolamine-induced amnesia animal models and moderate inhibitory activities in ChEs and BACE1 assays. In addition, it exhibited notable scavenging activities against DPPH, ABTS, NO, and O(2)(-) radicals, as well as ONOO(-). Neferine also demonstrated remarkable inhibitory activity against lipid peroxidation and protein nitration in cell-free antioxidant assays and moderate inhibitory activity of NO generation with exceptional suppression of NF-kappaB activation in cell-based assays. SIGNIFICANCE: the results demonstrate that the anti-amnesic effect of neferine may be mediated via antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1.