J. Neurochem. (2012) 120, 1048–1059.
Abstract
Etiology of Alzheimer’s disease (AD) is obscure, but neuroinflammation and accumulation of β‐amyloid (Aβ) are implicated in pathogenesis of AD. We have shown anti‐inflammatory and neurotrophic properties of obovatol, a biphenolic compound isolated from Magnolia obovata. In this study, we examined the effect of obovatol on cognitive deficits in two separate AD models: (i) mice that received intracerebroventricular (i.c.v.) infusion of Aβ1–42 (2.0 μg/mouse) and (ii) Tg2576 mice‐expressing mutant human amyloid precursor protein (K670N, M671L). Injection of Aβ1–42 into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. Aβ1–42‐induced abnormality was significantly attenuated by administration of obovatol. When we analyzed with Tg2576 mice, long‐term treatment of obovatol (1 mg/kg/day for 3 months) significantly improved cognitive function. In parallel with the improvement, treatment suppressed astroglial activation, BACE1 expression and NF‐κB activity in the transgenic mice. Furthermore, obovatol potently inhibited fibrillation of Aβin vitro in a dose‐dependent manner, as determined by Thioflavin T fluorescence and electron microscopic analysis. In conclusion, our data demonstrated that obovatol prevented memory impairments in experimental AD models, which could be attributable to amelioration of neuroinflammation and amyloidogenesis by inhibition of NF‐κB signaling pathway and anti‐fibrillogenic activity of obovatol.
IH-901 (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol or compound K) is a final intestinal bacterial metabolite of ginseng in humans. It has various pharmacologic effects such as antiaging, immunopotentiation, antistress, and antimetastatic activities. We analyzed the antioxidant activities of IH-901 using several assays including: total antioxidant activity, reductive potential, 1,1-diphenyl-2-picryl-hydrazyl, hydroxyl, superoxide and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, a nitric oxide scavenging assay and a lipid peroxidation assay. At concentrations of 25 and 100 µg/mL, IH-901 inhibited lipid peroxidation of a linoleic acid emulsion with a potency comparable to ascorbic acid and butylated hydroxyanisole. The reductive potential of IH-901 increased in a concentration-dependent manner. IH-901 exhibited strong DPPH, hydroxyl, superoxide and ABTS radical scavenging activities. IH-901 was also an effective inhibitor of lipid peroxidation, although IH-901 had only a mild scavenging activity against nitric oxide. These results suggest that IH-901 may be a useful antioxidant agent against reactive oxygen species.
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