Neuroprotective Effects of Asparagus officinalis Stem Extract in Transgenic Mice Overexpressing Amyloid Precursor Protein.

To mimic Alzheimer's disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid ß, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid ß, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid ß, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.

Syndecan 1 plays a novel role in enteral glutamine's gut-protective effects of the postischemic gut.

Syndecan 1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells and, like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan 1 would abrogate the gut-protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia-reperfusion (IR) was utilized. In vitro, intestinal epithelial cells underwent hypoxia-reoxygenation to mimic gut IR with 2 mM (physiologic) or 10 mM glutamine supplementation. Permeability, caspase activity, cell growth, and cell surface and shed syndecan 1 were assessed. In vivo, wild-type and syndecan 1 knockout (KO) mice received ± enteral glutamine followed by gut IR. Intestinal injury was assessed by fluorescent dye clearance and histopathology, permeability as mucosal-to-serosal clearance ex vivo in everted sacs, and inflammation by myeloperoxidase (MPO) activity. In an in vitro model of gut IR, glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed syndecan 1 was reduced by glutamine without an increase in syndecan 1 mRNA. In vivo, intestinal permeability, inflammation, and injury were increased after gut IR in wild-type mice and further increased in syndecan 1 KO mice. Glutamine's attenuation of IR-induced intestinal hyperpermeability, inflammation, and injury was abolished in syndecan 1 KO mice. These results suggest that syndecan 1 plays a novel role in the protective effects of enteral glutamine in the postischemic gut.