Neuroprotection of aucubin in primary diabetic encephalopathy.
Hippocampal neuronal apoptosis accompanied by impairment of cognitive function occurs in primary diabetic encephalopathy. In this study, we investigated the neuroprotective mechanism of the iridoid glycoside, aucubin, using rats (n=8). Diabetes mellitus was induced in the rats by intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg body weight). After 65 d, half of the DM rats were administered aucubin (5 mg/kg; i.p.) for 15 d, yielding treatment DM+A. A third group of rats received no streptozotocin or aucibin, and served as controls (CON). Encephalopathy was assessed using Y-maze behavioral testing. Rats were euthanized on Day 87, and hippocampi were excised for visual (light and transmission electron microscopic) and immunochemical (Western blot; immunohistochemical) assessments of the CA1 subfield for apoptosis and expression of regulatory proteins Bcl-2 and Bax. Treatment responses to all the parameters examined (body weight, plasma glucose, Y-maze error rates, pyramidal cell ultrastructure, proportions of apoptotic cells, levels of expression of Bcl-2 and Bax, and survivability of neuronal cells) were identical: there were highly significant differences between DM and CON groups (P<0.001), but the effects were significantly moderated (P<0.01) in DM+A compared with DM. These findings confirm the association of apoptosis with the encephalopathic effects of diabetes mellitus, and suggest a major role of the expression levels of Bcl-2 and Bax in the regulation of apoptotic cell death. All of the results suggest that aucubin could effectively inhibit apoptosis by modulating the expressions of Bcl-2 and Bax genes.
Xue
HongYu
H
Department of Bioscience and Biotechnology, Dalian University of technology, Dalian 116024, China.
Jin
LiJi
L
Jin
Lei
L
Zhang
Peng
P
Li
DanQing
D
Xia
YanQiu
Y
Lu
YaNan
Y
Xu
YongPing
Y
D000818:Animals; D015153:Blotting, Western; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005960:Glucosides / Q000627:therapeutic use*; D007150:Immunohistochemistry; D057888:Iridoid Glucosides; D039823:Iridoids / Q000627:therapeutic use*; D008297:Male; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; D018696:Neuroprotective Agents; C006650:aucubin