Protective effects of grape seed proanthocyanidin extracts on cerebral cortex of streptozotocin-induced diabetic rats through modulating AGEs/RAGE/NF-kappaB pathway.
Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-kappaB p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-kappaB p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-kappaB p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-kappaB p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-kappaB pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.
Lu
Mei
M
Key Laboratory of Cardiovascular Proteomics of Shandong Province, Jinan, China.
Xu
Ling
L
Li
Baoying
B
Zhang
Weidong
W
Zhang
Chengmei
C
Feng
Hong
H
Cui
Xiaopei
X
Gao
Haiqing
H
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000187:drug effects; D001928:Brain Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects*; D048909:Diabetes Complications / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism*; D056604:Grape Seed Extract / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013311:Streptozocin; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D016328:NF-kappa B; D044945:Proanthocyanidins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin