Caffeic Acid Phenethyl Ester (CAPE) Prevents Development of STZ-ICV Induced dementia in Rats

BACKGROUND: Chronic oxidative stress and inflammation severely affect the normal physiology of neurons and lead to neurodegenerative disorders such as Alzheimer's disease (AD). Polyphenols proved a boon in the prevention of dementia due to their antioxidant and neuroprotective potential. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound attributed with antioxidant, immunomodulatory, and neuroprotective properties. OBJECTIVE: The present study investigates the effect of CAPE on experimental dementia in rats. METHODS: Intracerebroventricle (ICV) injection of streptozotocin (STZ; 3 mg/kg) was given to Wistar rats (200 g, either sex) on days 1 and 3 to induce dementia of AD type. CAPE (3 and 6 mg/kg, i.p.) was administered to separate groups of rats for 28 successive days daily. Morris water maze and elevated plus maze served as exteroceptive behavioral models to measure the memory of the rats. RESULTS: The present study illustrated that CAPE treatment for 28 consecutive days arrested the development of cognitive deficits in STZ-ICV-treated rats, that is, a significant (P < 0.05) reduction in the mean escape latency during acquisition trial and increased (P < 0.05) time spent in target quadrant during retrieval trial in Morris water maze test and reduction (P < 0.05) in transfer latency in elevated plus maze test. Furthermore, both the doses of CAPE when administered to rats that were previously treated with STZ-ICV prevented the rise of brain thiobarbituric acid reactive substance as well as TNF-α and simultaneously enhanced the GSH content. CONCLUSION: CAPE administration ameliorated STZ-ICV-induced dementia through the attenuation of oxidative stress and inflammation. SUMMARY: Intracerebroventricular administration of streptozotocin (STZ-ICV) induced cognitive deficits, enhanced brain oxidative stress as well as inflammation in rats. Treatment with Caffeic Acid Phenethyl Ester (CAPE; dose 3 and 6 mg/kg, i.p.) for 28 days once daily, enhanced the memory and prevented the development of STZ-ICV-induced dementia in rats. The CAPE treated rats showed decrease in mean escape latency and increase in time spent in target quadrant in Morris Water Maze test. A decline in transfer latency of CAPE treated rats was observed in Elevated Plus Maze model. Profound rise in brain GSH levels and diminution of TBARS as well as TNF-α content was observed in brains of CAPE treated rats. Hence, the memory enhancing activity of CAPE against STZ-ICV-induced dementia is attributed to its robust antioxidant and anti-inflammatory property. Abbreviation used: AD: Alzheimer's disease, ANOVA: Analysis of Variance, aCSF: Artificial cerebrospinal fluid, CAPE: Caffeic acid phenethylester, EPM: Elevated plus maze, ELT: Escape latency time, GSH: Reduced glutathione, IL: Interleukin, ICV: Intracerebroventricular, MDA: Malondialdehyde, MEL: Mean escape latency, MWM: Morris water maze, NFTs: Neurofibrillary tangles, RNS: Reactive nitrogen species, ROS: Reactive oxygen species, SEM: Standard error of mean, STZ: Streptozotocin, TBARS: Thiobarbituric reactive substances, TSTQ: Time spent in target quadrant, TL: Transfer latency, TNF-α: Tumor necrosis factor alpha.