Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat

Abstract

Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a cholesterol-enriched diet and ageing.

Increased Levels of 27‐Hydroxycholesterol Induced by Dietary Cholesterol in Brain Contribute to Learning and Memory Impairment in Rats

“…Accumulating epidemiological and experimental studies have confirmed that high‐CDs have affected the cognitive performance in animal models . In the present study, we found that CD feeding for 4 weeks has no effect on the body weight and organ coefficient of rats, which are consistent with the results of Li and Ya .…”

Himalayan Nettle Girardinia diversifolia as a Candidate Ingredient for Pharmaceutical and Nutraceutical Applications—Phytochemical Analysis and In Vitro Bioassays

“…In particular, the results obtained in the chemical bioassays showed significant inhibition of cholinesterase. A previous paper indicated that phytosterols can have inhibitory properties on AChE and BuChE [24,29,37,38] and phytol has also been studied in this regard [24]. Previous published literature showed that phenolic constituents can act as inhibitors of these enzymes [39], thus suggesting that multiple compounds in the phytocomplex of G. diversifolia may be the responsible for the observed activity.…”

“…The presence of phytosterols, phytol and syringin make the extract of G. diversifolia a promising ingredient for nutraceuticals targeted for neuroprotection. Considering the lipophilic portion, a recent paper demonstrated an efficient neuroprotective role of phytosterols against high-cholesterol diet-induced cognitive deficits in aged rats [29].…”

The Antioxidant and Anti-Aging Effects of Acetylated Mycelia Polysaccharides from Pleurotus djamor

“…Acetylcholinesterase has the strongest effect on the physiological concentration of acetyl choline (Ach) and higher specificity. The aging condition can be improved by restoring the content of acetylcholine in the cerebral cortex and reducing the activity of acetylcholinesterase [38]. Aging can lead to diabetes and other diseases.…”