echinacoside and Cognitive-Dysfunction

The current study aimed to examine the effects of echinacoside on cognitive impairment in mice after exposure to sevoflurane. To examine the role of FOXO1, si-FOXO1 and si-con were injected into the hippocampus through the left lateral cerebral ventricles. Sevoflurane-induced mice had serious cognitive dysfunction. However, pretreatment with echinacoside alleviated the cognitive dysfunction, as measured by a shortened escape latency time, and increased platform crossing times, the percentage of distance in the target quadrant and Y-maze spontaneous alternations. In addition, we found that echinacoside elevated FOXO1 expression in the hippocampus; increased the expression of autophagy-related proteins including Beclin 1, ATG5, ATG7, and LC3; and reduced P62 expression. Silencing of FOXO1 aggravated the cognitive deficits and reduced expression of the autophagy-related markers, whereas the effects of si-FOXO1 on memory were abrogated by echinacoside. Echinacoside attenuated the cognitive impairment in sevoflurane-induced mice through FOXO1-mediated autophagy.

Topics: Animals; Autophagy; Cognitive Dysfunction; Forkhead Box Protein O1; Hippocampus; Mice; Sevoflurane

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer's disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Cognitive Dysfunction; Disease Models, Animal; Glycosides; Mice; Mice, Transgenic; Neurodegenerative Diseases; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; PPAR gamma; Presenilin-1; Proto-Oncogene Proteins c-akt; Signal Transduction

To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats.. The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively.. ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01).. ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.

Topics: Acetylcholinesterase; alpha7 Nicotinic Acetylcholine Receptor; Animals; Autophagy; Brain Ischemia; Cerebral Infarction; Cognitive Dysfunction; Glutathione; Glycosides; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke; Superoxide Dismutase