Sarsasapogenin-AA13 ameliorates Aβ-induced cognitive deficits via improving neuroglial capacity on Aβ clearance and antiinflammation.

Abstract

AIMS:

Sarsasapogenin has been reported to improve dementia symptoms somehow, probably through modulating the function of cholinergic system, suppressing neurofibrillary tangles, and inhibiting inflammation. However, the role of sarsasapogenin in response to beta-amyloid (Aβ) remains to be delineated. This study aimed to determine the therapeutic effect of sarsasapogenin-13 (AA13, a sarsasapogenin derivative) on learning and memory impairments in Aβ-injected mice, as well as the role of AA13 in neuroglia-mediated antiinflammation and Aβ clearance.

METHODS:

Focusing on the role of AA13 in regulating glial responses to Aβ, we conducted behavioral, morphological, and protein expression studies to explore the effects of AA13 on Aβ clearance and inflammatory regulation.

RESULTS:

The results indicated that oral administration of AA13 attenuated the memory deficits of intracerebroventricular (i.c.v.) Aβ-injected mice; also, AA13 protected neuroglial cells against Aβ-induced cytotoxicity. The further mechanical studies demonstrated that AA13 reversed the upregulation of proinflammatory M1 markers and increased the expression of antiinflammatory M2 markers in Aβ-treated cells. Furthermore, AA13 facilitated Aβ clearance through promoting Aβ phagocytosis and degradation. AA13 modulated the expression of fatty acid translocase (CD36), insulin-degrading enzyme (IDE), neprilysin (NEP), and endothelin-converting enzyme (ECE) in neuroglia.

CONCLUSION:

The present study indicated that the neuroprotective effect of AA13 might relate to its modulatory effects on microglia activation state, phagocytic ability, and expression of Aβ-degrading enzymes, which makes it a promising therapeutic agent in the early stage of Alzheimer's disease (AD).

• Authors: Cui Huang, Dong Dong, Qian Jiao, Hui Pan, Lei Ma, Rui Wang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 23 Issue 6 Pg. 498-509 (Jun 2017) ISSN: 1755-5949 [Electronic] England
• PMID: 28466999 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• Spirostans
• amyloid beta-protein (1-42)
• sarsasapogenin

Topics

• Amyloid beta-Peptides (toxicity)
• Analysis of Variance
• Animals
• Animals, Newborn
• Cells, Cultured
• Cerebral Cortex (cytology)
• Cognition Disorders (chemically induced, drug therapy)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Injections, Intraventricular
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Inbred ICR
• Neuroglia (drug effects, physiology)
• Peptide Fragments (toxicity)
• Phagocytosis (drug effects)
• Spirostans (chemistry, therapeutic use)
• Time Factors