Sarsasapogenin‐ AA 13 ameliorates A β ‐induced cognitive deficits via improving neuroglial capacity on A β clearance and antiinflammation

Summary 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 (A β ) remains to be delineated. This study aimed to determine the therapeutic effect of sarsasapogenin‐13 ( AA 13, a sarsasapogenin derivative) on learning and memory impairments in A β ‐injected mice, as well as the role of AA 13 in neuroglia‐mediated antiinflammation and A β clearance. Methods Focusing on the role of AA 13 in regulating glial responses to A β , we conducted behavioral, morphological, and protein expression studies to explore the effects of AA 13 on A β clearance and inflammatory regulation. Results The results indicated that oral administration of AA 13 attenuated the memory deficits of intracerebroventricular (i.c.v.) A β ‐injected mice; also, AA 13 protected neuroglial cells against A β ‐induced cytotoxicity. The further mechanical studies demonstrated that AA 13 reversed the upregulation of proinflammatory M1 markers and increased the expression of antiinflammatory M2 markers in A β ‐treated cells. Furthermore, AA 13 facilitated A β clearance through promoting A β phagocytosis and degradation. AA 13 modulated the expression of fatty acid translocase ( CD 36), insulin‐degrading enzyme ( IDE ), neprilysin ( NEP ), and endothelin‐converting enzyme ( ECE ) in neuroglia. Conclusion The present study indicated that the neuroprotective effect of AA 13 might relate to its modulatory effects on microglia activation state, phagocytic ability, and expression of A β ‐degrading enzymes, which makes it a promising therapeutic agent in the early stage of Alzheimer's disease ( AD ).