Abstract
The accumulation of amyloid β (Aβ) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aβ clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycan on Aβ42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aβ42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPβ. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aβ42 phagocytosis.