Abstract
More and more evidences show that pectin polysaccharide may have impact on Aβ42, one important molecule implicated in Alzhemer's disease pathology. We speculate special structural motif of pectin might have better bioactivity on Aβ42. To address this hypothesis, we reported structure and impact of a novel pectin RP02-1 with the molecular weight of 116.0 kDa from roots of Polygala tenuifolia on Aβ42 aggregation and production and the underlying mechanism. Its structure is characterized as a backbone of alternate 1, 2, 4-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 3-,1, 4-, 1, 6- and 1, 3, 6-linked β-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity study shows that this pectin may significantly block the aggregation of Aβ42. We further show that RP02-1 suppresses Aβ42 production with no apparent cytotoxicity in both CHO/APPBACE1 and HEK293-APPsw cells. Mechanism study demonstrates that RP02-1 may enhance the expression of insulin-degradation enzyme (IDE) and neprilysin (NEP), which are the main enzymes involved in Aβ degradation. These results suggest that RP02-1 may be a candidate leading compound for anti-Alzheimer's disease new drug development by attenuating Aβ42 production and inhibiting Aβ42 aggregation.