A novel pectin from Polygala tenuifolia blocks Aβ aggregation and production by enhancing insulin-degradation enzyme and neprilysin.

More and more evidences show that pectin polysaccharide may have impact on Aβ one important molecule implicated in Alzhemer's disease pathology. We speculate special structural motif of pectin might have better bioactivity on Aβ. 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 Aβ 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 Aβ. We further show that RP02-1 suppresses Aβ 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 Aβ production and inhibiting Aβ aggregation.