Gentidelasides A-G: Loganin derivatives from Gentiana delavayi with reducing Aβ secretion via suppressing BACE1
Hai-Hui Guo1, Chun-Xu Li1, Min Yang1
1College of Pharmacy, Dali University, Dali, 671000, Yunnan Province, China.
Abstract:
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute configurations were unambiguously elucidated by analysis of extensive NMR spectroscopy, ECD, and HRESIMS, as well as enzymatic hydrolysis. In vitro bioassay, compound 7 showed obvious inhibitory effects on the production of Aβ40 and Aβ42, with IC50 values of 0.052 ± 0.0023 nM and 1.52 ± 0.95 nM, respectively, which probably exert their prevention of Alzheimer's disease by inhibiting the expression of β-site amyloid precursor protein cleaving enzyme 1. The molecular docking simulation revealed that compound 7 inhibited BACE1 through hydrophilic and hydrophobic interactions in the active site cavities.
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