Gentidelasides A−G: Loganin derivatives from Gentiana delavayi with reducing Aβ secretion via suppressing BACE1 expression

IF 3.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Phytochemistry Pub Date : 2024-11-14 DOI:10.1016/j.phytochem.2024.114333
Hai-Hui Guo , Chun-Xu Li , Min Yang , Feng-Feng Li , Hui-Yun Yang , Ming Yin , Jia-Peng Wang , Fu-Sheng Wang
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Abstract

Gentidelasides A−G (17) seven unreported loganin derivatives and fourteen known compounds (821) 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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Gentidelasides A-G:来自 Gentiana delavayi 的 loganin 衍生物,可通过抑制 BACE1 的表达减少 Aβ 的分泌。
从 Gentiana delavayi Franch 的花中分离出了 Gentidelasides A-G(1-7)、7 种未曾报道过的 loganin 衍生物和 14 种已知化合物(8-21)。通过大量的核磁共振光谱、电离辐射光谱和 HRESIMS 分析以及酶水解,这些化合物的结构(包括绝对构型)得到了明确的阐释。在体外生物测定中,化合物7对Aβ40和Aβ42的产生有明显的抑制作用,IC50值分别为0.052±0.0023 nM和1.52±0.95 nM,可能是通过抑制β位淀粉样前体蛋白裂解酶1的表达而起到预防阿尔茨海默病的作用。分子对接模拟显示,化合物 7 通过活性位点空腔中的亲水和疏水相互作用抑制了 BACE1。
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来源期刊
Phytochemistry
Phytochemistry 生物-植物科学
CiteScore
6.40
自引率
7.90%
发文量
443
审稿时长
39 days
期刊介绍: Phytochemistry is a leading international journal publishing studies of plant chemistry, biochemistry, molecular biology and genetics, structure and bioactivities of phytochemicals, including ''-omics'' and bioinformatics/computational biology approaches. Phytochemistry is a primary source for papers dealing with phytochemicals, especially reports concerning their biosynthesis, regulation, and biological properties both in planta and as bioactive principles. Articles are published online as soon as possible as Articles-in-Press and in 12 volumes per year. Occasional topic-focussed special issues are published composed of papers from invited authors.
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