Spiro-Polycyclic Polyprenylated Acylphloroglucinols from Hypericum monogynum and Their anti-Alzheimer’s Disease Effects

IF 3.7 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2026-09-25 Epub Date: 2026-08-12 DOI:10.1021/acs.jnatprod.6c00583

Wenjing Tian, Shoulun He, Tingjiya Wang, Shengfei Zhong, Jingyu Sun, Junjie Chen, Xiaoyi Wang, Chunchun Du, Yuhang You, Yingting Lin, Ye Wang, Guanghui Wang, Xiaobin Li, Haifeng Chen

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引用次数: 0

Abstract

Eight undescribed spiro-polycyclic polyprenylated acylphloroglucinols (PPAPs) with a 6/6/5 tricyclic architecture (1−8), together with eight known analogues (9−16), were isolated from Hypericum monogynum L. Their structures including absolute configurations were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Biological evaluation revealed that compounds 4 and 16 showed potential as dual-target anti-Alzheimer’s disease (AD) lead compounds, as they not only exhibited potent acetylcholinesterase (AChE) inhibitory activities but also induced peroxisome proliferator-activated receptor-γ transactivation and upregulated ATP-binding cassette transporter A1 expression. The in vivo anti-AD effects of 4 and 16 were evaluated by the zebrafish behavioral experiments. Compound 16 exhibited anti-AD effects with no detectable toxicity or teratogenicity, whereas 4 exhibited toxicity to zebrafish at 10 μM. These findings not only expand the chemical diversity of spiro-PPAPs but also underscore their potential as dual-target agents for AD treatment.

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金丝桃中多环聚戊烯酰化酰基间苯三酚及其抗阿尔茨海默病作用

从金丝桃（Hypericum monogynum L.）中分离到8个未描述的6/6/5三环结构的螺旋多环聚丙烯酰化酰基间苯三醇（PPAPs）（1−8），以及8个已知的类似物（9−16），通过光谱分析、单晶x射线衍射和量子化学计算对其结构进行了鉴定。生物学评价表明，化合物4和16不仅表现出有效的乙酰胆碱酯酶（AChE）抑制活性，而且还能诱导过氧化物酶体增殖体激活受体-γ反激活和上调atp结合盒转运体A1的表达，因此具有作为抗阿尔茨海默病（AD）双靶点先导化合物的潜力。通过斑马鱼行为实验评价了4和16的体内抗ad作用。化合物16表现出抗ad的作用，但没有检测到毒性或致畸性，而化合物4在10 μM下对斑马鱼表现出毒性。这些发现不仅扩大了螺- ppaps的化学多样性，而且强调了它们作为阿尔茨海默病治疗双靶点药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.