Mulberry Diels-Alder-type adducts (MDAAs) are a group of structurally unique natural products biosynthetically derived from the intermolecular [4 + 2] cycloaddition of a dehydroprenylphenol and a chalcone. In the current study, ten MDAAs, including an undescribed one, inethermulberrofuran C, were isolated from the root bark of Morus alba. The anti-Alzheimer's disease (anti-AD) properties of these isolates were systematically screened for a series of potential targets (Aβ self-aggregation, tau aggregation, and ChEs) as well as the anti-neuroinflammatory and neuroprotective activities. Four compounds, mulberrofuran C, mulberrofuran K, mulberrofuran G, and isomulberrofuran G, turned out to be potent multi-targeted agents for AD. Among them, mulberrofuran K with a good blood-brain barrier (BBB) permeability (8.7 ± 0.3 × 10-6 cm/s) was selected as a promising candidate for further mechanism study in glutamate-induced HT22 cell model, which showed its neuroprotective ability on up-regulation of the glutathione (GSH) level and suppression of the reactive oxygen species (ROS) production.

中文翻译：

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桑椹桤木型加合物作为阿尔茨海默病的多靶点药物

Mulberry Diels-Alder 型加合物 (MDAAs) 是一组结构独特的天然产物，由脱氢异戊二烯基苯酚和查耳酮的分子间 [4 + 2] 环加成生物合成衍生而来。在目前的研究中，从桑树的根皮中分离出 10 种 MDAA，包括一种未描述的 MDAA，inethermulberrofuran C。系统地筛选了这些分离株的抗阿尔茨海默病 (anti-AD) 特性，以寻找一系列潜在目标（Aβ 自聚集、tau 聚集和 ChE）以及抗神经炎症和神经保护活性。四种化合物，桑葚C、呋喃K、呋喃G和异桑呋喃G，被证明是有效的AD多靶向药物。其中，桑葚K具有良好的血脑屏障（BBB）通透性（8.7±0.