Lobetyolin, an anti-AD factor from the diet campanulaceae source, metabolism regulation and target exploration

IF 4.9 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2025-09-12 DOI:10.1007/s13659-025-00549-0

Wen Huang, Yihan Liu, Haixin Jiang, Dongxue Guo, Yi Song, Junqi Wang, Luqi Li, Qiang Zhang

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引用次数: 0

Abstract

Bioactive compounds from food-compatible medicinal herbs have shown promise as preventive agents against age-related neurodegenerative conditions, particularly Alzheimer’s disease (AD). The present work aimed to find Lobetyolin as a new suppressor of Aβ aggregation and its interventions on abnormal metabolism in AD. Aβ-expressing Caenorhabditis elegans (strain CL4176) and wild-type worms were employed to evaluate paralysis onset, lifespan, cerebral Aβ deposition, and intracellular reactive oxygen species (ROS) after Lobetyolin administration. Untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) metabolomics coupled with RNA-seq transcriptomics was carried out to profile systemic metabolic and gene-expression changes. Differential metabolites and transcripts were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and pathway-impact analyses; hub targets were prioritized by integrating enrichment scores with in-silico docking. Lobetyolin (12.5–50 µM) markedly protected C. elegans from Aβ-driven toxicity and oxidative stress. In CL2006 worms, β-amyloid deposits fell by 54.8 ± 9.4%, while paralysis in CL4176 was delayed by 20.9 ± 4.5%. Lifespan increased by up to 18.2% in CL4176 and 25.0% in wild-type N2 worms. Concomitantly, intracellular ROS declined maximally by 28.1 ± 8.9% (N2) and 22.4 ± 3.8% (CL4176). Integrative metabolomic–transcriptomic analyses, validated by RT-qPCR, revealed selective remodeling of glutathione metabolism: gst-38 expression was suppressed, whereas gst-1 was elevated. Lobetyolin confers neuroprotective and geroprotective benefits in vivo, primarily through reprogramming glutathione-centered redox metabolism and selectively modulating glutathione-S-transferases (GST) isoforms. These findings position Lobetyolin as a promising dietary lead compound for AD prevention and healthy aging interventions.

Graphical Abstract

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芦贝苷，一种抗ad的饮食因子，从藤科来源、代谢调控及靶点探索

从食物相容的草药中提取的生物活性化合物已经显示出作为预防与年龄相关的神经退行性疾病，特别是阿尔茨海默病（AD）的前景。本研究旨在寻找一种新的a β聚集抑制因子及其对AD异常代谢的干预作用。以表达Aβ的秀丽隐杆线虫（CL4176）和野生型线虫为研究对象，观察给毒后麻痹发作、寿命、脑内Aβ沉积和细胞内活性氧（ROS）的变化。非靶向超高效液相色谱-高分辨率质谱（UHPLC-HRMS）代谢组学结合RNA-seq转录组学分析了全身代谢和基因表达的变化。对差异代谢物和转录本进行京都基因和基因组百科全书（KEGG）、基因本体（GO）和途径影响分析；通过将富集分数与计算机对接相结合，对中枢目标进行优先排序。12.5 ~ 50µM的Lobetyolin可显著保护秀丽隐杆线虫免受a β驱动的毒性和氧化应激。CL2006虫的β-淀粉样蛋白沉积减少了54.8±9.4%，而CL4176虫的麻痹延迟了20.9±4.5%。CL4176虫的寿命增加18.2%，野生型N2虫的寿命增加25.0%。同时，细胞内ROS下降幅度最大，分别为28.1±8.9% （N2）和22.4±3.8% （CL4176）。通过RT-qPCR验证的综合代谢组学-转录组学分析揭示了谷胱甘肽代谢的选择性重塑：gst-38表达被抑制，而gst-1表达升高。Lobetyolin在体内主要通过重编程谷胱甘肽为中心的氧化还原代谢和选择性调节谷胱甘肽s -转移酶（GST）异构体，赋予神经保护和老年保护作用。这些发现表明，罗贝多林是一种很有前景的饮食先导化合物，可用于预防阿尔茨海默病和健康衰老干预。图形抽象

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来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.