Chemical constituents from the roots of Cynanchum wilfordii with PCSK9 secretion inhibitory activities

IF 3.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Phytochemistry Pub Date : 2024-07-04 DOI:10.1016/j.phytochem.2024.114205

Son Min-Gyung , Pisey Pel , Chae-Yeong An , Chan-Woong Park , Sae Hyun Lee , Tae-Jin Yang , Young-Won Chin

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Abstract

From the Cynanchum wilfordii roots, 32 compounds, including 5 previously undescribed (1, 4-6, 12) and 27 known (2, 3, 7-11, 13-32) compounds, were isolated, and their structures were elucidated using NMR spectroscopic data and MS data aided by ECD calculations or the modified Mosher’s reaction. All isolates were tested for their inhibitory effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion. Among the isolates, compound 4, a methyl cholesterol analog, exhibited the most potent effect in reducing PCSK9 secretion, along with PCSK9 downregulation at the mRNA and protein levels via FOXO1/3 upregulation. Moreover, compound 4 attenuated statin-induced PCSK9 expression and enhanced the uptake of DiI-LDL low-density lipoprotein. Thus, compound 4 is suggested to be a potential candidate for controlling cholesterol levels.

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Cynanchum wilfordii 根部的化学成分具有抑制 PCSK9 分泌的活性。

利用核磁共振光谱数据和质谱数据，并在 ECD 计算或改进的 Mosher 反应的辅助下，阐明了这些化合物的结构。对所有分离物进行了抑制丙蛋白转换酶枯草酶/kexin 9 型（PCSK9）分泌作用的测试。在这些分离物中，化合物 4（一种甲基胆固醇类似物）在减少 PCSK9 分泌方面表现出最有效的作用，同时通过 FOXO1/3 的上调在 mRNA 和蛋白质水平上下调 PCSK9。此外，化合物 4 还能减轻他汀类药物诱导的 PCSK9 表达，并增强 DiI-LDL 低密度脂蛋白的吸收。因此，化合物 4 被认为是控制胆固醇水平的潜在候选化合物。

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

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.