Identification of lignans as ATP citrate lyase (ACLY) inhibitors from the roots of Pouzolzia zeylanica

Jin-Long Li*, Jia-Yi Jiang, Shan-Shan Gu, Lei Zhang, Yan Sun, Xue-Han Wang, Dan-Yu Li, Zhe-Yu Chen, Sheng-Shi Jiang, Wei-Zhong Zhu, Hao-Wen Jiang*, Hong-Jie Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

A new lignan, named pouzolignan P (1), together with 14 known ones (2 − 15) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K (3), gnemontanins E (5), gnetuhainin I (6), and styraxlignolide D (15) showed excellent ACLY inhibitory effect with IC50 values of 9.06, 0.59, 2.63, and 7.62 μM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.

Original languageEnglish
JournalNatural Product Research
DOIs
Publication statusE-pub ahead of print - 2 Jun 2023

Scopus Subject Areas

  • Analytical Chemistry
  • Biochemistry
  • Plant Science
  • Organic Chemistry

User-Defined Keywords

  • Pouzolzia zeylanica
  • lignans
  • ATP citrate lyase (ACLY) inhibitors

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