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Identification of lignans as ATP citrate lyase (ACLY) inhibitors from the roots of . | LitMetric

AI Article Synopsis

  • A new lignan called pouzolignan P was discovered along with 14 other known lignans from the roots of a specific plant, and their structures were identified through detailed spectroscopy.
  • Four lignans were found to have strong inhibitory effects on ATP citrate lyase (ACLY), which is important for cholesterol metabolism, with IC values indicating their effectiveness.
  • Further studies showed that one of these compounds significantly reduced total cholesterol levels in liver cells, and molecular docking revealed it interacted strongly with a key site on the ACLY enzyme.

Article Abstract

A new lignan, named pouzolignan P (), together with 14 known ones () were isolated from the roots of (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 (), gnemontanins E (), gnetuhainin I (), and styraxlignolide D () showed excellent ACLY inhibitory effect with IC 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 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 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.

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Source
http://dx.doi.org/10.1080/14786419.2023.2219816DOI Listing

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