2. Academic Validation
  3. Identification of lignans as ATP citrate lyase (ACLY) inhibitors from the roots of Pouzolzia zeylanica

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

  • Nat Prod Res. 2023 Jun 2:1-8. doi: 10.1080/14786419.2023.2219816.
Jin-Long Li 1 2,  Jia-Yi Jiang 1,  Shan-Shan Gu 3,  Lei Zhang 1,  Yan Sun 3 4,  Xue-Han Wang 2,  Dan-Yu Li 2,  Zhe-Yu Chen 1,  Sheng-Shi Jiang 3,  Wei-Zhong Zhu 1,  Hao-Wen Jiang 4 5,  Hong-Jie Zhang 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Nantong University, Nantong, People's Republic of China.
  • 2 School of Chinese Medicine, Hong Kong Baptist University, Kowloon, People's Republic of China.
  • 3 Department of Pharmacy, Nantong Hospital of Traditional Chinese Medicine, Nantong, People's Republic of China.
  • 4 Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, People's Republic of China.
  • 5 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
PMID: 37265118 DOI: 10.1080/14786419.2023.2219816
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.

Keywords

ATP citrate lyase (ACLY) inhibitors; Pouzolzia zeylanica; lignans.

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