Structure-based virtual screening of plant-derived natural compounds as potential PPARα agonists for the treatment of dyslipidemia

  • Phuong Thuy Viet Nguyen
  • Truong Le Quang Vo
  • Thao Anh Nguyen
  • Phuong Ngoc Khanh Ho
  • Bao Hoang Gia Nguyen
Keywords: structure-based virtual screening, molecular docking, PPARα, natural compounds, dyslipidemia


Background: Nowadays, metabolic disorders such as dyslipidemia have become serious health problems in the modern world. PPARs are regulators of numberous metabolic pathways, hence there has been a huge increase in the development and use of the PPARs agonists, especially PPARα agonists as main therapeutic of dyslipidemia.

Objectives: The study aimed to explore potential plant-derived natural compounds as PPARα agonist agent for drug discovery of dyslipidemia. Methods: Structure-based virtual screening through molecular docking was conducted for 142 bioactive compounds from 29 medicinal plants on the main binding site of PPARα (PDB ID: 5HYK). Binding affinities and binding interactions between the ligands and PPARα were investigated.

Results: Screening results showed that 34 compounds had strong binding affinities into the PPARα (binding affinities of less than -8.0 kcal.mol-1), including 20 flavonoid, 4 terpenoid and 10 alkaloid compounds. Flavonoid was found as the best group which fitted well in the binding site of the PPARα. Top compounds were identified, including formononetin from Thermopsis alterniflora (-10.2 kcal.mol-1), diosmetin from Musa spp. (-10.1 kcal.mol-1), luteolin from Elsholtzia ciliate (-9.9 kcal.mol-1); steviol from Stevia rebaudiana (-9.4 kcal.mol-1); and tuberocrooline from Stemona tuberosa (-10.5 kcal.mol-1), respectively. These compounds showed the potential agonistic activities due to forming the hydrogen bonds as well as hydrophobic interactions with four key residues of the receptor such as Ser280, Tyr314, His440 and Tyr464.

Conclusions: These potential natural compounds may provide useful information in the drug design and discovery for anti-dyslipidemia agents.

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