Identification of flavonoids from natural products against hyperlipidaemia through computational approaches.

Authors

Nurnazira Hanis Mustaffar Kamal, Nurul Azira Ismail, Ernie Zuraida Ali

Published in

PloS one. Volume 21. Issue 10. Pages e0346073. Epub Oct 09, 2026.

Abstract

Over the centuries, hyperlipidaemia has been recognised as a major risk factor contributing to cardiovascular disease (CVD). Current research increasingly explores natural compounds such as flavonoids for their potential lipid-lowering effects. This study evaluated pharmacological potential of flavonoids to identify strong inhibitors for target receptor, Proprotein Convertase Subtilisin/Kexin Type (PCSK9). A total of 29 compounds, including one FDA-approved drugs were screened for drug-likeness and ADMET properties, followed by molecular docking and Molecular Dynamics (MD) simulations using PCSK9 receptor containing glucose and sodium (PDB ID: 5OCA). This complex was chosen due to their functional relevance to cholesterol metabolism. As a results, 24 compounds satisfied Lipinski's Rule of Five and exhibited favourable drug-likeness and toxicity profiles. Simvastatin (control) was discovered to bind into the pocket B binding site along with seven flavonoids; Diosmetin, Eupatorin, Isorhamnetin, Myricetin, Petunidin, Sinensetin, and Tilianin. These flavonoids displayed docking energies ranging from -8.0 to -10.2 kcal/mol. Tilianin showed the strongest affinity (-10.2 kcal/mol), while Simvastatin bound with -9.1 kcal/mol. MD simulations confirmed that the PCSK9-ligand complexes remained structurally stable throughout a 100 ns trajectory. MM/PBSA analysis further supported the binding interactions, revealing free energies values ranging from -17 to -30.41 kcal/mol. Among the flavonoids evaluated, Tilianin, Myricetin, and Sinensetin demonstrate the most favourable interaction profiles. These finding suggest that the selected flavonoids have strong potential as promising anti-hyperlipidaemic candidates targeting PCSK9.

PMID:
42853886
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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