Identification of flavonoids from natural products against hyperlipidaemia through computational approaches
- 1School of Graduate Studies, Postgraduate Centre Management and Science University, University Drive, Shah Alam, Selangor, Malaysia
- 2Faculty of Health and Life Sciences, Management and Science University, University Drive, Shah Alam, Selangor, Malaysia
- 3Institute for Medical Research, National Institutes of Health Malaysia, Shah Alam, Selangor, Malaysia
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.
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BibTeX
@article{kamal2026identification,
title = {{Identification of flavonoids from natural products against hyperlipidaemia through computational approaches}},
author = {Nurnazira Hanis Mustaffar Kamal and Nurul Azira Ismail and Ernie Zuraida Ali},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0346073},
url = {https://doi.org/10.1371/journal.pone.0346073},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Identification of flavonoids from natural products against hyperlipidaemia through computational approaches
AU - Nurnazira Hanis Mustaffar Kamal
AU - Nurul Azira Ismail
AU - Ernie Zuraida Ali
PY - 2026
DA - 2026/10/09
JO - PLOS One
DO - 10.1371/journal.pone.0346073
UR - https://doi.org/10.1371/journal.pone.0346073
AB - 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.
SN - 1932-6203
ER -