Taxifolin targets HMGCR, LDLR and APOB to ameliorate hyperlipidemia: insights from systems pharmacology and nanoemulsion-based delivery
6 affiliations
- 1Department of Pharmacognosy, College of Pharmacy, King Saud University, 11451Riyadh, Saudi Arabia
- 2Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
- 3Center for Research on Medicinal, Aromatic, and Poisonous Plants, DSR, King Saud University, P.O. Box 2457, Riyadh, Saudi Arabia
- 4Department of Pharmacognosy, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya
- 5College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan, 450001, China
- 6Department of Chemistry, Thomas J. R. Faulkner College of Science and Technology, University of Liberia, Monrovia, Montserrado County, Liberia
Abstract
Hyperlipidemia is a major risk factor for cardiovascular disease, highlighting the need for safer and effective therapeutic options. This study evaluated the anti-hyperlipidemic potential of taxifolin (TXF) and its nanoemulsion formulation (TXF-NE) using integrated computational and experimental approaches. Network pharmacology identified 177 common targets between TXF and hyperlipidemia, with enrichment analyses linking these targets to lipid metabolism, cholesterol regulation, and inflammatory pathways. Protein-protein interaction analysis revealed key lipid-regulating genes, including HMGCR as a major hub target. Molecular docking predicted favorable interactions of TXF with several lipid metabolism related proteins, including HMGCR, LDLR, APOB, APOA1, and ACSM2A. The predicted interactions provide structural hypotheses regarding potential TXF protein associations. In-vivo, TXF significantly improved serum lipid profiles and liver function enzymes. Gene expression and protein analyses exhibited downregulation of HMGCR and APOB along with upregulation of LDLR, indicating suppression of cholesterol synthesis, reduced lipoprotein production, and enhanced LDL clearance. Notably, TXF-NE exhibited high drug content and better therapeutic efficacy relative to free TXF, as reflected by greater improvements in lipid parameters. Overall, these findings demonstrate that TXF alleviates hyperlipidemia through a multi-target mechanism, while nanoemulsion-based delivery enhances its therapeutic potential for managing hyperlipidemia and associated hepatic dysfunction.
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BibTeX
@article{abdullah2026taxifolin,
title = {{Taxifolin targets HMGCR, LDLR and APOB to ameliorate hyperlipidemia: insights from systems pharmacology and nanoemulsion-based delivery}},
author = {Alanzi Abdullah R. and Fatima Iman and Ashraf Muhammad Umer and Malik Muhammad Nasir Hayat and Herqash Rashed N. and Abugrain Mostafa E. and Atif Muhammad and Abbas Munawar and Solre Gideon F.B.},
journal = {Open Life Sciences},
year = {2026},
month = oct,
doi = {10.1515/biol-2025-1392},
url = {https://doi.org/10.1515/biol-2025-1392},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Taxifolin targets HMGCR, LDLR and APOB to ameliorate hyperlipidemia: insights from systems pharmacology and nanoemulsion-based delivery
AU - Alanzi Abdullah R.
AU - Fatima Iman
AU - Ashraf Muhammad Umer
AU - Malik Muhammad Nasir Hayat
AU - Herqash Rashed N.
AU - Abugrain Mostafa E.
AU - Atif Muhammad
AU - Abbas Munawar
AU - Solre Gideon F.B.
PY - 2026
DA - 2026/10/26
JO - Open Life Sciences
DO - 10.1515/biol-2025-1392
UR - https://doi.org/10.1515/biol-2025-1392
AB - Hyperlipidemia is a major risk factor for cardiovascular disease, highlighting the need for safer and effective therapeutic options. This study evaluated the anti-hyperlipidemic potential of taxifolin (TXF) and its nanoemulsion formulation (TXF-NE) using integrated computational and experimental approaches. Network pharmacology identified 177 common targets between TXF and hyperlipidemia, with enrichment analyses linking these targets to lipid metabolism, cholesterol regulation, and inflammatory pathways. Protein-protein interaction analysis revealed key lipid-regulating genes, including HMGCR as a major hub target. Molecular docking predicted favorable interactions of TXF with several lipid metabolism related proteins, including HMGCR, LDLR, APOB, APOA1, and ACSM2A. The predicted interactions provide structural hypotheses regarding potential TXF protein associations. In-vivo, TXF significantly improved serum lipid profiles and liver function enzymes. Gene expression and protein analyses exhibited downregulation of HMGCR and APOB along with upregulation of LDLR, indicating suppression of cholesterol synthesis, reduced lipoprotein production, and enhanced LDL clearance. Notably, TXF-NE exhibited high drug content and better therapeutic efficacy relative to free TXF, as reflected by greater improvements in lipid parameters. Overall, these findings demonstrate that TXF alleviates hyperlipidemia through a multi-target mechanism, while nanoemulsion-based delivery enhances its therapeutic potential for managing hyperlipidemia and associated hepatic dysfunction.
SN - 2391-5412
ER -