A flavonoid-based approach to mitigating hyperglycaemia: in silico analysis of AMPK activation, membrane and metabolic effects of rutin in hepg2 cells
| dc.contributor.author | Odugbemi, Adeshina Isaiah | |
| dc.contributor.author | Tata, Fave Yohanna | |
| dc.contributor.author | Ugbaja, Samuel Chima | |
| dc.date.accessioned | 2026-01-16T07:26:05Z | |
| dc.date.available | 2026-01-16T07:26:05Z | |
| dc.date.issued | 2025 | |
| dc.description.abstract | Hyperglycaemia exacerbates tissue damage and complications in COVID-19 and metabolic disorders. Flavonoids have shown diverse therapeutic potential in metabolic and infectious diseases, yet their molecular mechanisms remain unclear. The 5' adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor and a promising therapeutic target in diabetes and viral infections. This study investigated the binding affinity, structural stability and conformational dynamics of flavonoids with AMPK through molecular docking, molecular dynamics (MD) simulations (Maestro Schrodinger, Amber 18) carried out for 100 ns, and MM/GBSA binding free energy calculations. In vitro cytotoxicity and biochemical assays, including MTT, ATP, ΔΨm, CYP3A4, and LDH, were performed on HepG2 cells and analyzed using one-way ANOVA with Tukey's post hoc test. Rutin showed the strongest binding to AMPK (−64.87 ± 10.07 kcal/mol), indicating superior binding and potential biological effects. Computational analysis identified key residues Glu86, Glu92, Glu135 and Asp149 involved in direct hydrogen bonding and electrostatic interactions, contributing to binding affinity and stability in the AMPK binding pocket. Rutin maintained nearly 100% cell viability up to 500 µM, significantly increased ATP and CYP3A4 levels while reducing LDH without impacting ΔΨm, indicating preserved mitochondrial integrity, enhanced metabolism and bioenergetics. These findings showed rutin as a safe and potent AMPK modulator with potential for further optimization and preclinical evaluations to treat diabetes and other diseases associated with mitochondrial dysfunction and metabolic stress. | |
| dc.identifier.citation | Tata, F.Y., Ugbaja, S.C., Nxumalo, M.B., Odugbemi, A.I., Kumalo, H.M. and Khan, R., 2025. A Flavonoid‐Based Approach to Mitigating Hyperglycaemia: In Silico Analysis of AMPK Activation, Membrane and Metabolic Effects of Rutin in HepG2 Cells. ChemistrySelect, 10(36), p.e01432. | |
| dc.identifier.uri | https://doi.org/10.1002/slct.202501432 | |
| dc.identifier.uri | https://hdl.handle.net/10566/21734 | |
| dc.language.iso | en | |
| dc.publisher | John Wiley and Sons Inc | |
| dc.subject | AMPK | |
| dc.subject | Diabetes | |
| dc.subject | Flavonoids | |
| dc.subject | Molecular dynamics simulations | |
| dc.subject | Rutin | |
| dc.title | A flavonoid-based approach to mitigating hyperglycaemia: in silico analysis of AMPK activation, membrane and metabolic effects of rutin in hepg2 cells | |
| dc.type | Article |