Molecular Docking Studies of Luteolin from Eclipta spp. against Selected Anti-aging Genes

ABSTRACTAging across multiple organ systems is driven by convergent molecular hallmarks including oxidativestress, chronic low-grade inflammation, dysregulated nutrient-sensing signalling, loss of proteostasis,cellular senescence and progressive telomere attrition, processes in which sirtuins (SIRT1, SIRT3), theAMPK-mTOR-FOXO3-IGF1R nutrient-sensing axis, the redox-sensitive transcription factor NRF2, thetumor-suppressor p53, the hormonal regulator Klotho, and the telomerase catalytic subunit TERT arerecognised as central molecular regulators. Ecliptaspp. (E. alba/E. prostrata), traditionally known asBhringraj, is a well-documented Ayurvedic rejuvenator whose principal bioactive flavone, luteolin,possesses notable antioxidant, anti-inflammatory and photoprotective activity. In the present study, an insilico molecular docking approach was employed to evaluate the binding behaviour of luteolin against tenanti-aging-associated protein targets: AMPK1, FOXO3, IGF1R, KLOTHO, MTOR, NRF2, P53, SIRT1,SIRT3 and TERT. Three-dimensional protein structures were retrieved from the RCSB Protein DataBank, prepared using BIOVIA Discovery Studio Visualizer and UCSF ChimeraX, and dockingsimulations were performed in PyRx using AutoDockVina following ligand optimization with OpenBabel. Luteolin showed the most favourable predicted binding affinity towards NRF2 (−9.6 kcal/mol),followed closely by SIRT1 (−9.3 kcal/mol) and MTOR (−9.2 kcal/mol), with consistently favourableaffinities also observed for AMPK1, SIRT3, IGF1R, P53, FOXO3, KLOTHO and TERT (−8.7 to −7.1kcal/mol). The compound satisfied all Lipinski parameters, supporting its oral drug-likeness. Thesecomputational findings rationalise the anti-aging bioactivity reported for Eclipta-derived luteolin in earlierbiochemical studies and support its candidacy as a multi-target natural anti-aging lead compound actingacross nutrient-sensing, oxidative-stress-response, sirtuin, senescence and telomere-maintenancepathways, warranting subsequent in vitro and in vivo validation.