<i>Ocimum Gratissimum</i> L. Leaves Extract Protects Osteoblast‐Like Cells From Glucose‐Induced Stress by Antioxidant Mechanisms and RUNX2 Signaling: A Combined Experimental and Computational Study

ABSTRACT Secondary osteoporosis due to diabetes is a metabolic bone disorder where hyperglycemia impairs bone formation by suppressing osteoblast activity. Ocimum gratissimum L. has long been used in ethnomedicine and pharmacology for various illnesses. This study examines the osteogenic potential of Ocimum gratissimum leaf extract using both in vitro and in silico analysis. GC–MS analysis of OGLE confirmed the presence of flavonoids, polyphenols, terpenoids, sesquiterpenes, etc, and exhibited antioxidant potential (49.8 µg/mL). High glucose causes cytotoxic effects in MG‐63 cells with an IC 50 of approximately 45 mM. OGLE improved cell proliferation (p &lt; 0.0001) , restored alkaline phosphatase activity (p &lt; 0.05) , and significantly enhanced matrix mineralization (p &lt; 0.0001) under hyperglycemic conditions. Molecular docking was performed using AutoDock 4.2 to assess their binding interactions with osteogenic targets RUNX2 and osteocalcin, followed by in silico evaluation of their physicochemical properties, pharmacokinetics, lipophilicity, and drug‐likeness properties using PubChem and SwissADME. In silico analysis demonstrated favorable binding of γ‐tocopherol, copaene, and caryophyllene with RUNX2 (binding energies −5.4, −5.2, and −4.9 kcal/mol, respectively) and OCN (−4.7, −5.6, and −6.0 kcal/mol, respectively). Collectively, these results indicate that OGLE may mitigate high‐glucose‐induced osteoblast dysfunction through its antioxidant properties and modulation of osteogenic proteins, highlighting its potential as an anti‐osteoporotic agent.