Aging is characterized by chronic inflammation, oxidative stress and progressive cellular senescence. Thymoquinone (TQ), a major bioactive constituent of Nigella sativa oil, has attracted considerable research interest due to its anti-inflammatory and anti-oxidative properties. However, its integrated effects using widely used aging markers i.e. senescence associated beta-galactosidase (SA-β-gal) and lipofuscin granules, in D-galactose (D-gal) induced premature aging models has not been addressed yet. This study investigates the potential of TQ in attenuating D-gal induced premature aging and its associated phenotypes through its anti-inflammatory and anti-oxidative properties in a mouse model. Male Swiss Webster albino mice were divided into five groups: control, D-gal (600 mg/kg) to induce premature aging and three TQ treatment groups (5, 10 and 20 mg/kg) with D-gal for eight weeks. SA-β-gal activity and lipofuscin accumulation were estimated for aging, IL-6, IL-8, E-selectin, ICAM-1 as inflammatory mediators, malondialdehyde (MDA) and total antioxidant capacity (TAC) for oxidative stress, while total nitric oxide metabolites (NOx) to evaluate nitric oxide bioavailability. D-gal induced premature aging was evidenced by increased SA-β-gal expression and lipofuscin granules accumulation in liver and kidney tissues. TQ significantly attenuated these alterations by down regulating IL-6, IL-8, E-selectin and ICAM-1, restoring anti-oxidant balance by decreasing MDA, restoring TAC and NOx with TQ 20 mg/kg showing the strongest effect. Using SA-β-gal and lipofuscin as widely used aging markers, our findings provide compelling evidence in vivo that TQ exhibit anti-aging effects by modulating inflammation, restoring NOx balance and curbing oxidative stress, highlighting its potential as therapeutic agent for age-related diseases.
