Naringin protects mice from D-galactose-induced lung aging and mitochondrial dysfunction: Implication of SIRT1 pathways.

AIM

Aging is the leading risk factor for diminishing lung function, as well as injury and lung disorder. The target of our research was to examine the potential protective effect of naringin and the possible role of SIRT1 in mice with D-galactose-induced lung aging, by evaluating its effects on antioxidant systems, mitochondrial biogenesis, autophagy, and apoptosis, by referring to the potential involvement of Nrf2/NQO1, LKB1/AMPK/PGC-1α, FOXO1, and P53/caspase-3 signaling.

MATERIAL AND METHODS

The mice were randomly sorted into 5 groups (10 each): 1st normal group received subcutaneous normal saline and intragastric distilled water, 2nd naringin 300 mg/kg orally, 3rd D-galactose (200 mg/kg/day) was administered subcutaneously into mice for eight weeks, to accelerate aging, 4th & 5th: oral naringin (150, 300 mg/kg) was given daily concurrently with D-galactose injection for 8 weeks.

KEY FINDING

In silico investigation revealed that naringin substantially stimulates the SIRT1 and AMPK molecules. At the molecular level, our findings indicated that treatment with naringin stimulated the mitochondrial biogenesis pathway through regulation of the LKB1/AMPK/PGC-1α signals and upregulated FOXO1-mediated autophagy. Furthermore, naringin exhibited antioxidant properties by activating the Nrf2/NQO1 pathway and inhibiting MDA and AGEs levels. In addition, Naringin ameliorated alveolar spaces destruction and bronchial wall thickening, as well as alleviated P53/caspase-3 apoptosis signaling.

SIGNIFICANCE

Naringin exerts protective effects against D-galactose-induced lung aging and enhances longevity by activating SIRT1. SIRT1 regulates various aging-related molecular pathways via restoring pro-oxidant/antioxidant homeostasis, activation of mitochondrial biogenesis, modulating of autophagy and inhibition of apoptosis.