|
چکیده
|
ABSTRACT The rapidly growing aging population underscores the necessity of creating effective anti-aging treatments. Grape seed extract (GSE) is recognized for its antioxidant capabilities. Age-related hepatic decline is driven by oxidative stress and inflammation. This study investigated the protective mechanism of dietary GSE in a natural aging rat model, focusing on the microRNA-regulated Nrf2 pathway. Young female rats aged three months and older female rats aged twenty-four months were administered GSE (120 mg/kg) or a vehicle for a duration of 8 weeks. Liver function and histological changes were evaluated through serum ALT/AST levels and histological architecture. The oxidative status was assessed by measuring hepatic MDA levels and the activity of antioxidant enzymes. Apoptosis was analyzed using immune-histo-fluorescence for Caspase 3 and Bcl-2, while inflammation was measured via ELISA for NF-κB, IL-6, and TNF-α. The expression levels of miR-144, miR-200a, and the mRNA levels of the Nrf2, HMOX1 and NQO1 genes were quantified using RT-qPCR. Treatment with GSE significantly enhanced liver function and histological integrity in rats. It led to a reduction in MDA levels and an improvement in the antioxidant response, as indicated by increased HO-1 activity. GSE also effectively inhibited apoptosis by lowering caspase 3 levels and increasing Bcl-2 levels, as well as reducing inflammation by diminishing NF-κB, IL-6, and TNF-α levels. Mechanistically, GSE corrected the age-related dysregulation of the miRNA axis, resulting in the downregulation of miR-144 and the upregulation of miR-200a, which correlated with a significant increase in Nrf2, HMOX1 and NQO1 mRNA levels. Aging is associated with heightened oxidative stress, apoptosis, and inflammation in the liver; however, GSE demonstrated protective effects against these detrimental processes. It exhibits hepatoprotective properties by targeting the miR-144/200a regulatory axis to reactivate the antioxidant pathway. This fundamental mechanism supports the observed protective effects, offering a coherent therapeutic approach for age-related hepatic dysfunction.
|