Opuntia ficus indica (L.) fruit extract alleviates oxidative stress through activation of dual oxidases and Keap1/Nrf2 signaling cascades in high-fat-diet associated atherosclerosis rats.

Atherosclerosis is a metabolic disorder characterized by chronic inflammation associated with progressive thickening and hardening of the large to medium-sized arteries due to plaque formation. The study aims to evaluate the antioxidative, anti-inflammatory, and hypolipidemic efficacy of (OFI) fruit extract against the high-fat-diet associated atherosclerotic rat model. qualitative and quantitative phytochemical screening of OFI fruit extract revealed the significant presence of total phenolic content and total flavonoid contents. antioxidant activity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl and FRAP assays that have shown their protective efficacy against the overproduction of reactive oxygen species. Results revealed that the level of total oxidant stress was significantly ( < 0.05) reduced and down expression levels of dual oxidases (Duox, Duoxa-1, and Duox-2) in all the treatment groups (I, II, III) as compared with positive control were observed. The total antioxidant capacity was significantly ( < 0.05) increased in all treatment groups in comparison with the positive control group and higher expression level of the Nrf-2 signaling pathway (Nfe-212, NFR-1, and Keap-1) was observed in all the treatment groups compared with the positive control group. Histopathological examination of the aorta showed that high-fat diet markedly increased endothelial lining and thickness of tunica media and adventitia, with irregular media segments having wavy laminae, and a significant increase in entropy of fibers disposition was observed. Conclusively, OFI fruit extract has shown promising protective, anti-oxidative, and anti-inflammatory efficacy through the restoration of normal parenchyma in high-fat dieting-associated oxidative stress and endothelial inflammation.