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 Opuntia ficus-indica (OFI) fruit extract against the high-fat-diet associated atherosclerotic rat model. In-vitro qualitative and quantitative phytochemical screening of OFI fruit extract revealed the significant presence of total phenolic content and total flavonoid contents. In-vitro 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 (P < 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 (P < 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.
