Synergistic effects of dietary bioactive compounds and investigation of Nrf2/HO-1 axis in HIV-1 transgenic rat

Considerable evidence suggests that the combinatorial effect dietary bioactive compounds may be useful in preventing or reducing aging features. Therefore, a synergistic multi-target approach in dietary intervention may be effective in slowing down the aging process and increase healthy aging. Functional foods and nutraceuticals can exert specific anti-aging benefits such as improvement in mitochondrial function or induce neuroprotective effects to counteract the deleterious consequences of oxidative stress. In this project, we evaluated a novel treatment strategy by combining two bioactive dietary constituents (resveratrol and equol) to determine their effect on mitochondrial function. The combined use of both compounds increased mitochondrial mass, mitochondrial DNA content, SIRT1 enzymatic activity and induced mitochondrial biogenesis factors such as PGC1-α, TFAM and NRF-1. Therefore, identification of this novel synergism may provide a new perspective for future treatments aiming to modulate the mitochondrial activity. Next, we investigated the combined effect of L-Carnosine and EGCG, two bioactive dietary compounds that have received particular attention because of their potential role in modulating oxidative stress associated with aging. We demonstrated that the neuroprotective effects of EGCG and L-Carnosine are achieved through the modulation of HO-1/Hsp72 systems. Our results indicate that the combined administration of EGCG and L-Carnosine reduces the neuronal damage caused by oxidative stress. Since chronic oxidative stress plays a central role in the pathogenesis of many diseases, including HIV-1 associated disorders, the last part of the project aimed to investigate the age-related patterns of Nrf2 and HO-1 in different brain regions and tissues of HIV-1 transgenic rat. The Nrf2/HO-1 axis constitutes a crucial cell survival mechanism to counteract oxidative stress and several recent studies have shown that bioactive food compounds can modulate Nrf2/HO-1 pathway. However, in the context of HIV-1 infection its role remains largely uncharacterized. In HIV-1 transgenic rat, we observed a significant reduction in the protein levels of Nrf2 and HO-1, suggesting a weakening in the cytoprotection exerted by Nrf2/HO-1 system. Moreover, the declined protein function of Nrf2 and HO-1 was accompanied by the acquisition of premature senescence phenotype in HIV-1 transgenic rat. Dietary inducers of Nrf2 and HO-1 may provide a novel strategy for restoring this pathway and mitigate oxidative stress during HIV-1 infection.