EGCG mediated downregulation of NF-AT and macrophage infiltration in experimental hepatic steatosis.

SCOPE: Increased fat consumption in industrialized countries has resulted in hepatic steatosis that upregulates atherogenic aspirant genes, leading to atherosclerosis and mortality. Although extensive studies have been carried out to elucidate the atheroprotective efficacy of epigallocatechin-3-gallate (EGCG), the effect of EGCG on hepatic steatosis has not been studied comprehensively. Hence, the current study was designed to find out the effect of EGCG on hepatic events that prelude atherosclerosis with special reference to macrophage infiltration. METHODS AND RESULTS: Male albino rats of Wistar strain were used in this study. Basic biochemical assays along with the protein expression of CAMs, NF-κB, TNF-α and NF-AT were assayed in the current study. EGCG supplementation significantly reverted the alterations in both biochemical and histological parameters and is shown to reduce the TNF-α mediated NF-AT expression and thereby its downstream targets like ICAM-1 and E-selectin expression to a greater extent than NF-κB mediated downstream targets like VCAM-1 and P-selectin in hypercholesterolemic rat liver. CONCLUSION: Our results suggest that EGCG influences the early events of atherosclerosis that occur; thereby modulating the NF-AT pathway and thereby mitigating the hypercholesterolemic stress.

Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart.

OBJECTIVES: Oxidative stress is recognized as a key element responsible for the development of age-related pathologies. A declining endogenous defence system during senescence dictates the need for supplementation with exogenous antioxidants through diet. Hesperidin is a naturally occurring flavonone present in citrus fruits and has been shown to have many biological properties, including antioxidant activity. We investigated whether hesperidin supplementation could be valuable in protecting cardiac tissue of aged rats against age-related increase in oxidative stress, as well as the mechanism by which it can boost the antioxidant status of the cell. METHODS: The activity of antioxidant enzymes, mRNA expression of Nrf2, protein levels of superoxide dismutase and catalase were measured using standard protocols. KEY FINDINGS: Hesperidin treatment effectively protected aged rat heart by increasing the activity of enzymic antioxidants. Hesperidin upregulated the protein levels of nuclear factor erythroid 2-related factor 2, which is responsible for maintaining the antioxidant status of the cell. CONCLUSIONS: Hesperidin could be useful in protecting cardiomyocytes against age-related increase in oxidative stress mediated by Nrf2 upregulation.