Effect of antioxidant supplementation on skeletal muscle and metabolic profile in aging mice.

Aging induces drastic changes in muscle mass and function (sarcopenia); however, the detailed mechanisms underlying sarcopenia remain poorly understood. Recent studies suggested that age-related increases in oxidative stress induce muscle atrophy. In this study, we investigated the effect of 6-month supplementation of antioxidants, specifically piceatannol (PIC) and enzymatically modified isoquercitrin (EMIQ), on age-related physiological changes, including skeletal muscle weight and quality, in 25-month-old (OLD) mice, compared to in 4-month-old (young, YNG) C57BL/6J mice. Muscle weight corrected by body weight significantly declined in OLD mice, compared to in YNG mice. The control OLD mice also showed changes in the expression of genes related to muscle fiber type, reduced locomotor activity, and increased oxidative stress markers in blood. Consistent with the muscle weight and quality changes, whole-body fat oxidation during sedentary conditions and exercise periods in control OLD mice was significantly lower than that in YNG mice. Interestingly, compared to the control OLD mice, the PIC- or EMIQ-fed OLD mice showed higher fat oxidation. Furthermore, EMIQ, but not PIC, increased locomotor activity, the expression of genes encoding antioxidant enzymes, and suppressed the carbonylated protein in the skeletal muscle of OLD mice. These results suggested that chronic antioxidant intake could alleviate aging-related muscle function changes.

Piceatannol and its metabolite, isorhapontigenin, induce SIRT1 expression in THP-1 human monocytic cell line.

Piceatannol is a phytochemical that is present in large amounts in passion fruit (Passiflora edulis) seeds, and is an analog of resveratrol. Recently, the absorption and metabolism of piceatannol were investigated in rats, and isorhapontigenin, O-methyl piceatannol, was detected as a piceatannol metabolite in rat plasma. To elucidate the function of piceatannol and its metabolites, we investigated the expression of sirtuin 1 (SIRT1) in THP-1 monocytic cells after treatment with piceatannol and its metabolites, and compared their effects with those of resveratrol and its metabolites. Piceatannol and resveratrol upregulated the expression levels of SIRT1 mRNA and SIRT1 protein. An extract of passion fruit seeds, which contained high levels of piceatannol, also upregulated SIRT1 mRNA expression. As for the metabolites, isorhapontigenin upregulated SIRT1 mRNA expression, whereas resveratrol glucuronides and sulfate did not affect SIRT1 expression. These findings indicate that after intake of piceatannol, not only piceatannol itself, but also its metabolite, isorhapontigenin, contributed to the upregulation of SIRT1 expression.

Effect of long-term piceatannol treatment on eNOS levels in cultured endothelial cells.

Piceatannol (3, 3', 4, 5'-tetrahydroxy-trans-stilbene) is a naturally occurring phytochemical found in passion fruit (Passiflora edulis) seeds. Previously, we demonstrated that piceatannol has acute vasorelaxant effects in rat thoracic aorta. It was suggested that endothelial NO synthase (eNOS) might be involved in piceatannol-induced acute vasorelaxation. Here, we investigated the expression of eNOS in EA.hy926 human umbilical vein cells after long-term treatment with piceatannol, and compared this effect with that of resveratrol, an analog of piceatannol. Long-term treatment with piceatannol up-regulated eNOS mRNA expression and increased eNOS protein expression in a dose-dependent manner. Moreover, piceatannol increased the levels of phosphorylated eNOS. Treatment with resveratrol also increased eNOS expression, but to a lesser degree than piceatannol. These findings indicate that piceatannol may improve vascular function by up-regulating eNOS expression.