Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 2 • February 2013


Chronic Inflammation and Superoxide Radicals Produced by NADPH Oxidase Are Reported to be the Main Determinants of Physical Frailty in Older Adults

A new study1 reports that physical frailty (assessed on the basis of gait speed) in 280 ambulatory elderly (over 60 years of age) is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.

In the studied group, 64% of patients had a walking speed less than 0.8 meter/second. The higher prevalence of slow walkers in the subjects studied here as compared to some other studies is, the authors explain, probably due to the fact that 37% of the subjects were more than 83 years old. “Our group had already shown that inflammation and oxidative stress are linked in older people by reciprocal activations. Indeed, inflammation is accompanied by activation of NADPH oxidase, particularly through TNF-alpha, leading to overproduction of superoxide anion in stressful situations.”1

References

1. Baptista et al. Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults. Free Radic Res. 46(9):1108-14 (2012).

Procyanidins from Grapes Shown to Be Inhibitors of Human Endothelial NADPH Oxidase

A very useful new paper2 reports that procyanidin-rich grape pomace, a commonly available by-product of the wine industry processing of grapes, was found to be a natural inhibitor of NADPH oxidase.

As explained by the authors,2 NADPH oxidase expression and superoxide anion production were shown to correlate with the severity of atherosclerosis, plaque stability, oxidative stress in coronary artery disease, and plasma metalloproteinase-9 levels, suggesting that NADPH oxidase could be a target for reducing the risk of atherosclerosis. The authors, however, state that there are no inhibitors of this enzyme that can be used in therapeutics, nor are there any specific inhibitors of the enzyme isoforms. Thus, the researchers initiated this study hoping to identify a safe, natural inhibitor of NADPH oxidase; they focused on three different procyanidin-rich fractions from an aqueous extract of grape pomace that included skin, seeds, and a small number of stems. These were compared to the effects of two known NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin.

Interestingly, there was a differential effect of the grape procyanidin-rich fractions on NADPH oxidase and on superoxide anion, in that the F4, F5, and F6 procyanidin fractions (10–100 ng/ml) inhibited NADPH oxidase activity in a concentration-dependent manner, yet only the highest concentrations of these fractions were effective as superoxide scavengers. Thus, the effects as superoxide scavengers and as inhibitors of NADPH oxidase were independent effects.

In addition, the researchers found that the three grape pomace procyanidin fractions were effective inhibitors of NADPH oxidase in living HUVEC (human umbilical vein endothelial cells), being active at both the extra- and intracellular level.

The authors claim that “[t]he NADPH oxidase inhibition activity described in our work for procyanidins from grape pomace has not been reported before, despite the inhibitor activity on this oxidase having been described for other components of grapes.” They cite, for example, a study in which polyphenols from grape extracts reduced NADPH oxidase subunit expression in human neutrophil mononuclear cells and in an endothelial cell line.

We are delighted that grape procyanidins were effective as NADPH oxidase inhibitors, as we have been on the lookout for a safe, effective and potent natural inhibitor of this enzyme for some time. The enzyme is hyperactive in the production of oxidative stress associated with many serious conditions, including cardiovascular disease and diabetes, and NADPH oxidase is the major source of superoxide anions in the vasculature.2

2. Alvarez et al. Procyanidins from grape pomace are suitable inhibitors of human endothelial NADPH oxidase. J Cell Biochem.

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