The type of pathway activated depends on the source and duration
of the stress, as well as on the specific cell type and stage.11
The Innate Antioxidant Defense System
Many disease states, such as cancer, diabetes, aging and cardiovascular
disease have been linked to sustained oxidative
stress.12,13 To combat these damaging effects, the body has an
elaborate system of defense consisting of enzymatic (Figure 2)
and non-enzymatic antioxidants. The naturally occurring enzymes
include glutathione peroxidase, catalase, and superoxide
dismutase (SOD), all of which neutralize ROS. SOD catalyzes
the conversion of superoxide anion into hydrogen peroxide,
which can then be neutralized into water and molecular oxygen
by catalase and glutathione peroxidase (Figure 2). The skin has
non-enzymatic antioxidant reserves, including L-ascorbic acid,
glutathione, vitamin E, and ubiquinol.14 To combat depletion,
these physiologic antioxidants work in an integrated network
to regenerate each other in the process. Inherent antioxidant
mechanisms can be overloaded by excessive exposure to
stressors and age-related decreases in enzyme production and
function. Unfortunately, topical application of antioxidant enzymes
has failed due to compound instability, poor cutaneous
absorption and short-lived catalytic activity on the skin.15 Looking
for an alternate route, companies, and investigators have
turned to nature to identify supplemental antioxidants.
Natural Supplements
Plants are an intuitive source of antioxidants as they are
constantly forced to protect themselves from sun-induced oxidative
damage.14 Plants synthesize vitamin C, vitamin E, and
polyphenols, naturally occurring compounds with anti-inflammatory,
immunomodulatory, and anti-oxidant properties.16
Currently 8000 polyphenols have been identified, with the most
common sources being fruits, vegetables, whole grains, tea,
chocolate, and wine. Polyphenols are classified chemically according
to their phenolic structure, as well as the source of origin
and biologic function.17,18 Phenols exert antioxidant activity by a
few mechanisms. They neutralize free radicals by donating an
electron or hydrogen atom and act as direct radical scavengers of
lipid peroxidation chain reactions.19 In addition, polyphenols act
as metal chelators, particularly of Fe2+, reducing the rate of the
Fenton reaction and subsequent oxidation by reactive hydroxyl
radicals.20 They have been shown to induce endogenous antioxidant
enzymes and inhibit xanthine oxidase.21 Polyphenols also
