damage and has been shown to induce apoptosis in UV damaged
cells by shifting the bax/bcl-2 ratio in favor of apoptosis.
Both topical application and oral consumption protects against
UV induced carcinogenesis, and decreases carcinogenic markers
in tumors including CD31, VEGF, MMP-2, and MMP-9.42
Oats
Oats (Avena sativa) consist of a large range of phytochemicals
including carbohydrates, proteins, lipids, flavonoids, avenanthramides,
tocols, alkaloids, saponins, and sterols.43 Due to the
large lipid content, oat grains contain a variety of compounds
with antioxidant activity to prevent lipid peroxidation.44 These
primarily include glyceryl esters of caffeic and ferulic acids,
avenanthramides and alpha-tocopherol.45 Unique to oat grain
are avenanthramides, alkaloids that consist of anthranilic and
hydroanthranilic acid linked through an amide bond to one
of several hydroxycinnamic acids. Though only 0.06% of total
oat content, this bioactive element is a major source of the observed
anti-oxidant and anti-inflammatory properties of oats.
There are twenty-five structural varieties of avenanthramides,
but the three predominant types are formed from hydroxyanthranilic
acid and p-coumaric, ferulic, or caffeic acids.43,46
Oats have well-characterized cardioprotective effects, including
inhibition of atherosclerosis and hypertension and have
displayed anti-inflammatory, anti-pruritic, and antioxidant
activity when applied topically to the skin.46,47 The avenanthramides
possess elevated antioxidant activity compared to
other oat phenolic compounds, and seem to be the source
of oat’s antioxidant activity.48 Avenanthramides primarily act
via inhibition of NF-kB signaling by inhibition of IkB- degradation,
which subsequently decreases the production of
pro-inflammatory cytokines, such as IL-8.49 Dihydroavenanthramide
D, a synthetic analog of avenanthramides, was shown
to inhibit UVB-induced ROS generation, phosphorylation of
MAPKs, activation of NF-kB and AP-1, and MMP-1 and MMP-
3 expression.50 Oat bran extracts decreased H2O2-induced
human dermal fibroblast injury through the enhanced activity
of SOD and a decrease in the malondialdehyde (MDA)
level.51 A. sativa exerts anti-inflammatory activity by inhibiting
phospholipase A2 in keratinocytes, thereby decreasing
the release of the arachidonic acid from phospholipids and
subsequent eicosanoid formation.52,53 Topical application
of avenanthramides has also been found to reduce neurogenic
inflammation and edema associated with contact
hypersensitivity.49 The flavinoids in oats are another source
of anti-inflammatory activity, providing protection against
UVA radiation owing to their ability to absorb light in the
320-370nm range.44 Another component of oats, tocopherols
(vitamin E), has dual functionality as anti-inflammatory and
anti-photodamage agents and protects the skin from free
radical damage.54 These agents combined provide oats with
its unique therapeutic potential.
Curcumin
Curcumin, o-methoxyphenol derivative, is the bioactive component
of the spice, turmeric (C. longa), used for centuries in the
Ayurvedic tradition for its medicinal properties. Polyphenolic curcuminoids
constitute approximately 3% to 5% of most turmeric
preparations, and is the source of turmeric’s deep yellow color.55
Turmeric contains three major curcuminoids: curcumin (also
referred to as curcumin I or diferuloylmethane), desmethoxycurcumin
(curcumin II), and bisdesmethoxycurcumin (curcumin III).
There has been renewed interest in clinical translation of curcumin
due to its antioxidant, anti-inflammatory, wound healing and antibacterial
properties. Curcumin exerts anti-inflammatory activity
by inhibiting multiple levels of the NF-ĸB, AP-1, and JNK signaling
pathways, leading to decreased expression of pro-inflammatory
cytokines such as TNF-α, interleukins (IL-1, IL-2, IL-6, IL-8, IL-12) and
chemokines. In addition, curcumin has been shown to decrease
inducible nitric oxide synthase (iNOS) activity and the activation
of p38 MAPK.56,57 Curcumin acts on the arachidonic acid pathway
by inhibiting cyclooxygenase (COX)-2 expression and the downstream
synthesis of prostaglandin (PG)E2, and inducing apoptosis
in cells that constitutively express COX-2.58 One of the proposed
mechanisms for COX-2 inhibition is interference with the IĸK signalling
complex responsible for phosphorylation of IĸB and the
subsequent activation of NF-ĸB.59 Curcumin also acts as a potent
antioxidant by inhibiting ROS generation, scavenging O2– and
OH radicals, and increasing endothelial heme oxygenase-1 (HO-1)
protein expression and enzymatic activity.60,61 This protein, induced
by cellular stress, degrades heme to the anti-oxidant biliberdin
and carbon monoxide (CO) and is important in defending the
body against oxidant-induced injury. However, clinical application
of curcumin has been limited by to its low bioavailability, rapid
biodegradation, and bright yellow color when applied topically.
Silymarin
Silymarin is an extract of the milk thistle plant (Silybum marianum)
concentrated in the fruit and seeds, and is composed of
three flavinoids: silybin, silydianin, and silychristine. Silybin is
the most biologically active and constitutes 70-80% of the flavinoid
content. Silymarin is most known for its role in treating
hepatic disorders including alcoholic liver disease, cirrhosis and
hepatitis,62 effects due in part to its anti-inflammatory and antioxidant
properties.63 Silymarin has been shown to decrease
lipid peroxidation as a result of ROS scavenging and its ability
to increase the cellular content of glutathione (GSH).64 Both in
vitro incubation and in vivo treatment with silymarin resulted
in increased SOD expression,65 and it has displayed scavenging
activity against hydroxyl radicals, though not against hydrogen
peroxide or superoxide anion radical.66 Silymarin proved efficacious
in several models of oxidative stress to the liver, kidneys,
and pancreas, especially in reducing the toxic effects of free
radical generating drugs.63 Silymarin selectively inhibits the
5-lipoxygenase pathway, particularly leukotriene B4 (LTB4) formation,
with no effect on prostaglandin synthesis.67 Silymarin
