INTRODUCTION
Herbal medicine, also referred to as botanical medicine
and phytomedicine, has steadily gained popularity as
an alternative to conventional, synthetic drug use.1 In
2007, 1 out of 4 adults reported trying complementary and alternative
medicine (CAM), of which nonvitamin, nonmineral, natural
products were the most commonly used therapies.2 Of note,
the prevalence of CAM use was significantly higher in adults
with skin disease (49.4%) as compared to the general population
(36.0%).3 In dermatologic practice, natural products are
particularly sought after by patients for the treatment of chronic
diseases such as acne, psoriasis and atopic dermatitis, and
have become an integral component of the cosmeceutical industry.
4 The production and distribution of botanical extracts is
largely unregulated and therefore extensive research into their
mechanism of action, safety, physiologic stability and optimal
dosing has been overlooked. However, despite the scarcity of
rigorous clinical scientific data, utilization of these agents is justified
by personal experience as well as their potential to target
oxidative and inflammatory processes at the root of many skin
diseases.4 Elucidation of the molecular targets of these natural
ingredients is essential for application in the setting of disease
and prevention of adverse side effects and drug interactions.
The Impact of Oxidative Stress
Many natural agents target reactive oxygen species (ROS), which
are generated as a byproduct of endogenous biologic processes
and from environmental exposures, such as ultraviolet radiation,
pollutants and xenobiotics.5 ROS are defined as oxygen compounds
that have a reactivity greater than that of molecular
oxygen and include superoxide anion (O2-), hydrogen peroxide
(H2O2), hydroxyl radical (OH-) and singlet oxygen (O2). At low concentrations,
ROS exert beneficial effects by mounting a response
against pathogenic organisms, inducing cellular proliferation and
functioning in cell signaling pathways.6 However, oxidative stress
occurs when the production of ROS outpaces the inherent cellular
antioxidant defense system.7 This imbalance causes direct
damage to DNA via oxidation of pyrimidine bases and singlestranded
breaks, destruction of the cellular membrane due to
lipid peroxidation, and interference with the structure and function
of proteins due to modification of amino acids, particularly
cysteine residues (Figure 1).6 The accumulation of such extensive
damage promotes pro-apoptotic signaling and subsequent
cell death. In addition, ROS generate an inflammatory mileu by
promoting the activation of transcription factors, such as nuclear
factor (NF)-ĸB and activator protein 1 (AP-1), and the mitogen activated
protein kinase (MAPK) signal transduction cascade (ERK,
JNK, and p38 pathways).7,8 NF-kB upregulates transcription of proinflammatory
mediators, such as interleukin (IL)-1, IL-6, IL-8, and
tumor necrosis factor-alpha.9 Acting through the cell surface, these
mediators generate a state of sustained inflammation by further
activation of AP-1 and NF-kB. UV-induced MAPK signaling leads to
increased expression of AP-1 via stimulation of cjun, a protein that
combines with cfos to form the active AP-1 protein. This in turn
leads to the upregulation of matrix metalloproteinases (MMP),
which degrade the extracellular matrix (collagen and elastin) of
the dermis and is responsible for photodamaging effects to skin.10
