The Basic Science of Natural Ingredients

August 2014 | Volume 13 | Issue 8 | Original Article | 937 | Copyright © August 2014

Aimee Krausz,a Holly Gunn MD,b and Adam Friedman MD FAADa,c

aDivision of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
bLancaster Skin Center, Lancaster, PA
cDepartment of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY

Herbal products have steadily gained popularity as alternatives to conventional, synthetic medications and are sought after by patients for the treatment of chronic dermatologic diseases and for cosmeceutical use. 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. One of the major pathways through which natural supplements, particularly polyphenols, act is via inhibition of oxidative stress and its downstream mediators. Endogenous defense mechanisms are inadequate to combat oxidative stress and therefore dietary and/or topical supplementation with polyphenols are an important complementary preventative and therapeutic strategy. This review focuses on the molecular targets of common polyphenols used in topical preparations, particularly soy, green tea, oats, curcumin, and silymarin. Continued research into bioavailability and function of these agents will help translate their therapeutic potential to treat clinical disease.

J Drugs Dermatol. 2014;13(8):937-943.


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