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

suppresses the lipopolysaccaride (LPS)-induced production of nitric oxide in macrophages and was shown to decrease iNOS mRNA and its protein expression by inhibiting NF-ĸ B/Rel activation. 68 In the inactive state, NF-ê B remains complexed to the inhibitory protein I- ĸB. However, upon activation by various signals, NF-ĸB can translocate to the nucleus and bind to the kappa B motif of the target gene.63 Silymarin has been shown to inhibit many steps in the NF-ĸB pathway; it blocks TNF alpha and UVinduced activation of NF-ĸB, translocation to the nucleus and ĸ B DNA binding and gene expression. Interestingly, the effects of silymarin on NF-ĸB activation are specific, and do not impact AP-1 activation. Silymarin can also inhibit the TNF-induced activation of MAP kinase kinase and c-jun kinase and mitigated TNF-induced cytotoxicity and caspase activation.69,70
Topical administration
Polyphenols can be obtained through both diet and oral supplementation but these methods are limited by poor systemic bioavailability and variability of gut metabolism.16 Supplementing skin with a topical antioxidant is a more intuitive way of directly replenishing the skin’s endogenous antioxidants that are depleted from constant UV exposure.71 Various studies have shown that there is a greater amount of antioxidants in the epidermis compared to the dermis as the epidermis is in direct contact with oxidative stressors. However, due to irradiation damage, antioxidant activity in the upper layers of the stratum corneum decreases over time.72 Topical polyphenol formulations have been shown to have good permeability in the stratum corneum, with higher concentrations in the outermost layer, thereby targeting the site of antioxidant loss.72 In one study evaluating the penetration of polyphenols into the stratum corneum and underlying tissue, 90% of phenolic content was retained in the stratum corneum, with only 10% in underlying tissue. Catechins had greater permeability compared to curcumin and resveratrol, but this observed effect was greatly impacted by solubility in the delivery vehicle chosen.71 Passive delivery of polyphenol extracts is greatly dependent on the formulation, which affects the permeability of the active agent into deeper skin layers. The most common delivery agents currently employed are gels or emulsions, which have shown efficacy for topical polyphenol delivery. 15 As antioxidants are inherently unstable, creation of a stable formulation has been a challenge.14 Proper investigation into the optimal concentration and formulation is required for standardization and maximization of polyphenol delivery to skin.


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. These natural agents have broad anti-inflammatory and anti-oxidative properties, targeting many different cellular responses to ROS stimulation. Though most of the evidence for the protective effects of polyphenols are derived from in vitro and animal studies, epidemiologic studies do suggest an improvement with polyphenolic supplementation on cardiovascular markers in particular. Continued research into bioavailability and function of these agents will help translate their therapeutic potential to treat clinical disease.


Adam Friedman has been an investigator, consultant, or speaker for Johnson & Johnson, Amgen, Valeant, Onset, Loreal, and Salvona. Holly Gunn and Aimee Krausz have not disclosed any relevant conflicts.


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