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

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 (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, 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 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