Epigallocatechin gallate (EGCG)

Introduction 

Epigallocatechin gallate (EGCG) is a natural plant-derived catechin that is predominantly found in tea. It is further classified as a polyphenol and is the compound responsible for many of the benefits in green tea and grape seed. The health benefits associated with drinking green tea and using cosmetics containing green tea are typically credited to its EGCG content.1 In skincare, it has noted benefits as an antioxidant preventing oxidative stress caused by UV damage. It has also been shown to improve skin hydration and elasticity by regulating hyaluronic synthase, the skin’s intrinsic means of producing hyaluronic acid. EGCG has been well-studied to show anti-oxidative, anti-acne, anti-inflammatory, and anti-microbial properties in the skin and emerging evidence of its anti-aging activity.2 

Catechins typically make up 30-40% of green tea leaves, dry weight, with EGCG the most abundant comprising 12% of that.3 Though, it is important to not confuse EGCG with green tea extract as extracts vary wildly in the concentration of active ingredients, with many often found to include over 90% water. This is why the use of pure compounds is strongly preferred in skincare. While EGCG is mainly sourced from green tea, it also exists in smaller amounts in oolong and black teas, fruits (e.g. kiwis, cherries, peaches, strawberries, apples), and nuts (e.g. pecans, pistachios, and hazelnuts).4

Benefits

EGCG is an all-around ingredient with multiple properties for skincare1:

• Hydration [1]
• Anti-acne [1,6]
• Anti-aging [1,7]
• Anti-inflammatory [1,6,7]
• Antioxidant [1,6]
• Brightening [1]
• Anti-microbial [1,6]
• Oiliness [6]

Studies have shown effective levels of topical EGCG at 0.5-1%, but it may also be effective at lower or higher levels. Safety assessments on the dermal use of green tea-extracted catechins do not indicate adverse reactions when they are examined on human skin. Concentrations of EGCG up to 1% are also safe by transdermal delivery.3 EGCG is easily oxidized and is prone to auto-oxidation at alkaline pH.4 This could result in its breakdown and lowered absorption if formulated with strong oxidizing agents. Fortunately, skincare products are formulated to take into account the chemical nature of each ingredient and ensure their stability under the recommended storage conditions and shelf life.

Formulation Considerations

Cosmetic formulations use a combination of compatible ingredients to target various skin concerns, improve permeation, maintain chemical stability, and promote synergism to enhance the benefits. When EGCG is delivered to human skin cells by nano-transfersomes formulated with hyaluronic acid, they work synergistically as protective agents against UV radiation damage and impart antioxidant and anti-aging properties.5,8 On the contrary, reactivity with incompatible ingredients formulated or used in combination with EGCG could also influence product stability, effectiveness or even cause adverse effects. For example, sodium dehydroacetate, an anti-fungal preservative found in some cosmetics, dramatically degrades EGCG following UV irradiation. This is based on known reactivity between sodium dehydroacetate and reducing agents and the easily oxidized nature of EGCG.5 When the stability of an ingredient is impacted by photoreactivity or other stimuli, less of it is available for absorption and function in the skin. EGCG is also heat-labile and must be kept under controlled temperatures.9 This is why it is important to store your skincare according to the instructions provided on product labels.

Biochemical Details 

The distinct polyphenol structure of EGCG imparts chemical mechanisms behind its important biological functions. The phenol rings act as electron traps and scavengers of free radicals. The goal is to inhibit the formation of reactive oxygen species to reduce any harm caused by oxidative stress during inflammation, injury, and UV damage. Each function has its unique biochemical pathway, and the most well-understood processes are its anti-inflammatory, antioxidant, anti-cancer, and anti-aging activity.

Anti-Aging: Skin hydration, Moisture Retention, Minimizing Wrinkle Formation

Skin aging can be attributed to several intrinsic factors like decreased moisture retention and proliferative activities of skin cells. These events lead to reduced synthesis of collagen and elastin and ultimately the appearance of dehydrated skin and wrinkle formation. Hyaluronic acid (HA) is a key molecule involved in skin hydration and promotes cell proliferation and differentiation during wound healing. It also regulates the hyaluronic acid synthase (HAS) genes. Natural moisturizing factors (NMFs) are important for maintaining the skin moisture barrier and are composed of HA, filaggrin (FLG), and transglutaminase (TGM)-1.2 The mechanisms by which EGCG promotes skin hydration and moisture retention influence the expression of HAS, hyaluronidase (HYAL), and NMF-related genes. In cell culture studies, EGCG can augment the expression of FLG, TGM-1, and HAS. An increase in moisture retention capacity is also confirmed by observing decreased levels of HYAL, an enzyme that hydrolyzes HA. In other words, EGCG can inhibit the degradation of HA in the epidermis by reducing the level of HYAL expression. These effects of EGCG help maintain the skin barrier more firmly and improve moisture retention. Moreover, it can increase cell proliferation and is an effective anti-wrinkle agent depending on the formulation.

Collagen is an essential component of the skin moisture barrier, and its distinct triple helical structure imparts stability and biological functions. Collagenase is an enzyme that is naturally produced in the body to specifically hydrolyze the triple helical structure of collagen, thus, destroying its stability and function. It has been shown that EGCG can effectively combat this by forming hydrophobic interactions and hydrogen bonds with collagenase.12 These EGCG-collagenase interactions block the collagenase active site to inhibit enzymatic activity and ultimately prevent collagen degradation. 

Anti-inflammatory

The main events that occur during an inflammatory response are the spike in pro-inflammatory cytokines, free radicals, reactive oxygen species (ROS), and immune cell aggregation at the site of inflammation. Therefore, EGCG targets the key molecules that are involved in these processes. An early event in the inflammatory response is the accumulation of ROS and RNS, which activates transcription factors nuclear factor (NF)-κB and activator protein (AP)-1. These transcription factors then move from the cytoplasm to the nucleus and upregulate various inflammatory gene expressions. This initiates the signal transduction pathway to upregulate other inflammatory gene expression and immune cell differentiation and proliferation. Interleukin (IL)-8 is a cytokine produced in response to inflammation and is reported to stimulate neutrophil aggregation and increase ROS production.12 A role of EGCG as an anti-inflammatory agent is to inhibit IL-8 production and reduce the severity of inflammation. The pain that usually accompanies inflammation is also managed by the application of EGCG as it downregulates the expression of pro-inflammatory genes mediated by the P2X4 receptor, a receptor responsible for inducing and aggravating chronic pain.

In mice models, topical EGCG can improve UVB-induced immunosuppressive events such as reducing the number of CD11b+ monocytes and neutrophils migrating to the skin inflammatory lesions. Additionally, EGCG inhibits the transfection of NF-κB and AP-1 to downregulate the expression of inducible nitric oxide synthase (iNOS) and COX-2 enzymes by scavenging nitric oxide (NO), peroxynitrite, and other reactive oxygen and nitrogen species.2 These reactions are coupled with the decrease in the production of pro-inflammatory factors that aggravate inflammation.

Antioxidant

The antioxidant defense mechanisms protect our skin from damage caused by stressors such as chronic UV exposure, environmental irritants, injury, and hypoxia. These events trigger oxidative stress and elevated levels of free radicals, which enhance the progression of skin aging, wrinkling, and pigmentation. While moderate levels of free radicals and ROS are normally produced as part of our immune defense, constant uncontrolled and excessive production promotes the development of inflammatory diseases, premature skin aging and skin cancer.2 EGCG protects our cells from damage associated with oxidative stress by reducing the levels of ROS that are produced in our body, thereby inhibiting cell death and suppressing the activity of pro-inflammatory cytokines such as TNF-α.13 

EGCG regulates cellular activity, including cell proliferation, differentiation, immune function, and apoptosis, by increasing the phosphorylation of p38, ERK, and JNK.12 In cell culture models, a preventive effect against radical-induced damage is observed by downregulating pro-apoptotic enzymes caspase-3 and caspase-8.2 Topical treatment of EGCG in mice models is also able to downregulate UVB-induced oxidative stress such as lipid peroxidation and protein oxidation. 

The phenol rings in EGCG act as electron traps and scavengers of free radicals to inhibit the formation of reactive oxygen species. Due to the easily oxidized nature of EGCG, it reacts readily with the superoxide anion (O2-) radicals produced during oxidative stress. It becomes oxidized on the B and D rings of the polyphenol structure. Small quantities of ROS are produced during the antioxidant activity of EGCG, but this serves to activate signal pathways and cellular protective mechanisms. Nitro-oxidative stress-induced cell damage can also be prevented through its activity by inhibiting protein tyrosine nitration.12 The auto-oxidation tendency of EGCG can also form covalent bonds with cysteinyl thiol residues of proteins to modulate their function in cancer treatment, and inhibit angiotensin-converting enzyme (ACE) enzyme to treat cardiovascular diseases.14 

Preventing UV-Induced Skin Damage, Anti-Pigmentation

Environmental stressors such as UV radiation and air pollution are examples of extrinsic factors that contribute to skin damage and aging. Melanin synthesis is a natural process in the body to protect our skin from external stress. However, excessive production from prolonged UV exposure can cause age spots. To prevent and minimize this effect, cosmetics are formulated with compounds that downregulate melanin synthesis as anti-pigmentation constituents. In cell models, EGCG is able to significantly reduce melanin secretion induced by α-melanocyte-stimulating hormone (αMSH) and UV exposure.18 This suggests that EGCG can be used as an anti-hyperpigmentation active in skincare. 

Penetration

EGCG is overall well-absorbed via the dermal route. It is safe at concentrations up to 1%, the typical amount in most cosmetics. EGCG emulsions tend to have better absorption than gel formulations.5 Nano-transferomes that are formulated with hyaluronic acid have effective absorption in addition to potent anti-aging and antioxidant activity.8  

Abbreviations and Terminologies

References

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