Lipid-soluble green tea polyphenols: Stabilized for effective formulation

Green tea polyphenols (GTPs), also referred to as green tea catechins, possess properties that can provide unique health benefits to humans. As indicated in other chapters of this book, studies using molecular, cellular, and animal models, and in human subjects, have demonstrated that these phytochemicals from non-oxidized tea leaves have anti-cancer, anti-oxidant, anti-microbial, and anti-inflammatory properties. Recently, investigations in our and other laboratories indicated that topical application of GTPs could protect the epidermis against autoimmune disorders, such as psoriasis, prevent or repair UV-induced damage, and suppress scar tissue overgrowth. In addition, specific gene regulation by GTPs, especially epigallocatechin-3-gallate (EGCG), promotes skin cell differentiation, which could lead to improved homeostasis of the skin. Based on these facts, the topical use of products containing GTPs has become more popular, and manufacturers of cosmetic, health care, and household products are adding GTPs or EGCG to their formulations. However, it is important to note that studies described in this book always use "freshly prepared" GTPs or green tea, instead of "pre-prepared materials". This is because GTPs are potent antioxidants that react rapidly with reactive oxygen species (ROS). As a result, GTPs in most commercially available products have been oxidized and/or epimerized; the biological effects of the resulting compounds are largely unknown. In addition, due to the highly water-soluble nature of these compounds, GTPs in their original form are not lipid-soluble, and therefore not permeable to the skin, a water-proof barrier. Another problem with formulation of GTPs for topical application is the coloration change and precipitation caused by oxidation. Thus, GTPs for topical application (e.g., on skin and mucous membranes) must be prepared and used immediately prior to oxidation, coloration and precipitation. These properties of GTPs make it difficult to formulate products containing them that have a reasonable shelf life and maintain their activity and effectiveness. In other words, most of the commercially available "green tea"-containing products are without the full benefits of green tea or GTPs. Therefore, strategies to stabilize and increase the bioavailability of GTPs are needed to provide the full benefits of GTPs to consumers or patients. Recently, it has been shown that lipid esters of GTPs can be formed either enzymatically or chemically. These green tea polyphenol-lipid esters, also referred to as lipid-soluble tea polyphenols (LTPs), could significantly improve formulations of consumer or health care products. We hypothesized that fatty acyl esterification of green tea polyphenol would protect the hydroxyl groups from oxidation and improve skin permeability. In the current study, we compared the activities of LTPs to GTPs for their anti-cancer and gene regulation properties. We examined whether LTPs can be converted into a free GTP (EGCG) in human skin keratinocyte cultures. In addition, the effects of LTPs in a mouse model for psoriasis were evaluated. The results indicate that LTPs effectively cause cancer cell death, induce caspase 14 gene expression both in vitro and in vivo, and improve the skin condition in an animal model for psoriasis. Consistent with these observations, HPLC analysis demonstrated that EGCG in its original form was released from LTPs in situ by human epidermal keratinocytes. These results suggest that LTPs, under appropriate conditions, function similarly to GTPs. More importantly, since the most reactive hydroxyl group(s) is/are protected, and the lipid solubility is dramatically increased by the fatty acyl groups, the biological activity of these compounds can be stabilized, and their bioavailability increased significantly. In conclusion, LTPs are a novel and more effective form of green tea polyphenols for topical applications and other purposes, especially in formulations that require a reasonable shelf life. In addition, LTPs can be a natural additive to consumable products such as salad oil, fish oil, and cooking oil as antioxidants.