Supporting Research

Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model

Abstract: 

We investigated the effect of topical epigallocatechin-3-gallate (EGCG) on testosterone (T)-induced hair loss in mice. Marked hair loss was observed at the T-injected site, and topical EGCG significantly reduced the hair loss (P < 0.05). TUNEL staining showed apoptosis of follicular epithelial cells in the T-injected groups where topical EGCG was found to significantly diminish T-induced apoptosis (P < 0.05). Topical EGCG down regulated the T-induced expression of androgen receptor but did not down-regulate 17b-hydroxysteroid dehydrogenase (HSD) and

A Proprietary Topical Preparation Containing EGCG-Stearate and Glycerin with Inhibitory Effects on Herpes Simplex Virus: Case Study

Abstract: 

The effects of a proprietary topical formulation containing EGCG-stearate in 100% glycerin USP were studied in two volunteer patients with recurrent herpes simplex (HSV) type 1. Application during early onset (prodromal stage) in a patient with herpes labialis prevented lesion progression. In a second patient with herpetic stomatitis, application of the formula during a later stage (inflammation stage) led to a remarkably shortened duration of symptoms.

Green Tea and Skin Protection

Abstract: 

Many products currently on the market aim, in one way or another, to apply basic science discoveries obtained using fresh preparations of green tea materials to skin conditions via formulations that of necessity must have a shelf life. However, what is not appreciated fully is the  instability of aqueous green tea preparations, and their relative impermeability in skin.  this perspective examines some of the difficulties in translating basic science knowledge into efficacious commercial skin products, outlines some potential clinical applications, and describes

Green Tea Polyphenols: Versatile Cosmetic Ingredient

Abstract: 

The research and development of cosmeceuticals is booming in recent years. Many substances, from botanical are tested or investigated as the active ingredients in cosmeceuticals. Green tea polyphenols have gained high popularity in cosmetic arena for their skin improving property. This review is an attempt to collect the scientific data of green tea polyphenols on major cosmetic problems like aging, wrinkle, photodamage, skin darkness, acne, dandruff and hair loss.

Green tea polyphenols reduce autoimmune symptoms in a murine model for human Sjogren’s syndrome and protect human salivary acinar cells from TNF -α- induced cytotoxicity*

Abstract: 

Sjogren’s syndrome (SS) is a relatively common autoimmune disorder. A key feature of SS is lymphocytic infiltration of the salivary and lacrimal glands, associated with the destruction of secretory functions of these glands. Current treatment of SS targets the symptoms but is unable to reach or prevent the damage to the glands. We reported previously that the major green tea polyphenol (GTP) epigallocatechin -3- gallate (EGCG) inhibits autoantigen expression in normal human keratinocytes and immortalized normal human salivary acinar cells (Hsu et al. 2005).

A New Approach to Managing Oral Manifestations of Sjogren’s Syndrome and Skin Manifestations of Lupus

Abstract: 

 

Sjögren’s syndrome (SS) is an autoimmune disorder thataffects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epidermis. Recent studies have demonstrated that green tea polyphenols (GTPs) possess both anti-inflammatory and anti-apoptotic properties in normal human cells. Epidemiological evidence has indicated that, in comparison to the United States, the incidence of SS, clinical xerostomia and lupus is considerably lower in China and Japan, the two leading green tea-consuming countries.  Thus, GTPs might be responsible, in part, for geographical differences in the incidence of xerostomia by reducing the initiation or severity of SS and lupus. Consistent with this, molecular, cellular and animal studies indicate that GTPs

could provide protective effects against autoimmune reactions in salivary glands and skin. Therefore, salivary tissues and epidermal keratinocytes could be primary targets for novel therapies using GTPs. This review article evaluates the currently available research data on GTPs, focusing on their potential application in the treatment of the oral manifestations of SS and skin manifestations of SLE. 

Psoriasis is Characterized by Altered Epidermal Expression of Caspase 14, a Novel Regulator of Keratinocyte Terminal Differentiation and Barrier Formation

Abstract: 

Caspases are a family of cysteine proteases involved in the effector arm of physiologic cell death [1]. In 1998, a novel caspase designated ‘‘caspase 14’’ was described in embryonic and adult tissues, especially epidermal keratinocytes [2—4]. Unlike other caspases (such as 3, 6 and 7), caspase 14 is not processed by typical death stimuli or activated during apoptosis induced by ultraviolet irradiation or cytotoxic substances. However, caspase 14 is cleaved under conditions leading to terminal differentiation, suggesting a unique role in keratinocyte ‘‘planned cell death’’ in forming the stratum corneum [2,5]. We postulated that psoriasis, a chronic papulosquamous disease with aberrant epidermal proliferation and terminal differentiation [6], may express altered levels of caspase 14.

Green Tea Polyphenol Induces Caspase 14 in Epidermal Keratinocytes via MAPK Pathways and Reduces Psoriasiform Lesions in the Flaky Skin Mouse Model

Abstract: 

Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. The expression and proteolytic processing of caspase 14, a member of the caspase family which is associated with epithelial cell differentiation, planned cell death, and barrier formation, is altered in psoriatic epidermis. We recently reported that human psoriatic tissues lack normal expression of caspase 14 [J Dermatol Sci 37 (2005) 61], and caspase 14 is induced by EGCG, a green tea polyphenol (GTP), in exponentially growing normal human epidermal keratinocytes (NHEK) [J Pharmacol Exp Ther 315 (2005) 805]. This suggests that GTPs may have beneficial effects on psoriasiform lesions. The current study aimed to determine whether MAPK pathways are required for GTP-induced caspase 14 expression in NHEK and if GTPs can modulate the expression of pathological markers in the psoriasiform lesions that develop in the flaky skin mouse. The results indicate that the p38 and JNK MAPK pathways are required for EGCG-induced expression of caspase 14 in NHEK. Importantly, topical application of 0.5% GTPs significantly reduced the symptoms of epidermal pathology in the flaky skin mice, associated with efficient caspase 14 processing and reduction in proliferating cell nuclear antigen levels. This suggests that GTP-activated pathways may be potential targets for novel therapeutic approaches to the treatment of some psoriasiform skin disorders.

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Abstract: 

Protection of glandular acinar cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. EGCG (the most abundant green tea polyphenol) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties. To investigate if EGCG can protect against certain autoimmune-induced pathological changes in the salivary glands of the nonobese diabetic (NOD) mouse model for SS-like symptoms, animals were provided with either water or water containing 0.2% EGCG. At the age of 8, 16 and 22 weeks, samples were collected for pathological and serological analysis. Massive lymphocyte infiltration was observed in the salivary glands of the water-fed group at the age of 16 weeks, while the EGCG group showed significantly reduced lymphocyte infiltration.  By 22 weeks of age, animals fed with water demonstrated elevated levels of apoptotic activity within the lymphocytic infiltrates, and high levels of serum total anti-nuclear antibody, in comparison with the animals fed with EGCG. Remarkably, proliferating cell nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of NOD animals fed with water were significantly elevated in comparison to BALB/c control mice; in contrast, PCNA and Ki-67 levels in EGCG-fed NOD animals were similar to BALB/c controls. These results indicate that EGCG is able to protect the NOD mouse submandibular glands from autoimmune-induced inflammation, and reduces serum autoantibody levels. Abnormal proliferation, rather than apoptosis, appears to be a characteristic of the NOD mouse gland that is normalized by EGCG. The evidence suggests that EGCG could ultimately be used to delay or manage SS-like autoimmune disorders.

Green Tea and Skin Protection: Mechanism of Action and Practical Applications

Abstract: 

Many products currently on the market aim, in one way or another, to apply basic science discoveries obtained using fresh preparations of green tea materials to skin conditions via formulations that of necessity must have a shelf life. However, what is not appreciated fully is the instability of aqueous green tea preparations, and their relative impermeability in skin. This perspective examines some of the difficulties in translating basic science knowledge into efficacious commercial skin products, outlines some potential clinical applications, and describes a recent advance that points a way towards a strategy to improve commercial formulations.

Green Tea and the Skin

Abstract: 

Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action. ( J Am Acad Dermatol 2005;52:1049-59.)

Green Tea Polyphenols Induce Differentiation and Proliferation in Epidermal Keratinocytes

Abstract: 

The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), was found to induce differential effects between tumor cells and normal cells. Nevertheless, how normal epithelial cells respond to the polyphenol at concentrations for which tumor cells undergo apoptosis is undefined. The current study tested exponentially growing and aged primary human epidermal keratinocytes in response to EGCG or a mixture of the four major green tea polyphenols. EGCG elicited cell differentiation with associated induction of p57/KIP2 within 24 h in growing keratinocytes, measured by the expression of keratin 1, filaggrin, and  ransglutaminase activity. Aged keratinocytes, which exhibited low basal cellular activities after culturing in growth medium for up to 25 days, renewed DNA synthesis and activated succinate dehydrogenase up to 37-fold upon exposure to either EGCG or the polyphenols. These results suggest that tea polyphenols may be used for treatment of wounds or certain skin conditions characterized by altered cellular activities or metabolism.

Green Tea Polyphenol-Induced Epidermal Keratinocyte Differentiation Is Associated with Coordinated Expression of p57/KIP2 and Caspase 14

Abstract: 

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry.  In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period.  The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor- 1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas.  These results suggest that, in addition to p57/KIP2, EGCGinduced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.

Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells

Abstract: 

Autoimmune disorders, characterized by inflammation and apoptosis of target cells leading to tissue destruction, are mediated in part by autoantibodies against normal cellular components (autoantigens) that may be overexpressed. For example, antibodies against the autoantigens SS-A/Ro and SS-B/La are primary markers for systemic lupus erythematosus and Sjo¨ gren’s syndrome. Recently, studies in animals demonstrated that green tea consumption may reduce the severity of some autoimmune disorders, but the mechanism is unclear.  Herein, we sought to determine whether the most abundant green tea polyphenol, ()-epigallocatechin-3-gallate (EGCG), affects autoantigen expression in human cells. Cultures of pooled normal human primary epidermal keratinocytes and of an immortalized human salivary acinar cell line were incubated with 100 M EGCG (a physiologically achievable level for topical application or oral administration) for various time periods and then analyzed by cDNA microarray analysis, reverse transcription-polymerase chain reaction, and Western blotting for expression of several major autoantigen candidates. EGCG inhibited the transcription and translation of major autoantigens, including SS-B/La, SS-A/Ro, coilin, DNA topoisomerase I, and -fodrin. These findings, taken together with green tea’s anti-inflammatory and antiapoptotic effects, suggest that green tea polyphenols could serve as an important component in novel approaches to combat autoimmune disorders in humans.

EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: Role of c-Jun N-terminal kinase

Abstract: 

The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57 often is associated with advanced tumors, and tumor cells with inactivated p57 undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is not well understood.