Skin Care Research: Green Tea EGCG for DIY Skincare

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Advanced skin care research has shown that there are many health benefits to green tea egcg. It is often used as an antioxidant, an anti-inflammatory, and for sun damage protection/sun damage repair. One study also showed that it may be used to prevent and treat keloids (a mild non-cancerous form of skin tumor)

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Park G, Yoon BS, Moon JH, Kim B, Jun EK, Oh S, Kim H, Song HJ, Noh JY, Oh C, You S. Green Tea Polyphenol Epigallocatechin-3-Gallate Suppresses Collagen Production and Proliferation in Keloid Fibroblasts via Inhibition of the STAT3-Signaling Pathway. Journal of Investigative Dermatology advance online publication, 8 May 2008; doi:10.1038/jid.2008.103.

Type of study: In vitro

Key finding: Green Tea EGCG suppresses the pathological characteristics of keloids, benign skin tumors, by inhibiting of the STAT3-signaling pathway.

How does it help your skin: Green Tea EGCG may be used to prevent and treat keloids which are mild, non-progressive non-cancerous form of skin tumors.

Keloids are benign skin tumors characterized by collagen accumulation and hyperproliferation of fibroblasts. To find an effective therapy for keloids, we explored the pharmacological potential of (-)-epigallocatechin-3-gallate (EGCG), a widely investigated tumor-preventive agent. When applied to normal and keloid fibroblasts (KFs) in vitro, proliferation and migration of KFs were more strongly suppressed by EGCG than normal fibroblast proliferation and migration (IC(50): 54.4 muM (keloid fibroblast (KF)) versus 63.0 muM (NF)). The level of Smad2/3, signal transducer and activator of transcription-3 (STAT3), and p38 phosphorylation is more enhanced in KFs, and EGCG inhibited phosphorylation of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated protein kinase 1/2 (ERK1/2), and STAT3 (Tyr705 and Ser727). To evaluate the contribution of these pathways to keloid pathology, we treated KFs with specific inhibitors for PI3K, ERK1/2, or STAT3. Although a PI3K inhibitor significantly suppressed proliferation, PI3K and MEK/ERK inhibitors had a minor effect on migration and collagen production. However, a JAK2/STAT3 inhibitor and a STAT3 siRNA strongly suppressed proliferation, migration, and collagen production by KFs. We also found that treatment with EGCG suppressed growth and collagen production in the in vivo keloid model. This study demonstrates that EGCG suppresses the pathological characteristics of keloids through inhibition of the STAT3-signaling pathway. We propose that EGCG has potential in the treatment and prevention of keloids.

Bae JY, Choi JS, Choi YJ, Shin SY, Kang SW, Han SJ, Kang YH. (-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase. Food Chem Toxicol. 2008 Apr;46(4):1298-307.

Type of study: In vivo

Key finding: Green Tea EGCG is able to hinder UV-B-induced collagenolytic MMP production by interfering with the MAPK-responsive pathways.

How does it help your skin: Green Tea EGCG may potentially prevent and treat the cumulative detrimental effects on skin, such as wrinkles or dark spots, that result from long-term exposure to sunlight and especially ultraviolet light.

Ultraviolet (UV) irradiation leads to distinct changes in skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix most likely mediated by matrix metalloproteinases (MMP), collagenases. These changes in collagenous skin tissues have been suggested to be causes of the skin wrinkling observed in premature aging of the skin. This study mimicked the action of environmental ultraviolet on skin and investigated whether (-)epigallocatechin gallate (EGCG), a bioactive catechin component of green tea, mechanistically inhibited activation of MMP-1, MMP-8, and MMP-13 and destruction of collagen in UV-B irradiated human dermal fibroblasts by modulating cellular signaling pathways. Cell viability was moderately decreased by > or = 30% in human dermal fibroblasts treated with 100 mJ/cm2 UV-B, accompanying a substantial generation of reactive oxygen species evidenced by DCF staining. Western blot analysis and immunocytochemical staining revealed that EGCG markedly suppressed collagen degradation enhanced in UV-B-exposed human dermal fibroblast. Pre-treatment of fibroblasts with EGCG also inhibited UV-B-induced production of collagenases, MMP-1, MMP-8 and MMP-13, in a dose-dependent manner. In addition, EGCG rapidly and substantially hampered UV-B irradiation-induced activation of ASK-1 and phosphorylation of MAPK, JNK, p38 MAPK, and ERK1/2, in dermal fibroblasts. These results demonstrate that EGCG has abilities to hamper UV-B-induced collagenolytic MMP production via interfering with the MAPK-responsive pathways. Therefore, EGCG may be a potential agent for the prevention and treatment of skin photoaging.

Chen D, Milacic V, Chen MS, Wan SB, Lam WH, Huo C, Landis-Piwowar KR, Cui QC, Wali A, Chan TH, Dou QP. Tea polyphenols, their biological effects and potential molecular targets. Histol Histopathol. 2008 Apr;23(4):487-96.

Type of study: Review of studies

Key finding: Green Tea EGCG may act to prevent a number of chronic diseases and cancers, but require the identification of more molecular targets and biomarkers for tea polyphenols to improve the design of green tea trials to better understand the mechanisms underlying its anti-cancer activity.

How does it help your skin: Green tea EGCG may act to prevent a number of chronic diseases and cancers, and inhibits tumor incidence.

Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinase-dependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity.

Hsu S, Dickinson D, Borke J, Walsh DS, Wood J, Qin H, Winger J, Pearl H, Schuster G, Bollag WB. Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model. Exp Dermatol. 2007 Aug;16(8):678-84.

Type of study: Animal testing, In vivo

Key finding: Topical application of 0.5% Green Tea EGCG activated pathways which may be potential targets for novel therapeutic approaches to the treatment of some psoriasiform (a dermatosis resembling psoriasis) skin disorders.

How does it help your skin: Green Tea EGCG is may be useful skin in treating some disorders.

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 Sci37 (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 Ther315 (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.

Kwon OS, Han JH, Yoo HG, Chung JH, Cho KH, Eun HC, Kim KH. Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG). Phytomedicine. 2007 Aug;14(7-8):551-5

Type of study: Animal testing, in vitro, in vivo, ex vivo

Key finding: Green Tea EGCG stimulates hair growth through dual proliferative and anti-apoptotic effects on human dermal papilla cells (DPCs).

How does it help your skin: Green Tea EGCG may stimulate hair growth .

Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.

Sevin A, Ozta? P, Senen D, Han U, Karaman C, Tarimci N, Kartal M, Erdo?an B. Effects of polyphenols on skin damage due to ultraviolet A rays: an experimental study on rats. J Eur Acad Dermatol Venereol. 2007 May;21(5):650-6.

Type of study: Animal testing, In vivo

Key finding: Topical application of Green Tea EGCG before UVA exposure decreases sunburn cells and dermo-epidermal activation.

How does it help your skin: Green Tea EGCG prevents and protects the skin from solar ultraviolet radiation exposure when applied topically.

Background: Ultraviolet (UV) radiation causes many acute and chronic conditions such as oedema of the skin, sunburn, immunosuppression, photo-ageing and skin cancer. The use of antioxidants has become of paramount importance in prevention of the damage caused by ultraviolet radiation. Epigallocatechin-3-gallate (EGCG), one of the main components of green tea, has been reported to have anti-inflammatory, antioxidant and anticarcinogenic properties.
Aim: The aim of this experimental study was to investigate to what extent EGCG prevented acute skin damage caused by UVA.
Material and Method: The sample contained 2% EGCG, which was prepared in hydrophilic ointment (USP XXIV) as the vehicle. Twenty-four 12-week-old Wistar albino rats are included in the study and divided into four groups, each containing six rats. Group I was formed to be the control group, which was not applied any topical medication or exposed to UV radiation. Group II was formed to observe acute effects of UVA on the skin, Group III was formed to observe effectiveness of topical EGCG on the skin applied 30 min after exposure to UVA, and Group IV was formed to observe topical EGCG applied 30 min before exposure to UVA. All groups were examined for sunburn cells, leucocyte infiltration, dermo-epidermal activity, collagen changes and elastic fibre pathologies on 24 and 72 h. Statistical analysis was performed using spss 11.5, and chi-squared test was used for the evaluation of parameters.
Results: Group IV showed a statistically significant decrease in sunburn cells and dermo-epidermal activation compared with Group II. Group II showed significant increase in all parameters compared with Group I, showing the effects of UV exposure alone, and no difference was detected in Group II and III.
Conclusion: These results show a protective effect of EGCG when applied topically before UVA exposure. No benefit was detected when EGCG was applied after UV exposure.

Katiyar S, Elmets CA, Katiyar SK. Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair. J Nutr Biochem. 2007 May;18(5):287-96

Type of study: Review of studies

Key finding: Green Tea EGCG offers photoprotective effect against UV carcinogenesis through its chemopreventive actitivity against photocarcinogenesis.

How does it help your skin: Green Tea EGCG when applied topically may protect against ultra violet radiation (UVB) induced skin tumors.

Human skin is constantly exposed to numerous noxious physical, chemical and environmental agents. Some of these agents directly or indirectly adversely affect the skin. Cutaneous overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) has a variety of adverse effects on human health, including the development of melanoma and nonmelanoma skin cancers. Therefore, there is a need to develop measures or strategies, and nutritional components are increasingly being explored for this purpose. The polyphenols present in green tea (Camellia sinensis) have been shown to have numerous health benefits, including protection from UV carcinogenesis. (-)-Epigallocatechin-3-gallate (EGCG) is the major and most photoprotective polyphenolic component of green tea. In this review article, we have discussed the most recent investigations and mechanistic studies that define and support the photoprotective efficacy of green tea polyphenols (GTPs) against UV carcinogenesis. The oral administration of GTPs in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in mice, and this prevention is mediated through: (a) the induction of immunoregulatory cytokine interleukin (IL) 12; (b) IL-12-dependent DNA repair following nucleotide excision repair mechanism; (c) the inhibition of UV-induced immunosuppression through IL-12-dependent DNA repair; (d) the inhibition of angiogenic factors; and (e) the stimulation of cytotoxic T cells in a tumor microenvironment. New mechanistic information strongly supports and explains the chemopreventive activity of GTPs against photocarcinogenesis.

Kundu JK, Surh YJ. Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. Ann N Y Acad Sci. 2007 Jan;1095:504-12.

Type of study: Animal testing, In vivo

Key finding: Green Tea EGCG inhibited tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) induced DNA binding of NF-kappaB and CREB by blocking activation of p38 MAPK, which may provide a molecular basis of cyclooxygenase-2 (COX-2) inhibition by EGCG.

How does it help your skin: Green Tea EGCG may prevent tumors by suppressing tumor promoters.

The modulation of intracellular signaling network involved in an inappropriate expression of cyclooxygenase-2 (COX-2) is a pragmatic approach for chemoprevention with a wide variety of dietary phytochemicals. Epigallocatechin gallate (EGCG), a major green tea polyphenol, is one of the most extensively investigated chemopreventive agents. Our previous study revealed that EGCG inhibited expression of COX-2 and activation of mitogen-activated protein kinases (MAPKs) in mouse skin stimulated with a prototype tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was aimed at identifying transcription factors as molecular targets of EGCG in downregulating COX-2 expression. We found that EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB in mouse skin in vivo. EGCG also suppressed TPA-induced phosphorylation and subsequent degradation of IkappaBalpha, and prevented nuclear translocation of p65. We also examined whether extracellular signal-regulated protein kinase (ERK) and p38 MAPK, which are known to regulate activation of NF-kappaB, can also modulate CREB DNA binding. Pretreatment with U0126 and SB203580, pharmacological inhibitors of ERK and p38 MAPK, respectively, showed that SB203580, but not U0126, attenuated TPA-induced CREB DNA binding in mouse skin. Taken together, EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB by blocking activation of p38 MAPK, which may provide a molecular basis of COX-2 inhibition by EGCG in mouse skin in vivo.

Meeran SM, Mantena SK, Elmets CA, Katiyar SK. (-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interleukin-12-dependent DNA repair. Cancer Res. 2006 May 15;66(10):5512-20.

Type of study: Animal testing, In vivo

Key finding: Topical application of Green Tea EGCG can prevent photocarcinogenesis through an EGCG-induced IL-12-dependent DNA repair mechanism.

How does it help your skin: Topical application of Green Tea EGCG may prevent ultraviolet radiation (UVB) induced tumors.

We have shown previously that topical application of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, prevents photocarcinogenesis in mice. EGCG prevents UVB-induced immunosuppression by inducing interleukin-12 (IL-12). As immunosuppression is a risk factor for photocarcinogenesis, we investigated the possibility that EGCG also prevents UVB-induced photocarcinogenesis through an IL-12-dependent DNA repair mechanism. To investigate this possibility, we determined the effects of EGCG on photocarcinogenesis in IL-12 knockout (KO) mice using the formation of cyclobutane pyrimidine dimers (CPD) as an indicator of the extent of UVB-induced DNA damage. Topical application of EGCG (1 mg/cm(2) skin) prevented photocarcinogenesis in wild-type (C3H/HeN) mice in terms of tumor incidence and tumor multiplicity but did not prevent photocarcinogenesis in IL-12 KO mice. UVB-induced DNA damage, as determined by the formation of CPDs and the number of sunburn cells, was resolved more rapidly in the skin of wild-type mice treated with EGCG than untreated control mice. In contrast, the extent of UVB-induced DNA damage and the numbers of sunburn cells were not significantly different in the EGCG-treated IL-12 KO mice and untreated control mice. In addition, treatment of XPA-proficient human fibroblast cells with EGCG promoted repair of UVB-induced CPDs in a dose-dependent manner but not in an XPA-deficient cells, indicating that the nucleotide excision repair mechanism is involved in EGCG-mediated DNA repair. Taken together, these results indicate for the first time that EGCG can prevent photocarcinogenesis through an EGCG-induced IL-12-dependent DNA repair mechanism.

Song XZ, Bi ZG, Xu AE. Green tea polyphenol epigallocatechin-3-gallate inhibits the expression of nitric oxide synthase and generation of nitric oxide induced by ultraviolet B in HaCaT cells. Chin Med J (Engl). 2006 Feb 20;119(4):282-7.

Type of study: Animal testing, In vivo

Key finding: Green Tea EGCG protects by inhibiting and down regulating the UVB-induced activation of nitric oxide synthase (iNOS) expression and Nitic oxide which are the cause of various inflammatory diseases including sunburn and pigmentation.

How does it help your skin: Green Tea EGCG prevents and protects the skin from ultraviolet B (UVB) irradiation caused sunburn and pigmentation and other inflammatory diseases.

Background: Nitic oxide (NO) has been implicated in the pathogenesis of various inflammatory diseases, including sunburn and pigmentation induced by ultraviolet irradiation. Epigallocatechin-3-gallate (EGCG) is the major effective component in green tea and can protect skin from ultraviolet-induced damage. The purpose of this study was to investigate the protective mechanisms of EGCG on inducible nitric oxide synthase (iNOS) expression and NO generation by ultraviolet B (UVB) irradiation in HaCaT cells.
Methods: HaCaT cells were irradiated with UVB 30 mJ/cm 2 and pretreated with EGCG at varying concentrations. The iNOS mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and NO production was quantified by spectrophotometric method. The expression of NF-kappaB P65 was measured by immunofluorescence cytochemistry staining.
Results: The expression of iNOS mRNA and generation of NO in HaCaT cells were increased by UVB irradiation. EGCG down regulated the UVB-induced iNOS mRNA synthesis and NO generation in a dose dependent manner. The UVB-induced ctivation and translocation of NF-kappaB were also down regulated by EGCG treatment in HaCaT cells (P < 0.01).
Conclusions: Green tea derived-EGCG can inhibit and down regulate the UVB-induced activation and translocation of NF-kappaB, expression of iNOS mRNA and generation of NO respectively, indicating EGCG may play a protective role from UVB-induced skin damage.

Lee JH, Chung JH, Cho KH. The effects of epigallocatechin-3-gallate on extracellular matrix metabolism. J Dermatol Sci. 2005 Dec;40(3):195-204. Epub 2005 Aug 15.

Type of study: Ex vivo

Key finding: Green Tea EGCG can undo the extracellular matrix (ECM) degradation caused by UV radiation even with a topical application of EGCG.

How does it help your skin: Green Tea EGCG may protect against and reverse the cell damaging process from ultraviolet (UV) radiation of the sun.

Background: Anti-oxidants have attracted a lot of interest on account of their function to protect the skin from oxidative stress by ultraviolet (UV) radiation.
Objective: This study examined the effects of epigallocatechin-3-gallate (EGCG), which is a green tea extract, on the extracellular matrix (ECM) changes induced by UV radiation and showed the comparative results with retinoic acid (RA).
Methods: The ECM metabolism is tightly controlled by the collagen degrading matrix metalloprotienases (MMPs) and their tissue inhibitors (TIMPs). Therefore, the expression of MMPs and TIMP-1 was investigated to evaluate the effects of EGCG and RA. Artificial skin was made using three-dimensionally cultured keratinocytes on a collagen matrix populated with fibroblasts. EGCG and RA were added into the medium of the fibroblasts and keratinocytes culture and also applied topically on artificial skins prior to UVA irradiation. The MMPs and TIMP-1 expression levels were measured using Western blot and a zymogram.
Results: EGCG, like RA, decreased the level of MMPs production and increased TIMP-1 expression level. However, EGCG suppressed the activities of the gelatinases and augmented the expressions of the TIMP-1 more than RA did. RA decreased the MMP-1 and MMP-3 expression levels to a greater extent than EGCG. ECM alterations as a result of UVA appeared to be prevented more effectively using the EGCG treatment.
Conclusion: EGCG can reverse the ECM degradation induced by UV even with a topical application of a practical-use concentration. In particular, EGCG proved to be much more effective in ROS-related conditions, such as UVA exposure.

Xia J, Song X, Bi Z, Chu W, Wan Y. UV-induced NF-kappaB activation and expression of IL-6 is attenuated by (-)-epigallocatechin-3-gallate in cultured human keratinocytes in vitro. Int J Mol Med. 2005 Nov;16(5):943-50.

Type of study: In vitro

Key finding: Green Tea EGCG inhibits ultraviolet B (UVB)- and ultraviolet A (UVA)-induced proinflammatory pathway and cell deaths.

How does it help your skin: Green Tea EGCG is a preventive against solar UV-induced skin photoaging and can be added to skin-care or cosmetic products.

Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. UV radiation-induced proinflammatory cytokines mediated by NF-kappaB reportedly play important roles in photoaging and cancer. NF-kappaB and cytokines have been thus perceived as molecular targets for pharmacological intervention. With an increasing amount of knowledge of the actions of green tea extracts at cellular and molecular levels, the beneficial effect of drinking green tea has become well recognized if not completely accepted. The components in green tea have even been added to skin-care products unregulated, while the molecular mechanisms of the actions of those components on human skin are being unraveled. Using cultured human keratinocytes, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent in green tea, on UV-induced activation of transcription factor NF-kappaB and proinflammatory pathway by measuring nuclear translocation of NF-kappaB and IL-6 secretion in vitro. Immunohistochemical and Western blot analysis and ELISA indicated that both nuclear p65 and secreted IL-6 were significantly (p<0.05) induced by UVB (20, 30 mJ/cm2) and UVA irradiation (10, 20 J/cm2). NF-kappaB nuclear translocation and IL-6 secretion induced by UVB and UVA were dramatically inhibited by treatment of EGCG. FACS analysis showed that EGCG also inhibited UVB-induced apoptosis. EGCG recovered UV-induced loss of anti-apoptotic component, bcl-2, and inhibited UV-induced apoptotic component, Fas ligand, expression. Collectively, we conclude that EGCG inhibits UVB- and UVA-induced proinflammatory pathway and inhibits apoptosis in cultured human keratinocytes in vitro. Our data suggest that EGCG be added to cosmetic or skin-care products for prevention from UV-induced skin photoaging if this activity can be further confirmed and no cytotoxicity is reported in human skin in vivo.

Mantena SK, Roy AM, Katiyar SK. Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of angiogenic factors and activation of CD8+ T cells in tumors. Photochem Photobiol. 2005 Sep-Oct;81(5):1174-9.

Type of study: Animal testing, In vivo

Key finding: Topical application of Green Tea EGCG inhibited tumor growth and metastasis in UV-induced tumors, photocarcinogenesis and angiogenic factors while promoting antitumor immune reactivity.

How does it help your skin: Green Tea EGCG may suppress the growth of tumors and promoted anti-tumor reaction.

There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG ( approximately 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.

Balasubramanian S, Sturniolo MT, Dubyak GR, Eckert RL. Human epidermal keratinocytes undergo (-)-epigallocatechin-3-gallate-dependent differentiation but not apoptosis. Carcinogenesis. 2005 Jun;26(6):1100-8. Epub 2005 Feb 17.

Type of study: Ex vivo

Key finding: Green Tea EGCG treatment improves normal keratinocyte (the major cell type of the epidermis) differentiation but does not promote cell deaths.

How does it help your skin: Green Tea EGCG may prevent or slow the development of cancer.

Epigallocatechin-3-gallate (EGCG) is an important chemopreventive agent derived from green tea. We recently reported that EGCG treatment enhances keratinocyte differentiation as evidenced by increased human involucrin promoter activity [Balasubramanian,S., Efimova,T. and Eckert,R.L. (2002) J. Biol. Chem., 277, 1828-1836]. In the present paper, we extend these findings and show that EGCG also increases the expression of other differentiation markers-procaspase 14 and type I transglutaminase (TG1). Both TG1 mRNA and protein level, and activity are increased by treatment with EGCG. Increased TG1 activity is evidenced by a direct transglutaminase assay, and by the ability of EGCG to stimulate the covalent incorporation of fluorescein cadaverine substrate into crosslinked intracellular structures. In contrast, type II transglutaminase levels are not altered by EGCG treatment. We also assessed whether EGCG promotes keratinocyte apoptosis. We show that EGCG treatment does not promote the cleavage of procaspase-3, -8, -9 or poly(ADP-ribose) polymerase. Moreover, treatment with the pan-caspase inhibitor, Z-VAD-FMK, does not reverse the EGCG-associated reduction in cell viability. In addition, there is no increase in cells having sub-G(1)/S DNA content, and no evidence for the release of cytochrome c from the mitochondria. These findings confirm, using several endpoints, that EGCG treatment enhances normal keratinocyte differentiation but does not promote apoptosis.

Nihal M, Ahmad N, Mukhtar H, Wood GS. Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. Int J Cancer. 2005 Apr 20;114(4):513-21.

Type of study: Ex vivo

Key finding: Green Tea EGCG decreases the viability and growth of melanoma cell lines, decreases cell proliferation and causes significant induction of cell cycle arrest and apoptosis of melanoma cells.

How does it help your skin: Green Tea EGCG, alone or together with current therapies, could be useful for the management of melanoma, a type of skin cancer.

Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

Huang CC, Fang JY, Wu WB, Chiang HS, Wei YJ, Hung CF. Protective effects of (-)-epicatechin-3-gallate on UVA-induced damage in HaCaT keratinocytes. Arch Dermatol Res. 2005 Apr;296(10):473-81.

Type of study: Ex vivo

Key finding: L (-)-Epicatechin-3-gallate (ECG), another gallated catechin of Green Tea, ECG is an effective protectant that protects keratinocytes (major cell type of the epidermis) from photodamage.

How does it help your skin: ECG, another constituent of Green Tea like EGCG, may protect the skin from photodamage caused due to exposure to sun.

(-)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been extensively studied and shown to be a powerful antioxidant protecting skin cells against photodamage. In this study, however, we demonstrated that another gallated catechin, (-)-epicatechin-3-gallate (ECG), was also able to protect human keratinocytes against damage induced by ultraviolet A (UVA) light. We found that ECG dose-dependently inhibited UVA-induced keratinocyte death as determined by cell viability assay. Moreover, ECG had similar potency to EGCG in inhibiting UVA-induced cell death. Therefore, the mechanism of action of ECG was further investigated. As assayed by flow cytometry, UVA-induced hydrogen peroxide (H2O2) production in keratinocytes was inhibited by ECG in a concentration-dependent manner, suggesting that ECG can act as a free radical scavenger while keratinocytes were photodamaged. The scavenging effect of ECG was confirmed by the fact that ECG treatment attenuated cell damage induced by H2O2 and hypoxanthine-xanthine oxidase. In a parallel experiment, UVA-induced activation of extracellular signal-regulated kinase in keratinocytes was blocked by ECG. We provided here the first evidence that ECG is a potent protectant that protects keratinocytes from photodamage. Because ECG is abundant in green tea, we believe that this compound is beneficial for skin care.

Morley N, Clifford T, Salter L, Campbell S, Gould D, Curnow A. The green tea polyphenol (-)-epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation-induced damage. Photodermatol Photoimmunol Photomed. 2005 Feb;21(1):15-22.

Type of study: Ex vivo, in vivo

Key finding: Green Tea EGCG prevents ultraviolet radiation (UVR)-induced DNA damage in cultured human cells and also in human peripheral blood samples.

How does it help your skin: Green Tea EGCG may protect against skin cancer by protecting human cells from ultraviolet-induced DNA damage.

Background: Antioxidant compounds in green tea may be able to protect against skin carcinogenesis and it is of interest to investigate the mechanisms involved. A study was therefore conducted to determine whether the isolated green tea polyphenol (-)-epigallocatechin gallate (EGCG) could prevent ultraviolet radiation (UVR)-induced DNA damage in cultured human cells. This work was then extended to investigate whether drinking green tea could afford any UVR protection to human peripheral blood cells collected after tea ingestion.
Methods: The alkaline comet assay was used to compare the DNA damage induced by UVR in cultured human cells with and without the presence of EGCG. The same assay technique was then employed to assess UVR-induced DNA damage in peripheral leucocytes isolated from 10 adult human volunteers before and after drinking 540 ml of green tea.
Results: Initial trials found that EGCG afforded concentration-dependent photoprotection to cultured human cells with a maximal activity at a culture concentration of 250 microM. The cells types tested (lung fibroblasts, skin fibroblasts and epidermal keratinocytes) demonstrated varying susceptibility to the UVR insult provided. The in vivo trials of green tea also demonstrated a photoprotective effect, with samples of peripheral blood cells taken after green tea consumption showing lower levels of DNA damage than those taken prior to ingestion when exposed to 12 min ultraviolet A (UVA) radiation.
Conclusion: The studies showed that green tea and/or some constituents can offer some protection against UV-induced DNA damage in human cell cultures and also in human peripheral blood samples taken post-tea ingestion.

Paul B, Hayes CS, Kim A, Athar M, Gilmour SK. Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice. Carcinogenesis. 2005 Jan;26(1):119-24. Epub 2004 Sep 16.

Type of study: Animal testing

Key finding: Green Tea EGCG may be a valuable chemopreventive agent in those with early, pre-neoplastic stages of cancer.

How does it help your skin: Green Tea EGCG may have anti-cancer property.

Tea polyphenolic constituents induce apoptosis in cancer cells but not in normal cells. To study the mechanism of this selective effect, we used the ornithine decarboxylase (ODC)/Ras double transgenic mouse model that develops spontaneous skin tumors due to over-expression of ODC and a v-Ha-ras transgene. Administration of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in the drinking water significantly decreased both tumor number and total tumor burden compared with untreated ODC/Ras mice without decreasing the elevated polyamine levels present in the ODC/Ras mice. EGCG selectively decreased both proliferation and survival of primary cultures of ODC over-expressing transgenic keratinocytes but not keratinocytes from normal littermates nor ras-infected keratinocytes. This decreased survival was due to EGCG-induced apoptosis and not terminal differentiation. Moreover, in skin from EGCG-treated ODC transgenic mice, caspase 3 (active form) was detected only in epidermal cells that possess very high levels of ODC protein. Since most transformed cells and tumor tissue possess higher levels of polyamines compared with normal cells or tissue, our data suggest that the elevated levels of polyamines in tumor cells sensitize them to EGCG-induced apoptosis. These results suggest that EGCG may be an effective chemopreventive agent in individuals with early, pre-neoplastic stages of cancer having higher levels of polyamines

Chung JH, Han JH, Hwang EJ, Seo JY, Cho KH, Kim KH, Youn JI, Eun HC.
Dual mechanisms of green tea extract (EGCG)-induced cell survival in human epidermal keratinocytes. FASEB J. 2003 Oct;17(13):1913-5.

Type of study: In vivo

Key finding: Green Tea EGCG on topical application to human skin promotes the survival of keratinocyte, a major cell type of the epidermis, inhibits the UV-induced apoptosis (cell death) and promotes keratinocyte survival.

How does it help your skin: Green Tea EGCG, when topically applied, may thicken the outer skin layer (epidermis).

Beneficial effects attributed to green tea, such as its anticancer and antioxidant properties, may be mediated by (-)-epigallocatechin-3-gallate (EGCG). In this study, the effects of EGCG on cell proliferation and UV-induced apoptosis were investigated in normal epidermal keratinocytes. When topically applied to aged human skin, EGCG stimulated the proliferation of epidermal keratinocytes, which increased the epidermal thickness. In addition, this topical application also inhibited the UV-induced apoptosis of epidermal keratinocytes. EGCG was found to increase the phosphorylation of Bad protein at the Ser112 and Ser136. Moreover, EGCG-induced Erk phosphorylation was found to be critical for the phosphorylation of Ser112 in Bad protein, and the EGCG-induced activation of the Akt pathway was found to be involved in the phosphorylation of Ser136. Furthermore, EGCG increased Bcl-2 expression but decreased Bax expression, causing an increase in the Bcl-2-to-Bax ratio. In addition, we demonstrate the differential growth inhibitory effects of EGCG on cancer cells. In conclusion, this study demonstrates that EGCG promotes keratinocyte survival and inhibits the UV-induced apoptosis via two mechanisms: by phosphorylating Ser112 and Ser136 of Bad protein through Erk and Akt pathways, respectively, and by increasing the Bcl-2-to-Bax ratio. Moreover, these two proposed mechanisms of EGCG-induced cell proliferation may differ kinetically to promote keratinocyte survival.

Katiyar SK. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42.

Type of study: In vitro and in vivo, human trial

Key finding: Topical application or oral consumption of Green Tea EGCG are photoprotective; inhibit chemical carcinogen- or UV radiation-induced skin carcinogenesis, erythema, oxidative stress and infiltration of inflammatory leukocytes; prevents UVB-induced inflammatory responses, immunosuppression, oxidative stress and cyclobutane pyrimidine dimers formation; and protects against UVB-induced local as well as systemic immune suppression.

How does it help your skin: Green Tea EGCG may help prevent UVB light-induced skin disorders including melanoma and nonmelanoma skin cancers, and photoaging.

Because of a characteristic aroma and health benefits, green tea is consumed worldwide as a popular beverage. The epicatechin derivatives, commonly called polyphenols, present in green tea possess antioxidant, anti-inflammatory and anti-carcinogenic properties. The major and most highly chemopreventive constituent in green tea responsible for the biochemical or pharmacological effects is (-)-epigallocatechin-3-gallate (EGCG). Epidemiological, clinical and biological studies have implicated that solar ultraviolet (UV) light is a complete carcinogen and repeated exposure can lead to the development of various skin disorders including melanoma and nonmelanoma skin cancers. We and others have shown that topical treatment or oral consumption of green tea polyphenols (GTP) inhibit chemical carcinogen- or UV radiation-induced skin carcinogenesis in different laboratory animal models. Topical treatment of GTP and EGCG or oral consumption of GTP resulted in prevention of UVB-induced inflammatory responses, immunosuppression and oxidative stress, which are the biomarkers of several skin disease states. Topical application of GTP and EGCG prior to exposure of UVB protects against UVB-induced local as well as systemic immune suppression in laboratory animals, which was associated with the inhibition of UVB-induced infiltration of inflammatory leukocytes. Prevention of UVB-induced suppression of immune responses by EGCG was also associated with the reduction in immunosuppressive cytokine interleukin (IL)-10 production at UV irradiated skin and draining lymph nodes, whereas IL-12 production was significantly enhanced in draining lymph nodes. Antioxidant and anti-inflammatory effects of green tea were also observed in human skin. Treatment of EGCG to human skin resulted in the inhibition of UVB-induced erythema, oxidative stress and infiltration of inflammatory leukocytes. We also showed that treatment of GTP to human skin prevents UVB-induced cyclobutane pyrimidine dimers formation, which are considered to be mediators of UVB-induced immune suppression and skin cancer induction. The in vitro and in vivo animal and human studies suggest that green tea polyphenols are photoprotective in nature, and can be used as pharmacological agents for the prevention of solar UVB light-induced skin disorders including photoaging, melanoma and nonmelanoma skin cancers after more clinical trials in humans.

Hsu S, Bollag WB, Lewis J, Huang Q, Singh B, Sharawy M, Yamamoto T, Schuster G. Green tea polyphenols induce differentiation and proliferation in epidermal keratinocytes. J Pharmacol Exp Ther. 2003 Jul;306(1):29-34.

Type of study: Ex vivo

Key finding: Green Tea EGCG brought forth cell differentiation, renewed DNA synthesis, and activated succinate dehydrogenase indicating potential use in skin conditions with altered cellular metabolism or activities.

How does it help your skin: Green Tea EGCG may be used to treat wounds and other skin conditions.

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 transglutaminase 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.

Vayalil PK, Elmets CA, Katiyar SK. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin. Carcinogenesis. 2003 May;24(5):927-36.

Type of study: Animal testing, In vivo

Key finding: Topical treatment with Green Tea EGCG prevented ultraviolet B-induced depletion of antioxidant enzymes, and inhibited ultraviolet B-induced oxidative stress.

How does it help your skin: Green Tea EGCG may protects the skin from solar ultraviolet B induced oxidative stress mediated skin disorders.

The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P < 0.005-0.001), catalase (51-92%, P < 0.001) and glutathione level (87-100%, P < 0.005). Treatment of EGCG or GTP also inhibited UVB-induced oxidative stress when measured in terms of lipid peroxidation (76-95%, P < 0.001), and protein oxidation (67-75%, P > 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P < 0.01-0.001), oxidative stress (33-71%, P < 0.01) and phosphorylation of ERK1/2, JNK and p38 proteins of MAPK family but the photoprotective efficacy was comparatively less than that of topical treatments of EGCG and GTP. Lesser photoprotective efficacy of GTP in d.w. in comparison with topical application may be due to its less bioavailability in skin target cells. Together, for the first time a cream based formulation of green tea polyphenols was tested in this study to explore the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans.

Afaq F, Adhami VM, Ahmad N, Mukhtar H. Inhibition of ultraviolet B-mediated activation of nuclear factor kappaB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate. Oncogene. 2003 Feb 20;22(7):1035-44.

Type of study: Ex vivo

Key finding: Green Tea EGCG inhibits ultraviolet B-mediated degradation and protects against adverse effects of UV radiation through the modulations in NF-kappaB pathway indicating the photochemopreventive effect of EGCG

How does it help your skin: Green Tea EGCG may offer protection against the adverse effects of solar UV radiation on the skin, particularly skin cancer.

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, possesses significant anti-inflammatory and cancer chemopreventive properties. Studies have shown the photochemopreventive effects of green tea and EGCG in cell culture, animal models, and human skin. The molecular mechanism(s) of photochemopreventive effects of EGCG are incompletely understood. We recently showed that EGCG treatment of the normal human epidermal keratinocytes (NHEK) inhibits ultraviolet (UV)B-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we evaluated the effect of EGCG on UVB-mediated modulation of the nuclear factor kappa B (NF-kappaB) pathway, which is known to play a critical role in a variety of physiological functions and is involved in inflammation and development of cancer. Immunoblot analysis demonstrated that the treatment of NHEK with EGCG (10-40 microM) for 24 h resulted in a significant inhibition of UVB (40 mJ/cm(2))-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha, in a dose-dependent manner. UVB-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha was also observed in a time-dependent protocol (15 and 30 min, 1, 2, 3, 6, 12 h post-UVB exposure). Employing immunoblot analysis, enzyme-linked immunosorbent assay, and gel shift assay, we demonstrate that EGCG treatment of the cells resulted in a significant dose- and time-dependent inhibition of UVB-mediated activation and nuclear translocation of a NF-kappaB/p65. Our data suggest that EGCG protects against the adverse effects of UV radiation via modulations in NF-kappaB pathway, and provide a molecular basis for the photochemopreventive effect of EGCG.

Fujiki H, Suganuma M, Kurusu M, Okabe S, Imayoshi Y, Taniguchi S, Yoshida T. New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen. Mutat Res. 2003 Feb-Mar;523-524:119-25.

Type of study: Review of studies

Key finding: Studies on potential cancer preventive agents in herbal medicines indicate that Green Tea EGCG along with sulindac or tamoxifen shows high inhibitory potential against cancer.

How does it help your skin: Green Tea EGCG may have anti-cancerous property.

Herbal medicines are now attracting attention as potential sources of cancer preventive agents. Using inhibition of tumor necrosis factor-alpha (TNF-alpha) release assay, we studied Acer nikoense, Megusurino-ki in Japanese. Inhibitory potential was found in the leaf extract, and the main active principles were identified as geraniin and corilagin. The IC(50) values for TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG), the green tea polyphenol, as control was 26 microM. Furthermore, treatment with geraniin inhibited okadaic acid tumor promotion in a two-stage carcinogenesis experiment on mouse skin. Geraniin and corilagin are present in another well-known Japanese traditional herb, Geranium thunbergii, Genno-shoko in Japanese. Considering seasonal variations of the agents and sites of cultivation of herbs, this paper reviews the significance of geraniin as a new cancer preventive agent. In addition, based on accumulated results of green tea as a cancer preventive, we review two important results with EGCG: the synergistic effects of EGCG with sulindac or tamoxifen on cancer preventive activity in PC-9 cells, and cancer prevention of intestinal tumor development in multiple intestinal neoplasia (Min) mice by cotreatment using EGCG with sulindac. We report here new findings on additional gene expression resulting from cotreatment with EGCG and sulindac in PC-9 cells compared with gene expression by EGCG alone or sulindac alone. Overall, our results indicate that, with the continuing spread of cancer chemoprevention as a fundamental medical strategy, both clinicians and researchers should take a closer look at herbal medicine.?

Green Tea EGCG

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BulkActives are DIY skin care suppliers of skin actives, cosmetic ingredients, cosmeceuticals, active ingredients, and standardized botanical extracts for diy skin care products and homemade cosmetics.

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