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Role of Coffea arabica Extract and Related Compounds in Preventing Photoaging and Photodamage of the Skin
C H A P T E R
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Role of Coffea arabica Extract and Related Compounds in Preventing Photoaging and Photodamage of the Skin Hsiu-Mei Chiang, Chien-Wen Chen, Chien-Chia Chen, Hsiao-Wen Wang, Jhe-Hua Jhang, Ya-Han Huang, Kuo-Ching Wen Department of Cosmeceutics, China Medical University, Taichung, Taiwan
List of Abbreviations
photoaging and skin cancer risk,4,5 has recently drawn a considerable amount of interest. Natural products possessing anti-inflammatory, immunomodulatory, and antioxidant properties have been exploited as ideal chemopreventive agents for various skin disorders. In addition, bench works and epidemiological studies have provided evidence supporting the use of certain botanical ingredients, such as coffee berries and leaves, and the findings regarding the proposed biological mechanisms have been applied in the cosmetics industry.4
AQP-3 Aquaglycerolporins-3 ECM Extracellular matrix GAGs Glycosaminoglycans GM-CSF Granulocyte-macrophage colony-stimulating factor MAPK Mitogen-activated protein kinase MMP Matrix metalloproteinase NMFs Natural moisturizing factors ROS Reactive oxygen species TGF-β1 Transforming growth factor-β1 UV Ultraviolet
58.1 INTRODUCTION
58.2 AGING AND PHOTOAGING
Coffee is one of the most popular drinks worldwide. Coffee consumption, a major source of dietary antioxidants, inhibits inflammation and therefore reduces the risk of cardiovascular disease and other inflammatory diseases in postmenopausal women.1 Coffee extract scavenges superoxide free radicals and inhibits lipid peroxidation, hepatitis B virus expression, and enterobacteria growth. Coffee is a complex mixture of chemicals, and the components of Coffea arabica are diterpenoid alcohols (such as cafestol and kahweol), an alkaloid (caffeine), and phenolic acids (caffeic acid and chlorogenic acid)2 (Figure 58.1). Coffee contains an abundance of polyphenols and phenolic acids, including chlorogenic acids, caffeoylquinic acids, feruloylquinic acids, dicaffeoylquinic acids, p-coumaroylquinic acids, caffeic acid, ferulic acid, and their derivatives.2,3 Using natural products for preventing ultraviolet (UV)-irradiation-induced photodamage, including
Skin aging is a progressive process that can be divided into intrinsic and extrinsic aging.6 UV irradiation is the major cause of extrinsic aging; extrinsic aging caused by UV irradiation is called photoaging. Intrinsic aging is characterized by smooth, dry, pale, and finely wrinkled skin, whereas photoaged skin is characterized by rough, fine, coarse wrinkling and mottled hyperpigmentation on exposed areas such as the face, neck, and forearms. UV irradiation from sunlight is a potent factor in skin photoaging and photocarcinogenesis. UV irradiation generates mutagenic and carcinogenic chemical compounds that cause DNA damage (e.g., [6,4]pyrimidinepyrimidone photoproducts and cyclobutane pyrimidine dimers).7 The incidence of sunlight-induced skin cancer is increasing because of increased recreational sun exposure, the use of UV tanning beds, and the deterioration of the ozone layer. Epidemiological, clinical, and laboratory studies have indicated that solar UV irradiation is a complete carcinogen and that excessive exposure
Coffee in Health and Disease Prevention http://dx.doi.org/10.1016/B978-0-12-409517-5.00058-9
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© 2015 Elsevier Inc. All rights reserved.
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58. COFFEE IN PHOTOAGING DAMAGE
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FIGURE 58.1 Structures of caffeine (A), caffeic acid (B), and chlorogenic acid (C).
can lead to the development of various skin disorders including melanoma and nonmelanoma skin cancers.7
58.3 MECHANISMS OF PHOTOAGING UV-irradiation-induced inflammation and the resulting accumulation of reactive oxygen species (ROS) has been reported to play a crucial role in chronologically aged and photoaged skin in vivo.5,8 Increased ROS production alters gene and protein structure and function, which leads to skin damage.6 UV irradiation also enhances collagenase activity and contributes to wrinkle formation through collagen degradation in the dermal extracellular matrix (ECM).6 UVB irradiation induces ROS production, which promotes downstream signal transduction in the dermis, causing skin damage and photoaging (Figure 58.2). UV irradiation induces the synthesis of matrix metalloproteinases (MMPs) in human skin in vivo. UVB is known to induce the overexpression of MMP-1, -3, and -9 in the normal human epidermis in vivo.5,8,9 MMP-1 initiates the degradation of type I and type III fibrillar collagens, MMP-3 activates proMMP-1, and MMP-9 further
degrades the collagen fragments generated by collagenases.5,6 UV irradiation induces the overexpression of MMPs, degrading proteins in the ECM, including collagen and elastin, and leading to the formation of coarse wrinkles and sagging skin. UV irradiation reduces the production of collagen, which is the major component of the dermis, and causes an imbalance between MMPs synthesis and degradation6 (Figure 58.2). The ECM functions as the skin skeleton in the dermis. The most abundant structural protein in skin connective tissue is type I collagen, which is responsible for contributing strength and resiliency.6,7 The degradation of collagen and elastin caused by intrinsic aging causes the loss of elasticity, sagging, stretch marks, and fine wrinkling observed in the skin. Type I collagen is synthesized as a soluble precursor, and type I procollagen is secreted by fibroblasts and proteolytically processed to form insoluble collagen fibers. In addition to collagen, elastin also contributes to skin plasticity. Collagens and elastin form a three-dimensional network that constitutes the architectural basis of the dermis and are involved in skin integrity, suppleness, and plasticity. UV irradiation enhances the secretion of elastase and degrades elastin, causing sagging of the skin.6 Disorganization, fragmentation, and dispersion of collagen bundles are prominent features of photodamaged human skin. Numerous studies have proposed that MMP-mediated collagen destruction is largely responsible for the connective tissue damage that occurs in photoaging.6 Mitogen-activated protein kinase (MAPK) activation is a photoaging pathway and a factor in MMP production in fibroblasts. c-Jun NH2-teeminal kinase (JNK) and p38 modulate c-Fos expression, and c-Fos, accompanied by c-Jun, synthesizes the transcription factor activator protein-1 (AP-1). Inhibiting extracellular signalregulated kinase (ERK), JNK, and p38 expression may suppress c-Fos and c-Jun expression and inhibit AP-1, MMP, and type I procollagen expression. Transforming growth factor (TGF)-β1 and granulocyte-macrophage colony-stimulating factor are involved in numerous aspects of connective tissue repair; they play a vital role in regulating cell growth, differentiation, biosynthesis, and the deposition of ECM compounds by fibroblasts. TGF-β1 is essential for dermal strength and is partially responsible for the contraction of the dermis. TGF-β1 activates the production of collagen, fibronectin, glycosaminoglycans, and elastin by fibroblasts and is the most powerful known stimulator of collagen synthesis.10 Hydration of the stratum corneum determines the appearance and physical properties of the skin. Skin structure, lipid and protein composition, barrier function, and natural moisturizing factors, such as free amino acids, pyrrolidone carboxylic acid, and lactate, influence skin hydration. Aquaglycerolporin-3, the water- and glycerol-transporting proteins in keratinocytes, reduce stratum corneum hydration and skin elasticity.11 These
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58.5 Coffee Prevents Skin Photoaging
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FIGURE 58.2 Mechanism of ultraviolet (UV)-irradiationinduced photoaging. AP-1, activating protein-1; ECM, extracellular matrix; MMPs, matrix metalloproteinase; ROS, reactive oxygen species.
proteins play vital roles in skin hydration and barrier function, thus preventing water loss. UV-irradiation-induced DNA damage also induces multiple signal transduction networks that coordinate cell cycle checkpoint arrest and induced apoptosis. Another vital pathway activated in response to UV irradiation is the phosphoinositol-3-kinase-like ataxia telangiectasia and Rad3-related protein kinase (ATR). UV irradiation reduces the level of cyclin B1 and messenger RNA (mRNA), preventing entry into mitosis by both an ataxia-telangiectasia mutated (ATM)– and ATR-dependent mechanism and an ATM- and ATR-independent mechanism.12 The UVBactivated ATR pathway causes phospho-checkpoint kinase 1 (Chk1)-(Ser345) to increase in keratinocytes and a marked decrease cyclin B1 in mitotic keratinocytes.12
58.4 ANTIOXIDANT ACTIVITY OF COFFEE Oxidative damage by ROS plays a major role in aging, photoaging, and carcinogenesis.7 Previous studies have reported that the phenolic content of plants contributes to antioxidant activity. Coffee and coffee berry extracts are rich in polyphenols, which are known to have a strong antioxidant effect.4 UVB irradiation induces ROS production and promotes downstream signal transduction in the dermis, causing skin damage and photoaging. Thus, inhibiting ROS production prevents the skin from photoaging. Coffee berry extract exhibits antioxidant activity mediated by potent antioxidant polyphenols, especially chlorogenic acid, proanthocyanidins, quinic acid, and ferulic acid.13 The extract of C. arabica leaves has shown significant 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and protection for 2,2’-Azobis(2-amidinopropane)
dihydrochloride (AAPH)-induced erythrocyte hemolysis.9 The extract of C. arabica leaves also inhibits UVBirradiation-induced intracellular ROS generation in human skin fibroblasts and against UVB-irradiationinhibited catalase activity, but not glutathione, in human skin fibroblasts (unpublished data). Green coffee oil also has demonstrated antioxidant ability; therefore, it prevents the deleterious actions of free radicals1 and increases ECM synthesis by scavenging free radicals.14 Low (0.01 mM) and intermediate (0.1 mM) doses of caffeine, the major constituent of coffee, protect human skin fibroblasts from hydrogen peroxide-induced cell damage.15 These studies have indicated that coffee is a potential candidate for preventing aging and photoaging.
58.5 COFFEE PREVENTS SKIN PHOTOAGING In a clinical study, patients exhibiting actinic damage of the skin used a skin care system containing Coffeeberry® extract.13 Compared with a placebo, the test cream was superior in improving fine lines, wrinkles, pigmentation, and overall appearance.13 Orally administering and topically applying antioxidant plant extracts, such as coffee extract, can protect skin from UV-irradiationinduced erythema, early aging, and irradiation-induced cancer. Studies have reported that coffee consumption is not associated with the grade of elastosis,16 facial wrinkle formation,17 and skin characteristics.18 Treating human cultured fibroblasts with Coffeeberry® showed that gene expression of several collagens and a connective tissue growth factor was upregulated and that gene expression of MMPs was downregulated.13 Coffea arabica extract-stimulated type I procollagen expression, inhibited MMP-1, -3, and -9 expression
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and inhibited the phosphorylation of JNK, ERK, and p38.9 These results show that C. arabica extract can repair photodamage in skin and increase skin barrier function through inhibiting MMP expression and the MAPK pathway (JNK, ERK, and p38).9 C. arabica extract inhibits MAPK phosphorylation and modulates c-Fos expression. Finally, a report indicated that topical products that include C. arabica or coffee berry extract are considered safe.13 Green coffee oil stimulated the synthesis of proteins in the ECM, including collagen, elastin, and glycosaminoglycans. In addition, it increased the release of TGF-β1 and granulocyte-macrophage colony-stimulating factor in normal human dermal fibroblasts.14 It also induced the expression of aquaglycerolporin-3 mRNA in normal human dermal fibroblasts to prevent water loss in the dermis, and it might improve physiological balance in the skin.14
58.6 COFFEE PREVENTS SKIN TUMOR FORMATION In epidemiological studies, daily intake of caffeinecontaining coffee reduces the incidence of skin cancers such as nonmelanoma skin cancer. Daily caffeinated coffee consumption was associated with a dose-related, reduced prevalence of nonmelanoma skin cancer in Caucasian women. Women who drink caffeinated coffee on a daily basis had a 10.8% lower prevalence of nonmelanoma skin cancer, and six or more cups per day was associated with a 36% reduction in nonmelanoma skin cancer. However, in contrast to caffeinated coffee, daily consumption of decaffeinated coffee was not associated with a substantial change in self-reported nonmelanoma skin cancer. Each additional cup of caffeinated coffee ingested was associated with a 5% decrease in the risk of developing nonmelanoma skin cancer, whereas drinking decaffeinated coffee showed no such association.19 In another study, coffee consumption was not associated with cutaneous malignant melanoma risk20 and basal cell carcinoma.21 However, one study indicated that drinking coffee substantially reduces cutaneous malignant melanoma risk in women but not in men.22 Coffee consumption studies related to human skin disorders are summarized in Table 58.1. According to animal studies, orally administering a caffeine solution inhibits UVB-irradiation-induced complete carcinogenesis in SKH-1 mice. Orally administering coffee or a caffeine solution for 2 weeks enhanced UVB-irradiation-induced increases in apoptosis in the epidermis, but these treatments had no effect in the non-UVB-treated normal epidermis. Administering coffee and caffeine may inhibit UVB-irradiation-induced carcinogenesis by enhancing UVB-induced apoptosis.23
TABLE 58.1 Epidemiologic Studies of the Effect of Coffee Consumption on Photoaging and Skin Cancer Subjects
Results
References
Norwegian men and Reduced risk of cutaneous 22 women malignant melanoma in women but not in men Caucasian women
Dose-related decreased prevalence of nonmelanoma skin cancer
19
Healthy individuals
No influence on the results of skin impedance spectroscopic measurements
18
Mediterranean population
No influence on skin aging and wrinkle formation
16,17
Basal cell carcinoma, Reduced basal cell carcinoma squamous cell risk but not risk of squamous carcinoma, and cell carcinoma and melanoma melanoma cases
45
Long-term (20-week) topical application of caffeine to mice previously treated with UVB irradiation inhibited tumor formation and stimulated apoptosis in tumor cells.
58.7 EFFECT OF COFFEE CONSTITUENTS ON PHOTOAGING AND PHOTOCARCINOGENESIS Coffee is a complex mixture of chemicals and contains substantial amounts of caffeine, chlorogenic acid, and other phenolic acids. Chlorogenic acid, caffeic acid, and caffeine, which contribute to the potential of C. arabica to effectively prevent photoaging. Studies of the role of coffee constituents in protecting skin from UV irradiation are summarized in Tables 58.2–58.4.
58.7.1 Caffeine Caffeine is a key component in numerous popular drinks, especially tea and coffee. Caffeine is increasingly used in cosmetics because of its high biological activity and ability to penetrate the skin barrier.4,38 Tissue fat secretes antiapoptotic adipokines that have a tumor-promoting effect. Caffeine stimulates the degradation of fats by inhibiting phosphodiesterase activity and is popularly used as an active compound in anticellulite products that may contribute to anticarcinogenic activity.39 Caffeine also exhibits potent antioxidant properties and inhibits lipid peroxidation. It helps protect cells from UV irradiation and slows the process of photoaging and carcinogenesis of the skin.38,39 Increasing molecular, cellular, and epidemiological evidence suggests that caffeine
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58.7 Effect of Coffee Constituents on Photoaging and Photocarcinogenesis
TABLE 58.2 The Activities of Caffeine in Skin Cells and Animal Studies Materials
Model
Results
References
Caffeine
Primary human keratinocytes
Inhibited ATR-Chk1
24
Human keratinocytes (HaCaT)
Blocked UVB-induced Chk1 and AKT phosphorylation Upregulated COX-2 Promoted apoptosis
25
Human lymphocytes
Reduced 5-methoxypsolaren-induced phototoxicity
46
Human skin fibroblasts
Antioxidant Inhibited H2O2-generated free radicals and 4-hydroxy-2-nonenal
47
JB6 Cl41 cells
Induced phosphorylation of p53 Elevated bax expression Increased cleavaged caspase-3
26
JB6 Cl41 cells
Suppressed cell cycle progression at the G0/G1 phase Inhibited phosphorylation of retinoblastoma protein at Ser780 and Ser807/Ser811 inhibited the activation of the cyclin D1-cdk4 complex
27
SKH-1 hairless mice
Inhibited tumor formation and growth
48
SKH-1 hairless mice
Decreased UVB-induced keratoacanthomas and squamous cell carcinomas
28
SKH-1 hairless mice
Decreased UVB-induced phospho-Chk1 (Ser317) Increased mitotic cells with cyclin B1 and caspase-3 Enhanced UVB-induced apoptosis in epidermis
29
SKH-1 hairless mice
Promoted the deletion of DNA-damaged keratinocytes
30
SKH-1 hairless mice
Decrease UVB-induced nonmalignant and malignant skin tumors
49
SKH-1 hairless mice
Decreased UVB-induced thymine dimers Inhibited UVB-induced sunburn skin lesions
31
Oral caffeine
Topical caffeine
Dermabase cream containing caffeine
Chk1, checkpoint kinase 1; COX-2, cyclooxygenase 2; H2O2, hydrogen peroxide; UV, ultraviolet.
TABLE 58.3 Activities of Caffeic Acid in Skin Cells and Animal Studies Material
Model
Results
Reference
Caffeic acid
BALB/cBYJ mice
Inhibited UVB-induced interleukin-10 expression and mitogen-activated protein kinase
32
Caffeic acid
Human keratinocytes (HaCaT)
Inhibited UVA-induced cytotoxicity Induced MMP-1 activity and mRNA Upregulated antioxidant system
33
Caffeic acid
Mouse skin epidermal (JB6) cells
Suppressed UVB-induced COX-2 expression and prostaglandin E2 Suppressed UVB-induced skin carcinogenesis by inhibiting Fyn kinase activity
34
Caffeic acid (topical)
Human skin
Reduced UVB-induced erythema
35
COX-2, cyclooxygenase 2; MMP, matrix metalloproteinase; mRNA, messenger RNA; UV, ultraviolet.
may have a substantial protective effect against UV-irradiation-induced carcinogenesis in mice and humans.19 Caffeine selectively induces apoptosis in UV-damaged keratinocytes but not in undamaged areas.23 Caffeine inhibits ATR and ATM kinases, both of which are central components of the DNA damage response.40 Following UVB irradiation, caffeine also induces an apoptotic response through caspase-3 and
poly(ADP-ribose) polymerase cleavage,24,29,41 reduces phospho-Chk1 (Ser317), and increases cyclin B1 in mitotic cells.29 Topically applying caffeine inhibits carcinogenesis and promotes apoptosis in the sunburned cells of UVB-pretreated hairless SKH-1 mice. Moreover, UV-irradiation-induced skin roughness and transverse rhytids in mice decreased when caffeine was topically applied after exposure to UV light.30
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TABLE 58.4 Activities of Chlorogenic Acid in Skin Cells and Animal Studies Material
Model
Results
Reference
Chlorogenic acid
Human skin fibroblasts
Inhibited MMP-3 9 Did not restore UVB-induced type 1 procollagen damage
Rats
Antioxidant Increased cell proliferation
36
Guinea pig skin
Prevented UVinduced erythema
37
MMP, matrix metalloproteinase; UV, ultraviolet.
Orally administering caffeine to mice markedly inhibited UVB-irradiation-induced Chk1 phosphorylation on serine 345 in the epidermis, indicating that the ATRChk1 pathway can be inhibited in the target tissue by administering caffeine.40 Topically applying caffeine to mice enhanced p53-mutated cells eliminated from skin keratinocytes, indicating that caffeine may prevent UVirradiation-induced skin cancer development. In addition, p53 is not required to produce the effect of caffeine because p53-mutant patches of keratinocytes were selectively killed when caffeine was topically applied.42 A potential mechanism of the inhibitory effect of caffeine is induced apoptosis in keratinocytes damaged by UV irradiation. Even long after UV exposure was complete, the topical application of caffeine selectively induced apoptosis in nonmalignant tumors and squamous cell carcinomas without affecting neighboring “normal” nontumorous skin in mice.23 SKH-1 hairless mice were irradiated with UVB twice weekly for 20 weeks. These tumor-free mice then were treated topically with caffeine once each day, 5 days/ week, for 18 weeks but were not treated with UVB. Topical applications of caffeine to these mice reduced the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively.23 In addition to the stimulatory effect of caffeine on UVB-irradiationinduced apoptosis in the epidermis23,43 and apoptosis in tumors,23 caffeine also exhibited a sunscreen effect.31 Caffeine has a selective apoptotic effect in UVB- irradiation-induced DNA damage in the epidermis and in tumors but does not cause apoptosis in normal epidermis or in nontumor areas adjacent to tumors.23 Caffeine promoted apoptosis in primary human keratinocytes by inhibiting the ATR-Chk1 pathway. Activation of the ATR-Chk1 pathway normally results in cell cycle checkpoint activation. Applying an ATR pathway inhibitor such as caffeine may protect the skin from UVB irradiation by augmenting the apoptotic elimination of UVBdamaged keratinocytes independent of the status of p53. Mechanistic studies indicate that caffeine administration
enhances UVB-irradiation-induced apoptosis in the mouse epidermis by increasing wild-type p5323 and through a p53- and bax-independent mechanism.43 Studies of a p53-independent mechanism suggest that caffeine may enhance UVB-irradiation-induced apoptosis by inhibiting the ATR-mediated phosphorylation of Chk1, increasing the level of cyclin B1 and abrogating the UVB-irradiation-induced blockage at the G2 checkpoint, thereby resulting in lethal mitosis.23 Caffeine effectively inhibits the UVB-induced AKT/cyclooxygenase-2 (COX-2) pathway independent of the ATR kinase and blocks AKT/COX-2 signaling by specifically eliminating UVB-irradiation-damaged keratinocytes without complete DNA repair through apoptosis.25 In another study, low concentrations of caffeine induced apoptosis in JB6 Cl41 cells. The cells showed the typical DNA laddering pattern and other characteristics of apoptosis.26 The IC50 of caffeine on JB6 Cl41 cells was 2.7 mM. The apoptosis that was induced by caffeine seemed to be p53-dependent because cells lacking p53 (p53(−/−)) showed no signs of apoptosis after treatment with caffeine. Caffeine induced the phosphorylation of p53 at Ser-15 in JB6 Cl41 cells, increased p53 activation and the expression of Bax, and cleaved caspase-3.26 The results indicated that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase-3 pathways.26 Caffeine inhibited cell growth and signal-induced activation of cdk4, thereby suppressing the progression of quiescent cells in the cell cycle in the mouse epidermal cell line (JB6 cell).27 Caffeine may prevent the DNA-damaging effect of UVB on skin.
58.7.2 Chlorogenic Acid Chlorogenic acid inhibits MMP-3 expression, but not expression of MMP-1 and MMP-9, and does not restore UVB-irradiation-induced type I procollagen damage.9 However, chlorogenic acid has been reported to inhibit the MMP-9 activity of the hepatocellular carcinoma cell line (Hep3B). Pretreating JB6 cells with chlorogenic acid blocked UVB-irradiation- or 12-o-tetradecanoylphorbol13-acetate (TPA)-induced transactivation of AP-1 and nuclear factor-κB, and chlorogenic acid reduced the phosphorylation of JNK, p38 kinase, and ERK induced by UVB or TPA.44 Pretreating guinea pig dorsal skin with chlorogenic acid containing microemulsion gel prevented erythema formation induced by UV irradiation.37 Chlorogenic acid also was reported to inhibit the TPA-dependent stimulation of DNA synthesis and reduce the number of tumors.28 Chlorogenic acid exhibited potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione and reducing lipid peroxidation in rats. Chlorogenic acid improved cellular proliferation and increased epithelialization rates. It also increased
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References
tumor necrosis factor-α levels during the inflammatory phase of wound healing, upregulated TGF-β1, and enhanced collagen IV synthesis. Topically applying chlorogenic acid accelerates the process of excision wound healing.36
58.7.3 Caffeic Acid Caffeic acid, a phenolic acid present in numerous dietary plants, was shown to exhibit antioxidant, antiinflammatory, and anticancer activities. Caffeic acid inhibited UVB-irradiation-induced overexpression of MMP-1 and -9, but not of MMP-3, in human skin fibroblasts.9 In addition, caffeic acid did not prevent UVBirradiation-induced type I procollagen degradation.9 In a previous study, caffeic acid applied on abdominal skin suppressed UVA-irradiation-induced ROS; caffeic acid existed in the skin after oral ingestion. Caffeic acid pretreatment reduced the cytotoxicity of the HaCaT after UVA irradiation33 and suppressed UVA- irradiationinduced MMP-1 activity and mRNA oxidant formation. Caffeic acid also upregulated glutathione content, mRNA of γ-glutamate cysteine ligase and its activities, and mRNA expression of catalase and glutathione peroxidase in UVA-irradiated cells. Therefore, caffeic acid produced protective effects on UVA-irradiation-mediated MMP-1 induction in HaCaT cells, possibly because it restores the antioxidant defense system at the cellular and molecular levels.33 In addition, caffeic acid showed weak collagenolytic activity. Topically applying caffeic acid protected the skin from UVB-irradiation-induced erythema.35 In vitro and in vivo experiments demonstrated that caffeic acid may be successfully used as a topical protective agent against UV-irradiation-induced skin damage.35 Caffeic acid attenuates the local immune suppression induced by UVB irradiation and inhibits the transcriptional activation of the UVB-irradiation-induced interleukin (IL)-10 promoter, IL-10 mRNA expression, and protein production in mouse skin.32 Caffeic acid might inhibit IL-10 production by interfering with prostaglandin E2 synthesis, which is involved in activating the UVB-irradiation-induced immune suppressive cytokine cascade. Caffeic acid also substantially inhibited the UVB-irradiation-induced activation of MAPK signal transduction pathways and the downstream transcription factors AP-1 and nuclear factor-κB. Caffeic acid may have therapeutic potential as a topical protective agent against the deleterious effects of UVB radiation.32 Caffeic acid inhibited the TPA-dependent stimulation of DNA synthesis and increased the number of tumors.28 Caffeic acid effectively suppressed UVB-irradiation-induced COX-2 expression and prostaglandin E2 in JB6 cells and suppressed UVB-irradiation-induced skin carcinogenesis by inhibiting Fyn kinase activity.34
58.8 CONCLUSION The extract of coffee beans and leaves and its constituents—caffeine, chlorogenic acid, and caffeic acid—exhibit antioxidant and anti-inflammatory properties. These constituents diminish UVB-irradiationinduced photoaging by inhibiting MMPs and increasing type I procollagen production through ROS scavenging and downregulation of the MAPK pathway. Coffeerelated products are a promising potential agent for preventing cutaneous photodamage. Based on laboratory and epidemiological evidence, we suggest that routinely consuming coffee or topically applying coffee-related products provide effective protection against the harmful effects of UV irradiation from sunlight, including photoaging and photocarcinogenesis.
58.9 SUMMARY POINTS • C onsuming coffee reduces the risk of skin cancer. • Coffee extract and its constituents exhibit antioxidant and anti-inflammatory properties. • Coffee extract diminishes UVB-irradiation-induced photoaging by modulating the MAPK/MMP/type I procollagen pathway. • Topically applying and orally administering caffeine may prevent UV-irradiation-induced photoaging and photocarcinogenesis. • Coffee-related products are a promising potential agent for preventing cutaneous photodamage.
References 1. Andersen LF, Jacobs Jr DR, Carlsen MH, Blomhoff R. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. Am J Clin Nutr 2006;83(5):1039–46. 2. George SE, Ramalakshmi K, Mohan Rao LJ. A perception on health benefits of coffee. Crit Rev Food Sci Nutr 2008;48(5):464–86. 3. Clifford MN, Wu W, Kirkpatrick J, Kuhnert N. Profiling the chlorogenic acids and other caffeic acid derivatives of herbal chrysanthemum by LC-MSn. J Agric Food Chem 2007;55(3):929–36. 4. Baumann L, Woolery-Lloyd H, Friedman A. “Natural” ingredients in cosmetic dermatology. J Drugs Dermatol 2009;8(6 Suppl.):s5–9. 5. Chiang HM, Chen HC, Lin TJ, Shih IC, Wen KC. Michelia alba extract attenuates UVB-induced expression of matrix metalloproteinases via MAP kinase pathway in human dermal fibroblasts. Food Chem Toxicol 2012;50(12):4260–9. 6. Rittie L, Fisher GJ. UV-light-induced signal cascades and skin aging. Ageing Res Rev 2002;1(4):705–20. 7. Yaar M, Gilchrest BA. Photoageing: mechanism, prevention and therapy. Br J Dermatol 2007;157(5):874–87. 8. Wen KC, Fan PC, Tsai SY, Shih IC, Chiang HM. Ixora parviflora protects against UVB-induced photoaging by inhibiting the expression of MMPs, MAP kinases, and COX-2 and by promoting type I procollagen synthesis. Evid Based Complement Alternat Med 2012;2012:417346. 9. Chiang HM, Lin TJ, Chiu CY, et al. Coffea arabica extract and its constituents prevent photoaging by suppressing MMPs expression and MAP kinase pathway. Food Chem Toxicol 2011;49(1):309–18.
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10. O’Kane S, Ferguson MW. Transforming growth factor beta s and wound healing. Int J Biochem Cell Biol 1997;29(1):63–78. 11. Schrader A, Siefken W, Kueper T, et al. Effects of glyceryl glucoside on AQP3 expression, barrier function and hydration of human skin. Skin Pharmacol Physiol 2012;25(4):192–9. 12. Lu YP, Lou YR, Peng QY, Xie JG, Nghiem P, Conney AH. Effect of caffeine on the ATR/Chk1 pathway in the epidermis of UVBirradiated mice. Cancer Res 2008;68(7):2523–9. 13. Farris P. Idebenone, green tea, and Coffeeberry extract: new and innovative antioxidants. Dermatol Ther 2007;20(5):322–9. 14. Velazquez Pereda Mdel C, Dieamant Gde C, Eberlin S, et al. Effect of green Coffea arabica L. seed oil on extracellular matrix components and water-channel expression in in vitro and ex vivo human skin models. J Cosmet Dermatol 2009;8(1):56–62. 15. Silverberg JI, Patel M, Brody N, Jagdeo J. Caffeine protects human skin fibroblasts from acute reactive oxygen species-induced necrosis. J Drugs Dermatol 2012;11(11):1342–6. 16. Husein-ElAhmed H, Aneiros-Fernandez J, Gutierrez-Salmeron MT, Aneiros-Cachaza J, Naranjo-Sintes R. Relationship between food intake and cutaneous solar elastosis adjacent to basal cell carcinoma. J Eur Acad Dermatol Venereol 2013;27(1):25–30. 17. Ekiz O, Yuce G, Ulasli SS, Ekiz F, Yuce S, Basar O. Factors influencing skin ageing in a Mediterranean population from Turkey. Clin Exp Dermatol 2012;37(5):492–6. 18. Boden I, Nystrom J, Geladi P, Naredi P, Lindholm-Sethson B. NIR and skin impedance spectroscopic measurements for studying the effect of coffee and alcohol on skin, and dysplastic naevi. Skin Res Technol 2012;18(4):486–94. 19. Abel EL, Hendrix SO, McNeeley SG, et al. Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women. Eur J Cancer Prev 2007;16(5):446–52. 20. Naldi L, Gallus S, Tavani A, Imberti GL, La Vecchia C. Risk of melanoma and vitamin A, coffee and alcohol: a case-control study from Italy. Eur J Cancer Prev 2004;13(6):503–8. 21. Milan T, Verkasalo PK, Kaprio J, Koskenvuo M. Lifestyle differences in twin pairs discordant for basal cell carcinoma of the skin. Br J Dermatol 2003;149(1):115–23. 22. Veierod MB, Thelle DS, Laake P. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Int J Cancer 1997;71(4):600–4. 23. Conney AH, Kramata P, Lou YR, Lu YP. Effect of caffeine on UVBinduced carcinogenesis, apoptosis, and the elimination of UVBinduced patches of p53 mutant epidermal cells in SKH-1 mice. Photochem Photobiol 2008;84(2):330–8. 24. Herman A, Herman AP. Caffeine’s mechanisms of action and its cosmetic use. Skin Pharmacol Physiol 2013;26(1):8–14. 25. Conney AH, Lou YR, Nghiem P, Bernard JJ, Wagner GC, Lu YP. Inhibition of UVB-induced nonmelanoma skin cancer: a path from tea to caffeine to exercise to decreased tissue fat. Top Curr Chem 2013;329:61–72. 26. Kerzendorfer C, O’Driscoll M. UVB and caffeine: inhibiting the DNA damage response to protect against the adverse effects of UVB. J Invest Dermatol 2009;129(7):1611–3. 27. Heffernan TP, Kawasumi M, Blasina A, Anderes K, Conney AH, Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J Invest Dermatol 2009;129(7):1805–15. 28. Kawasumi M, Lemos B, Bradner JE, et al. Protection from UV- induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Natl Acad Sci USA 2011;108(33):13716–21. 29. Lu YP, Lou YR, Peng QY, Nghiem P, Conney AH. Caffeine decreases phospho-Chk1 (Ser317) and increases mitotic cells with cyclin B1 and caspase 3 in tumors from UVB-treated mice. Cancer Prev Res (Phila) 2011;4(7):1118–25.
30. Koo SW, Hirakawa S, Fujii S, Kawasumi M, Nghiem P. Protection from photodamage by topical application of caffeine after ultraviolet irradiation. Br J Dermatol 2007;156(5):957–64. 31. Lu YP, Lou YR, Liao J, et al. Administration of green tea or caffeine enhances the disappearance of UVB-induced patches of mutant p53 positive epidermal cells in SKH-1 mice. Carcinogenesis 2005;26(8):1465–72. 32. Lu YP, Lou YR, Peng QY, Xie JG, Conney AH. Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in the epidermis of p53 and Bax knockout mice. Cancer Res 2004;64(14):5020–7. 33. Lu YP, Lou YR, Xie JG, et al. Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis 2007;28(1):199–206. 34. Han W, Ming M, He YY. Caffeine promotes ultraviolet B-induced apoptosis in human keratinocytes without complete DNA repair. J Biol Chem 2011;286(26):22825–32. 35. He Z, Ma WY, Hashimoto T, Bode AM, Yang CS, Dong Z. Induction of apoptosis by caffeine is mediated by the p53, Bax, and caspase 3 pathways. Cancer Res 2003;63(15):4396–401. 36. Hashimoto T, He Z, Ma WY, et al. Caffeine inhibits cell proliferation by G0/G1 phase arrest in JB6 cells. Cancer Res 2004;64(9):3344–9. 37. Feng R, Lu Y, Bowman LL, Qian Y, Castranova V, Ding M. Inhibition of activator protein-1, NF-kappaB, and MAPKs and induction of phase 2 detoxifying enzyme activity by chlorogenic acid. J Biol Chem 2005;280(30):27888–95. 38. Kitagawa S, Yoshii K, Morita SY, Teraoka R. Efficient topical delivery of chlorogenic acid by an oil-in-water microemulsion to protect skin against UV-induced damage. Chem Pharm Bull 2011;59(6):793–6. 39. Huang MT, Xie JG, Wang ZY, et al. Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea. Cancer Res 1997;57(13):2623–9. 40. Chen WC, Liou SS, Tzeng TF, Lee SL, Liu IM. Effect of topical application of chlorogenic acid on excision wound healing in Rats. Planta Medica 2013;79(8):616–21. 41. Pluemsamran T, Onkoksoong T, Panich U. Caffeic acid and ferulic acid inhibit UVA-induced matrix metalloproteinase-1 through regulation of antioxidant defense system in keratinocyte HaCaT cells. Photochem Photobiol 2012;88(4):961–8. 42. Saija A, Tomaino A, Trombetta D, et al. In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents. Int J Pharm 2000;199(1):39–47. 43. Staniforth V, Chiu LT, Yang NS. Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse. Carcinogenesis 2006;27(9):1803–11. 44. Kang NJ, Lee KW, Shin BJ, et al. Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVBinduced COX-2 expression. Carcinogenesis 2009;30(2):321–30. 45. Song F, Qureshi AA, Han J. Increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin. Cancer Res 2012;72(13):3282–9. 46. Szeto YT, Tong HH. Caffeine as a photoprotective agent for diminishing phototoxicity. Toxicol Ind Health 2010;26(10):667–70. 47. Jagdeo J, Brody N. Complementary antioxidant function of caffeine and green tea polyphenols in normal human skin fibroblasts. J Drugs Dermatol 2011;10(7):753–61. 48. Lou YR, Lu YP, Xie JG, Huang MT, Conney AH. Effects of oral administration of tea, decaffeinated tea, and caffeine on the formation and growth of tumors in high-risk SKH-1 mice previously treated with ultraviolet B light. Nutr Cancer 1999;33(2):146–53. 49. Lu YP, Lou YR, Xie JG, et al. Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci United SA 2002;99(19):12455–60.
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Role of Coffea arabica Extract and Related Compounds in Preventing Photoaging and Photodamage of the Skin Hsiu-Mei Chiang, Chien-Wen Chen, Chien-Chia Chen, Hsiao-Wen Wang, Jhe-Hua Jhang, Ya-Han Huang, Kuo-Ching Wen Department of Cosmeceutics, China Medical University, Taichung, Taiwan
List of Abbreviations
photoaging and skin cancer risk,4,5 has recently drawn a considerable amount of interest. Natural products possessing anti-inflammatory, immunomodulatory, and antioxidant properties have been exploited as ideal chemopreventive agents for various skin disorders. In addition, bench works and epidemiological studies have provided evidence supporting the use of certain botanical ingredients, such as coffee berries and leaves, and the findings regarding the proposed biological mechanisms have been applied in the cosmetics industry.4
AQP-3 Aquaglycerolporins-3 ECM Extracellular matrix GAGs Glycosaminoglycans GM-CSF Granulocyte-macrophage colony-stimulating factor MAPK Mitogen-activated protein kinase MMP Matrix metalloproteinase NMFs Natural moisturizing factors ROS Reactive oxygen species TGF-β1 Transforming growth factor-β1 UV Ultraviolet
58.1 INTRODUCTION
58.2 AGING AND PHOTOAGING
Coffee is one of the most popular drinks worldwide. Coffee consumption, a major source of dietary antioxidants, inhibits inflammation and therefore reduces the risk of cardiovascular disease and other inflammatory diseases in postmenopausal women.1 Coffee extract scavenges superoxide free radicals and inhibits lipid peroxidation, hepatitis B virus expression, and enterobacteria growth. Coffee is a complex mixture of chemicals, and the components of Coffea arabica are diterpenoid alcohols (such as cafestol and kahweol), an alkaloid (caffeine), and phenolic acids (caffeic acid and chlorogenic acid)2 (Figure 58.1). Coffee contains an abundance of polyphenols and phenolic acids, including chlorogenic acids, caffeoylquinic acids, feruloylquinic acids, dicaffeoylquinic acids, p-coumaroylquinic acids, caffeic acid, ferulic acid, and their derivatives.2,3 Using natural products for preventing ultraviolet (UV)-irradiation-induced photodamage, including
Skin aging is a progressive process that can be divided into intrinsic and extrinsic aging.6 UV irradiation is the major cause of extrinsic aging; extrinsic aging caused by UV irradiation is called photoaging. Intrinsic aging is characterized by smooth, dry, pale, and finely wrinkled skin, whereas photoaged skin is characterized by rough, fine, coarse wrinkling and mottled hyperpigmentation on exposed areas such as the face, neck, and forearms. UV irradiation from sunlight is a potent factor in skin photoaging and photocarcinogenesis. UV irradiation generates mutagenic and carcinogenic chemical compounds that cause DNA damage (e.g., [6,4]pyrimidinepyrimidone photoproducts and cyclobutane pyrimidine dimers).7 The incidence of sunlight-induced skin cancer is increasing because of increased recreational sun exposure, the use of UV tanning beds, and the deterioration of the ozone layer. Epidemiological, clinical, and laboratory studies have indicated that solar UV irradiation is a complete carcinogen and that excessive exposure
Coffee in Health and Disease Prevention http://dx.doi.org/10.1016/B978-0-12-409517-5.00058-9
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58. COFFEE IN PHOTOAGING DAMAGE
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FIGURE 58.1 Structures of caffeine (A), caffeic acid (B), and chlorogenic acid (C).
can lead to the development of various skin disorders including melanoma and nonmelanoma skin cancers.7
58.3 MECHANISMS OF PHOTOAGING UV-irradiation-induced inflammation and the resulting accumulation of reactive oxygen species (ROS) has been reported to play a crucial role in chronologically aged and photoaged skin in vivo.5,8 Increased ROS production alters gene and protein structure and function, which leads to skin damage.6 UV irradiation also enhances collagenase activity and contributes to wrinkle formation through collagen degradation in the dermal extracellular matrix (ECM).6 UVB irradiation induces ROS production, which promotes downstream signal transduction in the dermis, causing skin damage and photoaging (Figure 58.2). UV irradiation induces the synthesis of matrix metalloproteinases (MMPs) in human skin in vivo. UVB is known to induce the overexpression of MMP-1, -3, and -9 in the normal human epidermis in vivo.5,8,9 MMP-1 initiates the degradation of type I and type III fibrillar collagens, MMP-3 activates proMMP-1, and MMP-9 further
degrades the collagen fragments generated by collagenases.5,6 UV irradiation induces the overexpression of MMPs, degrading proteins in the ECM, including collagen and elastin, and leading to the formation of coarse wrinkles and sagging skin. UV irradiation reduces the production of collagen, which is the major component of the dermis, and causes an imbalance between MMPs synthesis and degradation6 (Figure 58.2). The ECM functions as the skin skeleton in the dermis. The most abundant structural protein in skin connective tissue is type I collagen, which is responsible for contributing strength and resiliency.6,7 The degradation of collagen and elastin caused by intrinsic aging causes the loss of elasticity, sagging, stretch marks, and fine wrinkling observed in the skin. Type I collagen is synthesized as a soluble precursor, and type I procollagen is secreted by fibroblasts and proteolytically processed to form insoluble collagen fibers. In addition to collagen, elastin also contributes to skin plasticity. Collagens and elastin form a three-dimensional network that constitutes the architectural basis of the dermis and are involved in skin integrity, suppleness, and plasticity. UV irradiation enhances the secretion of elastase and degrades elastin, causing sagging of the skin.6 Disorganization, fragmentation, and dispersion of collagen bundles are prominent features of photodamaged human skin. Numerous studies have proposed that MMP-mediated collagen destruction is largely responsible for the connective tissue damage that occurs in photoaging.6 Mitogen-activated protein kinase (MAPK) activation is a photoaging pathway and a factor in MMP production in fibroblasts. c-Jun NH2-teeminal kinase (JNK) and p38 modulate c-Fos expression, and c-Fos, accompanied by c-Jun, synthesizes the transcription factor activator protein-1 (AP-1). Inhibiting extracellular signalregulated kinase (ERK), JNK, and p38 expression may suppress c-Fos and c-Jun expression and inhibit AP-1, MMP, and type I procollagen expression. Transforming growth factor (TGF)-β1 and granulocyte-macrophage colony-stimulating factor are involved in numerous aspects of connective tissue repair; they play a vital role in regulating cell growth, differentiation, biosynthesis, and the deposition of ECM compounds by fibroblasts. TGF-β1 is essential for dermal strength and is partially responsible for the contraction of the dermis. TGF-β1 activates the production of collagen, fibronectin, glycosaminoglycans, and elastin by fibroblasts and is the most powerful known stimulator of collagen synthesis.10 Hydration of the stratum corneum determines the appearance and physical properties of the skin. Skin structure, lipid and protein composition, barrier function, and natural moisturizing factors, such as free amino acids, pyrrolidone carboxylic acid, and lactate, influence skin hydration. Aquaglycerolporin-3, the water- and glycerol-transporting proteins in keratinocytes, reduce stratum corneum hydration and skin elasticity.11 These
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58.5 Coffee Prevents Skin Photoaging
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FIGURE 58.2 Mechanism of ultraviolet (UV)-irradiationinduced photoaging. AP-1, activating protein-1; ECM, extracellular matrix; MMPs, matrix metalloproteinase; ROS, reactive oxygen species.
proteins play vital roles in skin hydration and barrier function, thus preventing water loss. UV-irradiation-induced DNA damage also induces multiple signal transduction networks that coordinate cell cycle checkpoint arrest and induced apoptosis. Another vital pathway activated in response to UV irradiation is the phosphoinositol-3-kinase-like ataxia telangiectasia and Rad3-related protein kinase (ATR). UV irradiation reduces the level of cyclin B1 and messenger RNA (mRNA), preventing entry into mitosis by both an ataxia-telangiectasia mutated (ATM)– and ATR-dependent mechanism and an ATM- and ATR-independent mechanism.12 The UVBactivated ATR pathway causes phospho-checkpoint kinase 1 (Chk1)-(Ser345) to increase in keratinocytes and a marked decrease cyclin B1 in mitotic keratinocytes.12
58.4 ANTIOXIDANT ACTIVITY OF COFFEE Oxidative damage by ROS plays a major role in aging, photoaging, and carcinogenesis.7 Previous studies have reported that the phenolic content of plants contributes to antioxidant activity. Coffee and coffee berry extracts are rich in polyphenols, which are known to have a strong antioxidant effect.4 UVB irradiation induces ROS production and promotes downstream signal transduction in the dermis, causing skin damage and photoaging. Thus, inhibiting ROS production prevents the skin from photoaging. Coffee berry extract exhibits antioxidant activity mediated by potent antioxidant polyphenols, especially chlorogenic acid, proanthocyanidins, quinic acid, and ferulic acid.13 The extract of C. arabica leaves has shown significant 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and protection for 2,2’-Azobis(2-amidinopropane)
dihydrochloride (AAPH)-induced erythrocyte hemolysis.9 The extract of C. arabica leaves also inhibits UVBirradiation-induced intracellular ROS generation in human skin fibroblasts and against UVB-irradiationinhibited catalase activity, but not glutathione, in human skin fibroblasts (unpublished data). Green coffee oil also has demonstrated antioxidant ability; therefore, it prevents the deleterious actions of free radicals1 and increases ECM synthesis by scavenging free radicals.14 Low (0.01 mM) and intermediate (0.1 mM) doses of caffeine, the major constituent of coffee, protect human skin fibroblasts from hydrogen peroxide-induced cell damage.15 These studies have indicated that coffee is a potential candidate for preventing aging and photoaging.
58.5 COFFEE PREVENTS SKIN PHOTOAGING In a clinical study, patients exhibiting actinic damage of the skin used a skin care system containing Coffeeberry® extract.13 Compared with a placebo, the test cream was superior in improving fine lines, wrinkles, pigmentation, and overall appearance.13 Orally administering and topically applying antioxidant plant extracts, such as coffee extract, can protect skin from UV-irradiationinduced erythema, early aging, and irradiation-induced cancer. Studies have reported that coffee consumption is not associated with the grade of elastosis,16 facial wrinkle formation,17 and skin characteristics.18 Treating human cultured fibroblasts with Coffeeberry® showed that gene expression of several collagens and a connective tissue growth factor was upregulated and that gene expression of MMPs was downregulated.13 Coffea arabica extract-stimulated type I procollagen expression, inhibited MMP-1, -3, and -9 expression
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58. COFFEE IN PHOTOAGING DAMAGE
and inhibited the phosphorylation of JNK, ERK, and p38.9 These results show that C. arabica extract can repair photodamage in skin and increase skin barrier function through inhibiting MMP expression and the MAPK pathway (JNK, ERK, and p38).9 C. arabica extract inhibits MAPK phosphorylation and modulates c-Fos expression. Finally, a report indicated that topical products that include C. arabica or coffee berry extract are considered safe.13 Green coffee oil stimulated the synthesis of proteins in the ECM, including collagen, elastin, and glycosaminoglycans. In addition, it increased the release of TGF-β1 and granulocyte-macrophage colony-stimulating factor in normal human dermal fibroblasts.14 It also induced the expression of aquaglycerolporin-3 mRNA in normal human dermal fibroblasts to prevent water loss in the dermis, and it might improve physiological balance in the skin.14
58.6 COFFEE PREVENTS SKIN TUMOR FORMATION In epidemiological studies, daily intake of caffeinecontaining coffee reduces the incidence of skin cancers such as nonmelanoma skin cancer. Daily caffeinated coffee consumption was associated with a dose-related, reduced prevalence of nonmelanoma skin cancer in Caucasian women. Women who drink caffeinated coffee on a daily basis had a 10.8% lower prevalence of nonmelanoma skin cancer, and six or more cups per day was associated with a 36% reduction in nonmelanoma skin cancer. However, in contrast to caffeinated coffee, daily consumption of decaffeinated coffee was not associated with a substantial change in self-reported nonmelanoma skin cancer. Each additional cup of caffeinated coffee ingested was associated with a 5% decrease in the risk of developing nonmelanoma skin cancer, whereas drinking decaffeinated coffee showed no such association.19 In another study, coffee consumption was not associated with cutaneous malignant melanoma risk20 and basal cell carcinoma.21 However, one study indicated that drinking coffee substantially reduces cutaneous malignant melanoma risk in women but not in men.22 Coffee consumption studies related to human skin disorders are summarized in Table 58.1. According to animal studies, orally administering a caffeine solution inhibits UVB-irradiation-induced complete carcinogenesis in SKH-1 mice. Orally administering coffee or a caffeine solution for 2 weeks enhanced UVB-irradiation-induced increases in apoptosis in the epidermis, but these treatments had no effect in the non-UVB-treated normal epidermis. Administering coffee and caffeine may inhibit UVB-irradiation-induced carcinogenesis by enhancing UVB-induced apoptosis.23
TABLE 58.1 Epidemiologic Studies of the Effect of Coffee Consumption on Photoaging and Skin Cancer Subjects
Results
References
Norwegian men and Reduced risk of cutaneous 22 women malignant melanoma in women but not in men Caucasian women
Dose-related decreased prevalence of nonmelanoma skin cancer
19
Healthy individuals
No influence on the results of skin impedance spectroscopic measurements
18
Mediterranean population
No influence on skin aging and wrinkle formation
16,17
Basal cell carcinoma, Reduced basal cell carcinoma squamous cell risk but not risk of squamous carcinoma, and cell carcinoma and melanoma melanoma cases
45
Long-term (20-week) topical application of caffeine to mice previously treated with UVB irradiation inhibited tumor formation and stimulated apoptosis in tumor cells.
58.7 EFFECT OF COFFEE CONSTITUENTS ON PHOTOAGING AND PHOTOCARCINOGENESIS Coffee is a complex mixture of chemicals and contains substantial amounts of caffeine, chlorogenic acid, and other phenolic acids. Chlorogenic acid, caffeic acid, and caffeine, which contribute to the potential of C. arabica to effectively prevent photoaging. Studies of the role of coffee constituents in protecting skin from UV irradiation are summarized in Tables 58.2–58.4.
58.7.1 Caffeine Caffeine is a key component in numerous popular drinks, especially tea and coffee. Caffeine is increasingly used in cosmetics because of its high biological activity and ability to penetrate the skin barrier.4,38 Tissue fat secretes antiapoptotic adipokines that have a tumor-promoting effect. Caffeine stimulates the degradation of fats by inhibiting phosphodiesterase activity and is popularly used as an active compound in anticellulite products that may contribute to anticarcinogenic activity.39 Caffeine also exhibits potent antioxidant properties and inhibits lipid peroxidation. It helps protect cells from UV irradiation and slows the process of photoaging and carcinogenesis of the skin.38,39 Increasing molecular, cellular, and epidemiological evidence suggests that caffeine
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58.7 Effect of Coffee Constituents on Photoaging and Photocarcinogenesis
TABLE 58.2 The Activities of Caffeine in Skin Cells and Animal Studies Materials
Model
Results
References
Caffeine
Primary human keratinocytes
Inhibited ATR-Chk1
24
Human keratinocytes (HaCaT)
Blocked UVB-induced Chk1 and AKT phosphorylation Upregulated COX-2 Promoted apoptosis
25
Human lymphocytes
Reduced 5-methoxypsolaren-induced phototoxicity
46
Human skin fibroblasts
Antioxidant Inhibited H2O2-generated free radicals and 4-hydroxy-2-nonenal
47
JB6 Cl41 cells
Induced phosphorylation of p53 Elevated bax expression Increased cleavaged caspase-3
26
JB6 Cl41 cells
Suppressed cell cycle progression at the G0/G1 phase Inhibited phosphorylation of retinoblastoma protein at Ser780 and Ser807/Ser811 inhibited the activation of the cyclin D1-cdk4 complex
27
SKH-1 hairless mice
Inhibited tumor formation and growth
48
SKH-1 hairless mice
Decreased UVB-induced keratoacanthomas and squamous cell carcinomas
28
SKH-1 hairless mice
Decreased UVB-induced phospho-Chk1 (Ser317) Increased mitotic cells with cyclin B1 and caspase-3 Enhanced UVB-induced apoptosis in epidermis
29
SKH-1 hairless mice
Promoted the deletion of DNA-damaged keratinocytes
30
SKH-1 hairless mice
Decrease UVB-induced nonmalignant and malignant skin tumors
49
SKH-1 hairless mice
Decreased UVB-induced thymine dimers Inhibited UVB-induced sunburn skin lesions
31
Oral caffeine
Topical caffeine
Dermabase cream containing caffeine
Chk1, checkpoint kinase 1; COX-2, cyclooxygenase 2; H2O2, hydrogen peroxide; UV, ultraviolet.
TABLE 58.3 Activities of Caffeic Acid in Skin Cells and Animal Studies Material
Model
Results
Reference
Caffeic acid
BALB/cBYJ mice
Inhibited UVB-induced interleukin-10 expression and mitogen-activated protein kinase
32
Caffeic acid
Human keratinocytes (HaCaT)
Inhibited UVA-induced cytotoxicity Induced MMP-1 activity and mRNA Upregulated antioxidant system
33
Caffeic acid
Mouse skin epidermal (JB6) cells
Suppressed UVB-induced COX-2 expression and prostaglandin E2 Suppressed UVB-induced skin carcinogenesis by inhibiting Fyn kinase activity
34
Caffeic acid (topical)
Human skin
Reduced UVB-induced erythema
35
COX-2, cyclooxygenase 2; MMP, matrix metalloproteinase; mRNA, messenger RNA; UV, ultraviolet.
may have a substantial protective effect against UV-irradiation-induced carcinogenesis in mice and humans.19 Caffeine selectively induces apoptosis in UV-damaged keratinocytes but not in undamaged areas.23 Caffeine inhibits ATR and ATM kinases, both of which are central components of the DNA damage response.40 Following UVB irradiation, caffeine also induces an apoptotic response through caspase-3 and
poly(ADP-ribose) polymerase cleavage,24,29,41 reduces phospho-Chk1 (Ser317), and increases cyclin B1 in mitotic cells.29 Topically applying caffeine inhibits carcinogenesis and promotes apoptosis in the sunburned cells of UVB-pretreated hairless SKH-1 mice. Moreover, UV-irradiation-induced skin roughness and transverse rhytids in mice decreased when caffeine was topically applied after exposure to UV light.30
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58. COFFEE IN PHOTOAGING DAMAGE
TABLE 58.4 Activities of Chlorogenic Acid in Skin Cells and Animal Studies Material
Model
Results
Reference
Chlorogenic acid
Human skin fibroblasts
Inhibited MMP-3 9 Did not restore UVB-induced type 1 procollagen damage
Rats
Antioxidant Increased cell proliferation
36
Guinea pig skin
Prevented UVinduced erythema
37
MMP, matrix metalloproteinase; UV, ultraviolet.
Orally administering caffeine to mice markedly inhibited UVB-irradiation-induced Chk1 phosphorylation on serine 345 in the epidermis, indicating that the ATRChk1 pathway can be inhibited in the target tissue by administering caffeine.40 Topically applying caffeine to mice enhanced p53-mutated cells eliminated from skin keratinocytes, indicating that caffeine may prevent UVirradiation-induced skin cancer development. In addition, p53 is not required to produce the effect of caffeine because p53-mutant patches of keratinocytes were selectively killed when caffeine was topically applied.42 A potential mechanism of the inhibitory effect of caffeine is induced apoptosis in keratinocytes damaged by UV irradiation. Even long after UV exposure was complete, the topical application of caffeine selectively induced apoptosis in nonmalignant tumors and squamous cell carcinomas without affecting neighboring “normal” nontumorous skin in mice.23 SKH-1 hairless mice were irradiated with UVB twice weekly for 20 weeks. These tumor-free mice then were treated topically with caffeine once each day, 5 days/ week, for 18 weeks but were not treated with UVB. Topical applications of caffeine to these mice reduced the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively.23 In addition to the stimulatory effect of caffeine on UVB-irradiationinduced apoptosis in the epidermis23,43 and apoptosis in tumors,23 caffeine also exhibited a sunscreen effect.31 Caffeine has a selective apoptotic effect in UVB- irradiation-induced DNA damage in the epidermis and in tumors but does not cause apoptosis in normal epidermis or in nontumor areas adjacent to tumors.23 Caffeine promoted apoptosis in primary human keratinocytes by inhibiting the ATR-Chk1 pathway. Activation of the ATR-Chk1 pathway normally results in cell cycle checkpoint activation. Applying an ATR pathway inhibitor such as caffeine may protect the skin from UVB irradiation by augmenting the apoptotic elimination of UVBdamaged keratinocytes independent of the status of p53. Mechanistic studies indicate that caffeine administration
enhances UVB-irradiation-induced apoptosis in the mouse epidermis by increasing wild-type p5323 and through a p53- and bax-independent mechanism.43 Studies of a p53-independent mechanism suggest that caffeine may enhance UVB-irradiation-induced apoptosis by inhibiting the ATR-mediated phosphorylation of Chk1, increasing the level of cyclin B1 and abrogating the UVB-irradiation-induced blockage at the G2 checkpoint, thereby resulting in lethal mitosis.23 Caffeine effectively inhibits the UVB-induced AKT/cyclooxygenase-2 (COX-2) pathway independent of the ATR kinase and blocks AKT/COX-2 signaling by specifically eliminating UVB-irradiation-damaged keratinocytes without complete DNA repair through apoptosis.25 In another study, low concentrations of caffeine induced apoptosis in JB6 Cl41 cells. The cells showed the typical DNA laddering pattern and other characteristics of apoptosis.26 The IC50 of caffeine on JB6 Cl41 cells was 2.7 mM. The apoptosis that was induced by caffeine seemed to be p53-dependent because cells lacking p53 (p53(−/−)) showed no signs of apoptosis after treatment with caffeine. Caffeine induced the phosphorylation of p53 at Ser-15 in JB6 Cl41 cells, increased p53 activation and the expression of Bax, and cleaved caspase-3.26 The results indicated that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase-3 pathways.26 Caffeine inhibited cell growth and signal-induced activation of cdk4, thereby suppressing the progression of quiescent cells in the cell cycle in the mouse epidermal cell line (JB6 cell).27 Caffeine may prevent the DNA-damaging effect of UVB on skin.
58.7.2 Chlorogenic Acid Chlorogenic acid inhibits MMP-3 expression, but not expression of MMP-1 and MMP-9, and does not restore UVB-irradiation-induced type I procollagen damage.9 However, chlorogenic acid has been reported to inhibit the MMP-9 activity of the hepatocellular carcinoma cell line (Hep3B). Pretreating JB6 cells with chlorogenic acid blocked UVB-irradiation- or 12-o-tetradecanoylphorbol13-acetate (TPA)-induced transactivation of AP-1 and nuclear factor-κB, and chlorogenic acid reduced the phosphorylation of JNK, p38 kinase, and ERK induced by UVB or TPA.44 Pretreating guinea pig dorsal skin with chlorogenic acid containing microemulsion gel prevented erythema formation induced by UV irradiation.37 Chlorogenic acid also was reported to inhibit the TPA-dependent stimulation of DNA synthesis and reduce the number of tumors.28 Chlorogenic acid exhibited potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione and reducing lipid peroxidation in rats. Chlorogenic acid improved cellular proliferation and increased epithelialization rates. It also increased
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References
tumor necrosis factor-α levels during the inflammatory phase of wound healing, upregulated TGF-β1, and enhanced collagen IV synthesis. Topically applying chlorogenic acid accelerates the process of excision wound healing.36
58.7.3 Caffeic Acid Caffeic acid, a phenolic acid present in numerous dietary plants, was shown to exhibit antioxidant, antiinflammatory, and anticancer activities. Caffeic acid inhibited UVB-irradiation-induced overexpression of MMP-1 and -9, but not of MMP-3, in human skin fibroblasts.9 In addition, caffeic acid did not prevent UVBirradiation-induced type I procollagen degradation.9 In a previous study, caffeic acid applied on abdominal skin suppressed UVA-irradiation-induced ROS; caffeic acid existed in the skin after oral ingestion. Caffeic acid pretreatment reduced the cytotoxicity of the HaCaT after UVA irradiation33 and suppressed UVA- irradiationinduced MMP-1 activity and mRNA oxidant formation. Caffeic acid also upregulated glutathione content, mRNA of γ-glutamate cysteine ligase and its activities, and mRNA expression of catalase and glutathione peroxidase in UVA-irradiated cells. Therefore, caffeic acid produced protective effects on UVA-irradiation-mediated MMP-1 induction in HaCaT cells, possibly because it restores the antioxidant defense system at the cellular and molecular levels.33 In addition, caffeic acid showed weak collagenolytic activity. Topically applying caffeic acid protected the skin from UVB-irradiation-induced erythema.35 In vitro and in vivo experiments demonstrated that caffeic acid may be successfully used as a topical protective agent against UV-irradiation-induced skin damage.35 Caffeic acid attenuates the local immune suppression induced by UVB irradiation and inhibits the transcriptional activation of the UVB-irradiation-induced interleukin (IL)-10 promoter, IL-10 mRNA expression, and protein production in mouse skin.32 Caffeic acid might inhibit IL-10 production by interfering with prostaglandin E2 synthesis, which is involved in activating the UVB-irradiation-induced immune suppressive cytokine cascade. Caffeic acid also substantially inhibited the UVB-irradiation-induced activation of MAPK signal transduction pathways and the downstream transcription factors AP-1 and nuclear factor-κB. Caffeic acid may have therapeutic potential as a topical protective agent against the deleterious effects of UVB radiation.32 Caffeic acid inhibited the TPA-dependent stimulation of DNA synthesis and increased the number of tumors.28 Caffeic acid effectively suppressed UVB-irradiation-induced COX-2 expression and prostaglandin E2 in JB6 cells and suppressed UVB-irradiation-induced skin carcinogenesis by inhibiting Fyn kinase activity.34
58.8 CONCLUSION The extract of coffee beans and leaves and its constituents—caffeine, chlorogenic acid, and caffeic acid—exhibit antioxidant and anti-inflammatory properties. These constituents diminish UVB-irradiationinduced photoaging by inhibiting MMPs and increasing type I procollagen production through ROS scavenging and downregulation of the MAPK pathway. Coffeerelated products are a promising potential agent for preventing cutaneous photodamage. Based on laboratory and epidemiological evidence, we suggest that routinely consuming coffee or topically applying coffee-related products provide effective protection against the harmful effects of UV irradiation from sunlight, including photoaging and photocarcinogenesis.
58.9 SUMMARY POINTS • C onsuming coffee reduces the risk of skin cancer. • Coffee extract and its constituents exhibit antioxidant and anti-inflammatory properties. • Coffee extract diminishes UVB-irradiation-induced photoaging by modulating the MAPK/MMP/type I procollagen pathway. • Topically applying and orally administering caffeine may prevent UV-irradiation-induced photoaging and photocarcinogenesis. • Coffee-related products are a promising potential agent for preventing cutaneous photodamage.
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