Counteraction of skin inflammation and aging or cancer by polyphenols and flavonoids from polypodium leucotomos and xanthohumol

Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry

Volumn 9, Issue 2, 2010, Pages 142-149

  Philips, Neena ^a   Bynum, David ^a   Hwang, Hyeondo ^a  

^a FAIRLEIGH DICKINSON UNIVERSITY   (United States)

Author keywords

Extracellular matrix; Inflammation; Polypodium leucotomos; Transforming growth factor ; Ultraviolet radiation; Xanthohumol

Indexed keywords

8 PRENYLNARINGENIN; ALPHA CYANO 4 HYDROXYCINNAMIC ACID; CAFFEIC ACID; CHLOROGENIC ACID; COLLAGEN; CYTOKINE; DNA; ELASTIN; FERULIC ACID; FIBRILLIN; FLAVONOID; GELATINASE A; GELATINASE B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 6; INTERSTITIAL COLLAGENASE; ISOXANTHOHUMOL; NITRIC OXIDE; POLYPHENOL; POLYPODIUM LEUCOTOMOS EXTRACT; PROSTAGLANDIN; PROSTAGLANDIN SYNTHASE; REACTIVE OXYGEN METABOLITE; STROMELYSIN; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VANILLIC ACID; XANTHOHUMOL;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; BASEMENT MEMBRANE; CELL DAMAGE; CUTANEOUS PARAMETERS; DNA DAMAGE; DRUG STRUCTURE; ENZYME DEGRADATION; EXTRACELLULAR MATRIX; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; KERATINOCYTE; NEUTROPHIL; NONHUMAN; OXIDATIVE STRESS; PHOTOAGING; POLYPODIUM; POLYPODIUM LEUCOTOMOS; PROTEIN SYNTHESIS; RADIATION CARCINOGENESIS; SKIN CANCER; SKIN CARCINOGENESIS; SKIN FIBROBLAST; SKIN INFLAMMATION;

EID: 80054850633     PISSN: 18715230     EISSN: 1875614X     Source Type: Journal    
DOI: 10.2174/187152310791110625     Document Type: Article

References (99)

1. Astner, S.; Wu, A.; Chen, J.; Philips, N.; Rius-Diaz, F.; Parrado, C.; Mihm, M.C.; Goukassian, D.A.; Pathak, M.A.; González, S. Dietary lutein/zeaxanthin reduces photoaging and photocarcino-genesis in chronically UVB irradiated SKH -1 hairless mice. Skin Pharmacol. Physiol., 2007, 20, 283-281.
2. Bennett, D.C. Ultraviolet wavebands and melanoma initiation. Melannoma Res., 2008, 21, 520-524.
3. Berton, A.; Godeau, G.; Emonard, H.; Baba, K.; Bellon, P.; Horne-Beck, W.; Bellon, G. Analysis of the ex vivo specificity of human gelatinases A and B towards skin collagen and elastic fibers by computerized morphometry. Matrix Biol., 2000, 19, 139-148.
4. Gebhardt, C.; Averbeck, M.; Veirtel, A.; Kauer, F.; Saalbach, A.; Anderegg, U.; Simon, J.C. Ultraviolet-B irradiation enhances melanoma cell motility via induction of autocrine interleukin 8 secretion. Exp. Dermatol, 2007, 16, 636-643.
5. Molho-Pessach, V.; Lotem, M. Ultraviolet radiation and cutaneous carcinogenesis. Curr. Probl. Dermatol, 2007, 35, 14-27.
6. Ullrich, S.E. Sunlight and skin cancer: lessons from the immune system. Mol Carcinog., 2007, 46, 629-633.
7. González, S.; Pathak, M.A. Inhibition of ultraviolet-induced formation of reactive oxygen species, lipid peroxidation, erythema and skin photosensitization by polypodium leucotomos. Photodermatol. Photoimmunol Photomed., 1996, 12, 45-56.
8. Gonzalez, S.; Pathak, M.A.; Cuevas, J.; Villarrubia, V.G.; Fitz-Patrick, T.B. Topical or oral administration with an extract of polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of langerhans cells in human skin. Photodermatol. Photoimmunol. Photomed., 1997, 13, 50-60.
9. Middelkamp-Hup, M.A.; Pathak, M.A.; Parrado, C; Goukassian, D.; Rius-Díaz, F.; Mihm, M.C.; Fitzpatrick, T.B.; González, S. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. J. Am. Acad. Dermatol, 2004, 51, 910-918.
10. Ricciarelli, R.; Maroni, P.; Ozer, N.; Zingg, J.M.; Azzi, A. Age-dependent increase of collagenase expression can be reduced by al-pha-tocopherol via protein kinase C inhibition. Free Radic. Biol. Med., 1999, 27, 729-737.
11. Rijken, F.; Kiekens, R.C.; Bruijnzeek, P.L. Skin-infiltrating neutrophils following exposure to solar-simulated radiation could play an important role in photoageing of human skin. Br. J. Dermatol, 2005, 152, 321-328.
12. Rijken, F.; Kiekens, R.C.; Van Den Worm, E.; Lee, P.L.; Van Weelden, H.; Bruijnzeek, P.L. Pathophysiology of photoaging of human skin: focus on neutrophils. Photochem. Photobiol Sci., 2006,5, 184-189.
13. Taihao, Q.; Tianyuan, He.; Sewon, K.; Voorhees, J.J.; Fisher, G.J. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-p type II recep-tor/Smad signaling. Am. J. Pathol, 2004, 165, 741-751.
14. th ed., 2007,
15. Wilgus, T.A.; Matthies, A.M.; Radek, K.A.; Dovi, J.V.; Burns, A.L.; Shankar, R.; DiPetro, L.A. Novel function for vascular endothelial growth factor receptor-1 on epidermal keratinocytes. Am. J. Pathol, 2005, 167, 1257-1266.
16. Trompezinski, S.; Pernet, I.; Schmitt, D.; Viac, J. UV radiation and prostaglandin E2 up- regulate vascular endothelial growth factor (VEGF) in cultured human fibroblasts. Inflamm. Res., 2001, 50, 422-427.
17. Zittermann, S.I.; Issekutz, A.C. Endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation. J. Leukocyte Biol., 2006, 80, 247-257.
18. Roomi, M.W.; Roomi, N.; Ivanov, V.; Kalinovsky, T.; Niedz-wiecki, A.; Rath, M. Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis. Oncol. Reports, 2005, 14, 807-815.
19. Elias, P.M.; Arbiser, J.; Brown, B.E.; Rossiter, H.; Man, M.; Cerimele, F.; Crumrine, D.; Gunathilake, R.; Choi, E.H.; Uchida, Y.; Tschachler, E.; Feingold, K.R. Epidermal vascular endothelial growth factor production is required for permeability barrier ho-meostasis, dermal angiogenesis, and the development of epidermal hyperplasia. A. J. Pathol, 2008, 173, 689-699.
20. Munaut, C; Noel, A.; Hougrand, O.; Foidart, J.M.; Boniver, J.; Deprez, M. Vascular endothelial growth factor expression correlates with matrix methalloproteinases MT1- MMP, MMP-2 and MMP-9 in human glioblastomas. Int. J. Cancer., 2003, 106, 848-855.
21. Tas, F.; Duranyildiz, D.; Oguz, H.; Camlica, H.; Yasasever, V.; Topuz, E. Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP- 3), and BCL-2 in malignant melanoma. Med. Oncol, 2008, 25, 431-436.
22. Kosmadaki, M.G.; Yaar, M.; Arble, B.L.; Gilchrest, B.A. UV induces VEGF through a TNF-alpha independent pathway. FASEB J., 2003, 17, 446-448.
23. Trompezinski, S.; Denis, A.; Schmitt, D.; Viac, J. IL-10 is unable to downregulate VEGF expression in human activated keratino-cytes. Arch. Dermatol. Res., 2002, 294, 377-379.
24. Soriani, M.; Luscher, P.; Tyrrell, R.M. Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells. Carcinogenesis, 1999, 20, 727-732.
25. Abeyama, K.; Eng, W.; Jester, J.V.; Vink, A.A.; Edelbaum, D.; Cockerell, C.J.; Bergstresser, P.R.; Takashima, A. A role for NF-transactivation in sunburn. J. Clin. Invest, 2000, 105, 1751-1759.
26. Katiyar, S.K. UV-induced immune suppression and photocarcino-genesis: Chemoprevention by dietary botanical agents. Cancer Lett, 2007, 255, 1-11.
27. Schmitt, D.A.; Walterscheid, J.P.; Ullrich, S.E. Reversal of ultraviolet radiation-induced immune suppression by recombinant inter-leukin-12: Suppression of cytokine production. Immunology, 2000, 101, 90-96.
28. Reitamo, S.; Remitz, A.; Tamai, K.; Ledo, I.; Uitto, J. Interleukin 10 up-regulates elastin gene expression in vivo and in vitro at the transcriptional level. Biochem. J., 1994, 302, 331-333.
29. Meeran, S.M.; Katiyar, S.; Elmets, C.A.; Katiyar, S.K. Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced skin tumors. Cancer Res., 2007, 67, 8.
30. Philips, N.; Arena, R.; Yarlagadda, S. Inhibition of ultraviolet radiation mediated extracellular matrix remodeling in fibroblasts by transforming growth Factor- β. Bios, 2009, 80, 1-5.
31. Philips, N.; Conte, J.; Chen, Y.; Natrajan, P.; Taw, M.; Keller, T.; Givant, J.; Tuason, M.; Dulaj, L.; Leonardi, D.; Gonzalez, S. Beneficial regulation of matrix metalloproteinases and its inhibitors, fibrillar collagens and transforming growth factor-P by p. leucoto-mos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells. Arch. Dermatol. Res., 2009, 301, 487-495.
32. Philips, N.; Arena, R.; Chen, Y.; Conte, J.; Natrajan, P.; Haas, G.; Gonzalez, S. Direct inhibition of elastase and matrixmetalloproteinases, and stimulation of biosynthesis of fibrillar collagens, elastin and fibrillins by xanthohumol. J. Cosmet. Sci., 2009, in press.
33. Lodish, H.; Berk, A.; Kaiser, C.A.; Krieger, M.; Scott, M.P.; Bret-scher, A.; Ploegh, H.; Matsudaira, P. Molecular Cell Biology, W.H. Freeman: USA, 2008.
34. Jung, E.; Lee, J.; Baek, J.; Jung, K.; Lee, J.; Huh, S.; Kim, S.; Koh, J.; Park, D. Effect of Camellia japonica oil on human type I procollagen production and skin barrier function. J. Ethnopharmacol, 2007, 112, 127-131.
35. Shin, M.H.; Rhie, G.E.; Park, C.H.; Kim, K.H.; Cho, K.H.; Eun, H.C.; Chung, J.H. Modulation of collagen metabolism by the topical application of dehydroepiandrosterone to human skin. J. Invest. Dermatol, 2005, 124, 315-323.
36. Varani, J.; Warner, R.L.; Gharaee-Kermani, M. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J. Invest. Dermatol, 2000, 114, 480-486.
37. Brennan, M.; Bhatti, H.; Nerusu, K.C.; Bhagavathula, N.; Kang, S.; Fisher, G.J.; Varani, J.; Voorhees, J.J. Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin. Photochem. Photobiol, 2003, 78, 43-48.
38. Doyle, G.A.; Pierce, R.A.; Parks, W.C. Transcriptional induction of collagenase-1 in differentiated monocyte-like (U937) cells is regulated by AP-1 and an upstream C/EBP- p site. J. Biol. Chem., 1997, 272, 11840-11849.
39. Khorramizadeh, M.R.; Tredget, E.E.; Telaskyr, C; Shen, Q.; Gha-hary, A. Aging differentially modulates the expression of collagen and collagenase in dermal fibroblasts. Mol Cell. Biochem., 1999, 194, 99-108.
40. Lee, C; Choi, H.; Kim, H.; Kim, D.; Chang, I.; Moon, H.T.; Lee, S.; Oh, W.K.; Woo, E. Biflavonoids isolated from selaginella tama-riscina regulate the expression of matrix metalloproteinase in human skin fibroblasts. Bioorg. Med. Chem., 2008, 16, 732-738.
41. Talvensaari-Mattila, A.; Paakko, P.; Hoyhtya, M.; Blance-Sequeiros, G.; Turpeenniemi- Hujanen, T. Matrix metalloprotein-ase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma. Cancer, 1998, 83, 1153-1162.
42. Westermarck, J.; Kahari, V.M. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J., 1999, 13, 781-792.
43. Philips, N.; Keller, T.; Gonzalez, S. TGF-P like regulation of matrix metalloproteinases by anti transforming growth factor-P? and anti transforming growth factor-P 1 antibodies in dermal fibroblasts: implications to wound healing. Wound Repair Regen., 2004, 12, 53-59.
44. Philips, N.; McFadden, K. Inhibition of transforming growth factor-beta and matrix metalloproteinases by estrogen, and prolactin in breast cancer cells. Cancer Lett, 2004, 206, 63-68.
45. Philips, N.; Keller, T.; Hendrix, C; Hamilton, S.; Arena, R.; Tuason, M.; Gonzalez, S. Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts. Arch. Dermatol. Res., 2007, 299, 373-379.
46. Millis, A.J.; Hoyle, M.; McCue, H.M.; Martini, H. Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp. Cell Res., 1992, 201, 373-379.
47. Uitto, J.; Fazio, M.J.; Olsen, D. Molecular mechanisms of cutaneous aging. J. Am Acad., 1989, 21, 614-622.
48. Tsuji, N.; Moriwaki, S.; Suzuki, Y.; Takema, Y.; Imokawa, G. The role of elastases secreted by fibroblasts in wrinkle formation: implication through selective inhibition of elastase activity. Photochem. Photobiol, 2001, 71, 283-290.
49. Cho, H.S.; Lee, M H.; J W, Lee.; No K, Park, S.K.; Lee, H.S.; Kang, S.; Cho, W.G.; Park, H.J.; Oh, K.W.; Hong, J.T. Anti-wrinkling effects of the mixture of vitamin C, vitamin E, pycno-genol and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation. Photodermatol Photoimmunol Photomed, 2007, 23, 155-162.
50. Labat-Robert, J.; Fourtanier, A.; Boyer-Lafargue, B.; Robert, L. Age dependent increase of elastase type protease activity in mouse skin. Effect of UV-irradiation. J. Photochem. Photobiol, 2000, 57, 113-118.
51. Lee, K.K.; Choi, J.D. The effects of areca catechu L extract on anti-aging. Int. J. Cosmet. Sci., 1999, 21, 285-295.
52. Jimenez, F.; Mitts, T.F.; Liu, K.; Wang, Y.; Hinek, A. Ellagic and tannic acids protect newly synthesized elastic fibers from premature enzymatic degradation in dermal fibroblast cultures. J. Invest. Dermatol, 2006, 126, 1272-1280.
53. Philips, N.; Keller, T.; Holmes, C. Reciprocal effects of ascorbate on cancer cell growth and the expression of matrix metalloproteinases and transforming growth factor-beta. Cancer Lett, 2007, 256, 49-55.
54. Sporn, M.B.; Roberts, A.B.; Wakefield, L.M.; Assoian, R.K. Transforming growth factor-beta: biological function and chemical structure. Science, 1986, 233, 532-534.
55. Ghahary, A.; Tredget, E.E.; Shen, Q. Insulin-like growth factor-II/mannose 6 phosphate receptors facilitate the matrix effects of latent transforming growth factor-beta 1 released from genetically modified keratinocytes in a fibroblast/keratinocyte co-culture system. J. Cell Physiol, 1999, 180, 61-70.
56. Koli, K.; Saharinen, J.; Hyytiainen, M.; Penttinen, C; Keski-Oja, J. Latency, activation, and binding proteins of TGF-beta. Microsc. Res. Tech., 2001, 52, 354-362.
57. Wang, H.; Kochevar, I.E. Involvement of UVB-induced reactive oxygen species in GF- beta biosynthesis and activation in keratinocytes. Free Radic. Biol. Med., 2005, 38, 890-897.
58. Chen, S.J.; Yuan, W.; Mori, Y.; Levenson, A.; Trojanowaska, M.; Varga, J. Stimulation of type I collagen transcription in human skin fibroblasts by TGF-P: involvement of Smad 3. J. Invest. Dermatol, 1999, 112, 49-57.
59. Quan, T.; He, T.; Voorhes, J.J.; Fisher, G.J. Ultraviolet irradiation blocks cellular responses to transforming growth factor-p by down-regulating its type-II receptor and inducing Smad7. J. Biol. Chem., 2001, 276, 26349-26356.
60. Quan, T.; He, T.; Kang, S.; Voorhees, J.J.; Fisher, G.J. Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-p type II receptor/Smad signaling. Am. J. Pathol, 2004, 165, 741-751.
61. Kaminska, B.; Wesolowska, A.; Danilkiewicz, M. TGF beta signaling and its role in tumour pathogenesis. Acta Biochim. Pol, 2005, 52, 329-337.
62. Mauviel, A.; Chung, K.; Agarwal, A.; Tamai, K.; Uitto, J. Cell-specific induction of distinct oncogenes of the jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor- β in fibroblasts and keratinocytes. J. Biol. Chem., 1996, 271, 10917-10923.
63. Philips, N. An anti TGF-P increased the expression of transforming growth factor- β, matrix metallproteinase-1, and elastin, and its effects were antagonized by ultraviolet radiation in epidermal keratinocytes. J. Dermatol. Sci., 2003, 33, 177-179.
64. Ashcroft, G.; Dodsworth, J.; VanBoxtel, E.; Tarnuzzer, R.; Horan, M.; Schultz, G.; Ferguson, M. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-p1 levels. Nat. Med., 1997, 3, 1209-1215.
65. Wu, J.; Chen, D.; Wu, Z. Quantitive study on the expression of mRNA for TGF-beta and collagenase (MMP-1), tissue metallopro-teinase inhibitor-1 (TIMP-1) in hypertrophic scar. Zhonghua Zheng Xing Wai Ke Za Zhi, 2000, 16, 34-36.
66. Edwards, D.R.; Leco, K.J.; Beaudry, P.P.; Atadja, P.W.; Veillette, C; Riabowol, K.T. Differential effects of transforming growth factor-beta 1 on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in young and old human fibroblasts. Exp. Gerantol, 1996, 31, 207-223.
67. Mori, Y.; Hatamochi, A.; Arakawa, M.; Ueki, H. Reduced Expression of mRNA for Transforming Growth Factor Beta (TGF beta) and TGF Beta R receptors I and II and Decreased TGF Beta Binding to the Receptors in Vitro-Aged Fibroblasts. Arch. Dermatol Res., 1998, 290, 158-162.
68. Zeng, G.; McCue, H.M.; Mastrangelo, L.; Millis, A.J. Endogenous TGF-beta activity is modified during cellular aging: effects on met-alloproteinase and TIMP-1 expression. Exp. Cell Res., 1996, 228, 271-276.
69. Gombau, L.; Garcia, F.; Lahoz, A.; Fabre, M.; Roda-Navarro, P.; Majano, P.; Alonso- Lebrero, J.L.; Pivel, J.P.; Castell, J.V.; Go-mez-Lechon, M.J.; Gonzalez, S. Polypodium leucotomos extract: Antioxidant activity and disposition. Toxicol. In Vitro, 2006, 20, 464-471.
70. Philips, N.; Smith, J.; Keller, T.; Gonzalez, S. Predominant effects of polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes. J. Dermatol. Sci., 2003, 32, 1-9.
71. Gomes, A.J.; Lunardi, C.N.; Gonzalez, S.; Tedesco, A.C. The antioxidant action of polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species. Braz. J. Med. Biol. Res., 2001, 34, 1487-1494.
72. Alonso-Lebrero, J.L.; Dominguez-Jimenez, C; Tejedor, R.; Brieva, A.; Pivel, J.P. Photoprotective properties of a hydrophilic extract of the fern polypodium leucotomos on human skin cells. J. Photo-chem. Photobiol, 2003, 70, 31-37.
73. Gombau, L.; García, F.; Lahoz, A.; Fabre, M.; Roda-Navarro, P.; Majano, P.; Alonso- Lebrero, J.L.; Pivel, J.P.; Castell, J.V.; Gómez-Lechon, M.J.; González, S. Polypodium leucotomos extract: antioxidant activity and disposition. Drugs Today, 2007, 43, 475-485.
74. ®) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: pathogenic relationships and therapeutic implications. Anticancer Res., 2000, 20, 1567-1576.
75. Bernd, A.; Ramirez-Bosca, A.; Huber, H.; Diaz-Alperi, J.; Thaci, D.; Sewell, A.; Auintanilla-Almagro, E.; Holzmann, H. In vitro studies on the immunomodulating effects of poloypodium leucotomos extract on human leukocyte fractions. Arzneimittelforschung, 1995, 45, 901-904.
76. Jahczyk, A.; Garcia-Lopez, M.A.; Fernandez-Peñas, P.; Alonso-Lebrero, J.L.; Benedicto, I.; López-Cabrera, M.; Gonzalez, S. A Polypodium leucotomos extract inhibits solar- simulated radiation-induced TNF-alpha and iNOS expression, transcriptional activation and apoptosis. Exp. Dermatol, 2007, 16, 823-829.
77. Rayward, J.; Villarrubia, V.G.; Guillen, C; Prieto, A.; Rodriguez-Zapata, M.; Sada, G.; Alvarez-Mon, M. An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro. Int. J. Immunopharmacol, 1997, 19, 9-14.
78. Alcaraz, M.V.; Pathak, M.A.; Rius, F.; Kollias, N.; Gonzalez, S. An extract of polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model. Pho-todermatol Photoimmunol Photomed, 1999, 15, 120-126.
79. Gonzalez, S.; Alonso-Lebrero, J.L.; Del Rio, R.; Jaen, P. Polypodium leucotomos extract: a nutraceutical with photoprotective properties. Drugs Today, 2007, 43, 475-485.
80. Middelkamp-Hup, M.A.; Pathak, M.A.; Parrado, C; Garcia-Caballero, T.; Rius-Diaz, F.; Fitzpatrick, T.B.; Gonzales, S. Orally administered polyodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin. J. Am. Acad. Dermatol, 2004, 50, 41-49.
81. Gambichler, T.; Skrygan, M.; Tomi, N.S.; Breuksch, S.; Altmeyer, P.; Kreuter, A. Significant downregulation of transforming growth factor-beta signal transducers in human skin following ultraviolet-A1 irradiation. Br J. Dermatol, 2007, 156, 951-956.
82. Quan, T.; He, T.; Kang, S.; Voorhees, J.J.; Fisher, G.J. Ultraviolet irradiation alters transforming growth factor beta/smad pathway in human skin in vivo. J. Invest. Dermatol, 2002, 119, 499-506.
83. Kim, H.H.; Cho, S.; Lee, S.; Kim, K.H.; Cho, K.H.; Eun, H.C.; Chung, J.H.J. Photoprotective and anti-skin-aging effects of eicos-apentaenoic acid in human skin in vivo. Lipid Res., 2006, 47, 921-930.
84. Capote, R.; Alonso-Lebrero, J.L.; Garcia, F.; Brieva, A.; Pivel, J.P.; Gonzalez, S. J. Polypodium leucotomos extract inhibits trans-urocanic acid isomerization and photodecomposition. Photochem. Photobiol, 2006, 82, 173-179.
85. Horvath, A.; Alvarado, F.; Szocs, J.; Alvarado, Z.N.; Padilla, G. Metablic effects of calagualine, an antitumoral saponine of polypodium leucotomos. Nature, 1967, 214, 1256-1258.
86. Nikolic, D.; Li, Y.; Chadwick, L.R.; Pauli, G.F.; Van Breemen, R.B. Metabolism of xanthohumol and isoxanthohumol, prenylated flavonoids from hops (Humulus lupulus L.), by human liver microsomes. J. Mass Spectrom., 2005, 40, 289-299.
87. Lee, S.H.; Kim, H.J.; Lee, J.S.; Lee, I.S.; Kang, B.Y. Inhibition of topoisomerase I activity and efflux drug transporters' expression by xanthohumol from hops. Arch. Pharm. Res., 2007, 30, 1435-1439.
88. Lemay, M.; Murray, M.A.; Davies, A.; Roh-Schmidt, H.; Randolph, R. In vitro and ex vivo cyclooxygenase inhibition by a hops extract. Asia Pac. J. Clin. Nutr., 2004, 13, S110.
89. Tripp, M.; Darland, G.; Lerman, R.; Lukaczer, D.; Bland, J.; Babish, J. Hop and Modified Hop Extracts have potent in vitro anti-inflammatory properties. Acta Hort, 2005, 668, 217-228.
90. Gerhauser, C; Alt, A.; Heiss, E.; Gamal-Eldeen, A.; Klimo, K.; Knauft, J.; Neumann, I.; Scherf, H.R.; Frank, N.; Bartsch, H.; Becker, H. Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop. Mol Cancer Ther., 2002, 1, 959-969
91. Noonan, M.; Benelli, R.; Albini, A. Angiogenesis and cancer prevention: a vision. Recent Results Cancer Res., 2007, 174, 219-224.
92. Colgte, E.C.; Miranda, C.L.; Stevens, J.F.; Bray, T.M.; Ho, E. Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits NF-kappaP activation in prostate epithelial cells. Cancer Lett, 2007, 246, 201-209.
93. Albini, A.; Dell'Eva, R.; Vené, R.; Ferrari, N.; Buhler, D.R.; Noonan, D.M.; Fassina, G. Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF- kappaB and Akt as targets. FASEB J., 2006, 20, 527-529.
94. Zhao, F.; Nozawa, H.; Daikonnya, A.; Kondo, K.; Kitanaka, S. Inhibitors of nitric oxide production from hops (Humulus lupulus L.). Biol. Pharm. Bull., 2003, 26, 61-65.
95. Overk, C.R.; Yao, P.; Chadwick, L.R.; Nikolic, D.; Sun, Y.; Cuen-det, M.A.; Deng, Y.; Hedayat, A.S.; Pauli, G.F.; Farnsworth, N.R.; van Breemen, R.B.; Bolton, J.L. Comparison of the in vitro estro-genic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J. Agric. Food Chem., 2005, 53, 6246-6253.
96. Effenberger, K.E.; Johnsen, S.A.; Monroe, D.G.; Spelsberg, T.C.; Westendorf, J.J. Regulation of osteoblastic phenotype and gene expression by hop-derived phytoestrogens. J. Steroid Biochem. Mol. Biol., 2005, 96, 387-399.
97. Monteiro, R.; Becker, H.; Azevedo, I.; Calhau, C. Effect of hop (Humulus lupulus L.) flavonoids on aromatase (estrogen synthase) activity. J. Agric. Food Chem., 2006, 54, 2938-2943.
98. Guerreiro, S.; Monteiro, R.; Martins, M.J.; Calhau, C.; Azevedo, I.; Soares, R. Distinct modulation of alkaline phosphatase isoenzymes by 17beta-estradiol and xanthohumol in breast cancer MCF-7 cells. Clin. Biochem., 2007, 40, 268-273.
99. Philips, N.; Devaney, J. Beneficial regulation of type I collagen and matrixmetalloproteinase -1 expression by estrogen, progesterone, and its combination in skin fibroblasts. J. Am. Aging Assoc., 2004, 26, 59-62.