A. INCISUS EXTRACT AND WRINKLE REDUCTION 323 previous study reported the effects of the crude extract of A. incisus’s heartwood on tyros- inase, melanogenesis, and oxidation activities. Therefore, this study focused on the ability of the extract to improve the functions of fi broblasts from wrinkled-skin biopsies. These functions include cell proliferation, type I procollagen and MMP-1 production, and the capacity to reorganize collagen fi bers. We found that the aged-related decrease in the functional activities of fi broblasts from wrinkles could be reversible by treatment with the extract from A. incisus’s heartwood. However, these fi ndings on cell-culture fi broblasts do not prove that the extract will decrease wrinkles in humans. Clinical studies in human subjects will be needed to determine the effi cacy of the extract on wrinkle reduction. ACKNOWLEDGMENTS Financial and facility support from the Thailand Research Fund and the Center of Excel- lence for Innovation in Chemistry (PERCH-CIC), Commission on Higher Education, Ministry of Education is gratefully acknowledged. In addition, we thank Dr. Charles Norman Scholfi eld for his valuable discussions. REFERENCES (1) P. U. Giacomoni and G. Rein, A mechanistic model for the aging of human skin, Micron, 35, 179–184 (2004). (2) V. N. Novoseltsev, J. Novoseltseva, and A. Yashin, A homeostatic model of oxidative damage explains paradoxes observed in the earlier aging experiments: A fusion and extension of older theories of aging, Biogerontology, 2, 127–138 (2001). (3) D. Batisse, R. Bazin, T. Baldeweck, B. Querleux, and J.-L. Lévêque, Infl uence of age on the wrinkling capacities of the skin, Skin Res. Technol., 8, 148–154 (2002). (4) S. Diridollou, V. Vabre, M. Berson, L. Vaillant, D. Black, J. M. Lagarde, J. M. Grégoire, Y. Gall, and F. Patat, Skin aging: Changes of physical properties of human skin in vivo, Int. J. Cosmet. Sci., 23, 353–362 (2001). (5) J. H. Chung, J. Y. Seo, H. R. Choi, M. K. Lee, C. S. Youn, G. Rhie, K. H. Cho, K. H. Kim, K. C. Park, and H. C. Eun, Modulation of skin collagen metabolism in aged and photoaged human skin in vivo, J. Invest. Dermatol., 117, 1218–1224 (2001). (6) J. Varani, D. Spearman, P. Perone, S. E. G. Fligiel, S. C. Datta, Z. Q. Wang, Y. Shao, S. Kang, G. J. Fisher, and J. J. Voorhees, Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin and by collagenase-degraded collagen in vitro, Am. J. Pathol., 158, 931–942 (2001). (7) E. F. Bernstein and J. Uitto, The effect of photodamage on dermal extracellular matrix, Clin. Dermatol., 14, 143–151 (1996). (8) G. Jenkins, Molecular mechanisms of skin aging, Mech. Aging Dev., 123, 801–810 (2002). (9) J. Varani, R. L. Warner, M. Gharaee-Kermani, S. H. Phan, S. Kang, J. H. Chung, Z. Q. Wang, S. C. Datta, G. J. Fisher, and J. J. Voorhees, Vitamin A antagonizes decreased cell growth and elevated collagen- degrading matrix metalloproteinases and stimulates collagen accmulation in naturally aged human skin, J. Invest. Dermatol., 114, 480–486 (2000). (10) M. D. West, The cellular and molecular biology of skin aging. Arch. Dermatol., 130, 87–95 (1994). (11) M. Jouandeaud, C. Viennet, S. Bordes, B. Closs, and P. Humbert, Comparison of the biomechanical and biosynthetics behavior of normal human fi broblasts and fi broblasts from a forehead wrinkle, IFSCC Magazine, 7, 109–113 (2004). (12) E. Tamariz and F. Grinnell, Modulation of fi broblast morphology and adhesion during collagen matrix remodeling, Mol. Biol. Cell, 13, 3915–3929 (2002). (13) H. U. Püschel, J. Chang, P. K. Müller, and J. Brickmann, Attachment of intrinsically and extrinsically aged fi broblasts on collagen and fi bronectin, J. Photochem. Photobiol. B, 27, 39–46 (1995). (14) H. S. Talwar, C. E. M. Griffi ths, G. J. Fisher, T. A. Hamilton, and J. J. Voorhees, Reduced type I and type II procollagens in photodamaged adult human skin, J. Invest. Dermatol., 105, 285–290 (1995).

JOURNAL OF COSMETIC SCIENCE 324 (15) A. M. Kligman, D. Dogadkina, and R. M. Lavker, Effects of topical tretinoin on non-sun-exposed pro- tected skin of the elderly, J. Am. Acad. Dermatol., 29, 25–33 (1993). (16) J. S. Weiss, C. N. Ellis, J. T. Headington, T. Tincoff, T. A. Hamilton, and J. J. Voorhees, Topical tretinoin improves photoaged skin: A double blind, vehicle-controlled study, JAMA, 259, 527–532 (1988). (17) A. M. Kligman, G. L. Grove, R. Hirose, and J. J. Leyden, Topical tretinoin for photoaged skin, J. Am. Acad. Dermatol., 15, 836–859 (1986). (18) B. V. Nusgens, P. Humbert, A. Rougier, A. C. Colige, M. Haftek, C. A. Lambert, A. Richard, P. Creidi, and C. M. Lapiere, Topically applied vitamin C enhances the mRNA level of collagen I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis, J. Invest. Dermatol., 116, 853–859 (2001). (19) G. J. Fisher, Z.-Q. Wang, S. C. Datta, J. Varani, S. Kang, and J. J., Voorhees, Pathophysiology of prema- ture skin aging induced by ultraviolet light, N. Eng. J. Med., 337, 1419–1428 (1997). (20) P. Donsing, N. Limpeanchob, and J. Viyoch, Evaluation of the effect of Thai breadfruit’s heartwood extract on melanogenesis-inhibitory and antioxidation activities, J. Cosmet. Sci., 59, 41–58 (2008). (21) K. Shimizu, R. Kondo, and K. Sakai, The skin-lightening effects of artocarpin on UVB-induced pig- mentation, Planta Med., 68, 79–81 (2002). (22) K. Shimizu, R. Kondo, K. Sakai, S.-H. Lee, and H. Sato, The inhibitory components from Artocarpus incisus on melanin biosynthesis, Planta Med., 64, 408–412 (1998). (23) E. Bell, S. Stephanie, B. Hull, C. Merrill, S. Rosen, A. Chamson, D. Asselineau, L. Dubertret, B. Coulomb, C. Lapiere, B. Nusgens, and. Y. Neveux, The reconstitution of living skin, J. Invest. Dermatol., 81, 2s–10s (1983). (24) E. Bell, B. Ivarssen, and C. Merrill, Production of a tissue-like structure by contraction of collagen lat- tices by human fi broblasts of different proliferative potential in vitro, Proc. Natl. Acad. Sci. USA, 76, 1274–1278 (1979). (25) T. Pitaksuteepong, A. Somsiri, and N. Waranuch, Targeted transfollicular delivery of artocarpin extract from Artocarpus incisus by means of microparticles, Eur. J. Pharm. Biopharm., 67, 639–645 (2007). (26) C. Vinnet, V. Armbruster, A. C. Gabiot, T. Gharbi, J. Bride, and P. Humbert, Comparing the contrac- tile properties of human fi broblasts in leg ulcers with normal fi broblasts, J. Wound Care, 13, 358–361 (2004). (27) R. M. Lavker, Structural alterations in exposed and unexposed skin, J. Invest. Dermatol., 73, 59–66 (1979). (28) H. Watanabe, T. Shimizu, J. Nishihira, R. Abe, T. Nakayama, M. Taniguchi, H. Sabe, and T. Ishibashi, Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by macrophage migration inhibitory factor (MIF) in human dermal fi broblasts, J. Biol. Chem., 279, 1676–1683 (2004). (29) M. Brennan, H. Bhatti, K. C. Nerusu, N. Bhagavathula, S. Kang, G. J. Fisher, J. J. Voorhees, and J. Varani, Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin, Photochem. Photobiol., 78, 43–48 (2003). (30) J. Campisi, Replicative senescence: An old wives tale, Cell, 84, 497–500 (1996). (31) A. J. Millis, M. Hoyle, H, M. McCue, and H. Martini, Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fi broblasts, Exp. Cell Res., 211, 90–98 (1992). (32) L. Rakic, C. M. Lapiere, and B. V. Nusgens, Comparative caustic and biological activity of trichloroacetic acid and glycolic acid on keratinocytes and fi broblasts in vitro, Skin Pharmacol. Appl. Skin Physiol., 13, 52–59 (2000). (33) H. K. Kleinman, M. L. McGarvey, and G. R. Martin, Role of endogenous collagen synthesis in the adhesion of human skin fi broblasts, Cell Biol. Int. Rep., 6, 591–599 (1982).