INHIBITION OF MELANIN CONTENT BY PUNICALAGINS 453 (3) M. Nakagawa, K. Kawai, and K. Kawai, Contact allergy to kojic acid in skin care products, Contact Dermatitis, 32, 9–13 (1995). (4) N. Smit, J. Vicanova, and S. Pavel, The hunt for natural skin whitening agents, Int. J. Mol. Sci., 10, 5326–5349 (2009). (5) V. A. Evreinoff, Le grenadier, Fruits d’Outre-Mer, 4, 161–170 (1949). (6) R. F. Wang, W. D. Xie, Z. Zhang. D. M. Xing, Y. Ding, W. Wang, and L. J. Du, Bioactive compounds from the seeds of Punica granatum (Pomegranate), J. Nat. Prod., 67, 2096–2098 (2004). (7) T. B. Machado, I. C. R. Leal, A. C. F. Amaral, K. R. N. Dos Santos, G. Marlei, M. G. da Silva, and R. M. Kuster, Antimicrobial ellagitan nin of Punica granatum fruits, J. Brazilian Chem. Soc., 13, 606–610 (2002). (8) M. Aviram, L. Dornfeld, M. Rosenblat, N. Volkova, M. Kaplan, R. Coleman, T. Hayek, D. Presser, and B. Fuheman, Pomegranate juice consumption reduces oxidative stress, atherogenic modifi cations to LDL, and platelet aggregation: Studies in humans and in atherosclerotic apolipoprotein E-defi cient mice, Am. J. Clin. Nutr., 71, 1062–1076 (2000). (9) B. Fuhrman, N. Volkova, and M. Aviram, Pomegranate juice inhibits oxidized LDL uptake and choles- terol biosynthesis in macrophages, J. Nutr. Biochem., 16, 570–576 (2005). (10) M. Larrosa, F. A. Tomás-Barberán, and J. C. Espin, The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochon- drial pathway, J. Nutr. Biochem., 17, 611–625 (2006). (11) T. M. Li, G. W. Chen, C. C. Su, J. G. Lin, C. C. Yeh, J. G. Chung, and K. C. Cheng, Ellagic acid induced p53/p21 expression, G1 arrest and apoptosis in human bladder cancer T24 cells, Anticancer Res., 25, 971–979 (2005). (12) H. Shimogaki, Y. Tanaka, H. Tamai, and M. Masuda, In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition, Int. J. Cosmet. Sci., 22, 291–303 (2000). (13) I. Ertam, B. Mutlu, I. Unal, S. Alper, B. Kivcak, and O. Ozer, Effi ciency of ellagic acid and arbutin in melasma: A randomized, prospective, open-label study. J. Dermatol., 35, 570–574 (2008). (14) N. Akhtar, R. Parveeen, B. A. Khan, M. Jamshaid, and H. Khan, Development of skin-friendly derma- tological water-in-oil emulsion of pomegranate juice, Proc. Pak. Acad. Sci., 49, 269–278 (2012). (15) M. Yoshimura, Y. Watanabe, K. Kasai, J. Yamakoshi, and T. Koga, Inhibitory effect of an ellagic acid- rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation, Biosci. Biotechnol. Biochem., 69, 2368–2373 (2005). (16) S. Rout and R. Banerjee, Free radical scavenging, anti-glycation and tyrosinase inhibition properties of a polysaccharide fraction isolated from the rind from Punica granatum, Bioresour. Technol., 98, 3159–3163 (2007). (17) G. Diwakar, J. Rana, and J. D. Scholten, Inhibition of melanin production by a combination of Siberian larch and pomegranate fruit extracts, Fitoterapia, 83, 989–995 (2012). (18) D. C. Bennett, P. J. Cooper, and I. R. Hart, A line of non-tumerogenic melanocytes, syngeneic with B16 melanoma and requiring a tumor promoter for growth, Int. J. Cancer, 39, 414–418 (1987). (19) L. Ni-Komatsu, J. K. Leung, D. Williams, J. Min, S. M. Khersonsky, Y. T. Chang, and S. J. Orlow, Triazine-based tyrosinase inhibitors identifi ed by chemical genetic screening, Pigment Cell Res., 18, 447–453 (2005). (20) N. P. Seeram, L. S. Adams, S. M. Henning, Y. Niu, Y. Zhang, M. G. Nair, and D. Heber, In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegran- ate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice, J. Nutr. Biochem., 16, 360–367 (2005). (21) V. M. Virador, N. Kobayashi, J. Matsunaga, and V. J. Hearing, A standardized protocol for assessing regulators of pigmentation, Anal. Biochem., 270, 207–219 (1999). (22) B. Cerdá, R. Llorach, J. J. Cerón, J. C. Espín, and F. A. Tomás-Barberán, Evaluation of the bioavailabil- ity and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice, Eur. J. Nutr., 42, 18–28 (2003). (23) D. Heber, “Pomegranate Ellagitannins,” in Herbal Medicine: Biomolecular and Clinical Aspects, F. F. Benzie and S. Wachtel-Galor. Eds. (CRC Press, Boca Raton, FL, 2011), Chapter 10. (24) S. Parvez, M. Kang, H. S. Chung, C. Cho, M. C. Hong, M. K. Shin, and H. Bae, Survey and mechanism of skin depigmenting and lightening agents, Phytother. Res., 20, 921–934 (2006). (25) J. Rana and G. Diwakar, Topical composition with skin lightening effect, US patent 7897184 B1 (2012). (26) J. Rana and G. Diwakar, Topical composition with skin lightening effect, US patent 8202556 B2 (2012).