Suppression of Melanin Synthesis by the Phenolic Constituents of Sappanwood (Caesalpinia sappan)

Abstract

Sappanwood (Caesalpinia sappan Linn.) is used as an herbal medicine. It is sometimes used to treat skin damage or as a facial cleanser. In the present study, the methanol (MeOH) extract of sappanwood was found to inhibit melanin synthesis in cultured human melanoma HMV-II cells stimulated with forskolin, and six active compounds (1–5 and 7) were isolated from the extract along with a non-active compound (6). Compounds 2–7 were identified as sappanchalcone (2), 3′-deoxy-4-O-methylsappanol (3), brazilein, (4), brazilin (5), sappanol (6), and 4-O-methylsappanol (7). Compound 1 was a new compound, and its structure was determined to be (6aS,11bR)-7,11b-dihydro-6H-indeno[2,1-c]chromene-3,6a,10,11-tetrol by spectroscopic analyses. Among the six active compounds, brazilin (5) (EC₅₀: 3.0 ± 0.5 µM) and 4-O-methylsappanol (7) (EC₅₀: 4.6 ± 0.7 µM) strongly suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate cytotoxicities against HMV-II cells with IC₅₀ values of 83.1 ± 4.0 µM (for 2), 72.0 µM ± 2.4 (for 3), 33.8 ± 1.1 µM (for 4), 18.4 ± 0.8 µM (for 5), and 20.2 ± 0.8 (for 7), respectively. Brazilin (5) selectively suppressed the expression of mRNAs for tyrosinase-related protein (TYRP) 2 and tyrosinase but did not influence the expression of TYRP1. These results suggest that brazilin (5) is a new class of melanin inhibitor and that sappanwood could be used as a cosmetic material.

Key words

Caesalpinia sappan Linn. - Fabaceae - antimelanogenesis - brazilin - mRNAs expression

• References

• 1 Parvez S, Kang M, Chung HS, Cho C, Hong MC, Shin MK, Bae H. Survey and mechanism of skin depigmenting and lightening agents. Phytother Res 2006; 20: 921-934
• 2 Wakamatsu K, Kavanagh R, Kadekaro AL, Terzieva S, Sturm RA, Leachman S, Abdel-Malek Z, Ito S. Diversity of pigmentation in cultured human melanocytes is due to differences in the type as well as quantity of melanin. Pigment Cell Res 2006; 19: 154-162
• 3 Solano F, Briganti S, Picardo M, Ghanem G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res 2006; 19: 550-571
• 4 Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003; 16: 101-110
• 5 Jimbow K, Obata H, Pathak MA, Fitzpatrick TB. Mechanism of depigmentation by hydroquinone. J Invest Dermatol 1974; 62: 436-449
• 6 Mishima Y, Ohyama Y, Shibata T, Seto H, Hatae S. Inhibitory action of Kojic acid on melanogenesis and its therapeutic effect for various human hyper-pigmentation disorders. Skin Res 1994; 36: 134-150
• 7 Mishima Y, Hatta S, Ohyama Y, Inazu M. Induction of melanogenesis suppression: cellular pharmacology and mode of differential action. Pigment Cell Res 1988; 1: 367-374
• 8 Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 1996; 276: 765-769
• 9 Sugai T. Clinical effects of arbutin in patients with chloasma. Skin Res 1992; 34: 522-529
• 10 Ando H, Ryu A, Hashimoto A, Oka M, Ichihashi M. Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Arch Dermatol Res 1998; 290: 375-381
• 11 Ando H, Watabe H, Valencia JC, Yasumoto K, Furumura M, Funasaka Y, Oka M, Ichihashi M, Hearing VJ. Fatty acids regulate pigmentation via proteasomal degradation of tyrosinase: a new aspect of ubiquitin-proteasome function. J Biol Chem 2004; 279: 15427-15433
• 12 Sasaki Y, Suzuki M, Matsumoto T, Hosokawa T, Kobayashi T, Kamata K, Nagumo S. Vasorelaxant activity of sappan lignum constituents and extracts on rat aorta and mesenteric artery. Biol Pharm Bull 2010; 33: 1555-1560
• 13 Wu J, Hou B, Zhang MM, Zhou YP, Yu B. Protosappanin A, an immunosuppressive constituent from a Chinese herb, prolongs graft survival and attenuates acute rejection in rat heart allografts. Transplant Proc 2008; 40: 3719-3722
• 14 Ye M, Xie WD, Lei F, Meng Z, Zhao YN, Su H, Du LJ. Brazilein, an important immunosuppressive component from Caesalpinia sappan L. Int Immunopharmacol 2006; 6: 426-432
• 15 Hu CM, Liu YH, Cheah KP, Li JS, Lam CSK, Yu WY, Choy CS. Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide. J Ethnopharmacol 2009; 121: 79-85
• 16 Badami S, Moorkoth S, Rai SR, Kannan E, Bhojraj S. Antioxidant activity of Caesalpinia sappan heartwood. Biol Pharm Bull 2003; 26: 1534-1537
• 17 Parameshwar S, Srinivasan KK, Rao CM. Oral antidiabetic activities of different extracts of Caesalpinia bonducella seed kernels. Pharm Biol 2002; 40: 590-595
• 18 Rodriguez-Lopez V, Salazar L, Estrada S. Spasmolytic activity of several extracts obtained from some Mexican medicinal plants. Fitoterapia 2003; 74: 725-728
• 19 Wang YZ, Sun SQ, Zhou YB. Extract of the dried heartwood of Caesalpinia sappan L. attenuates collagen-induced arthritis. J Ethnopharmacol 2011; 136: 271-278
• 20 Namikoshi M, Nakata H, Saitoh T. Homoisoflavonoids from Caesalpinia sappan . Phytochemistry 1987; 26: 1831-1833
• 21 Namikoshi M, Nakata H, Saitoh T. Homoisoflavonoids and related compounds. V. A novel dibenzoxocin derivative from Caesalpinia sappan L. Chem Pharm Bull 1987; 35: 3615-3619
• 22 Kim DS, Baek NI, Oh SR, Jung KY, Lee IS, Lee HK. NMR assignment of brazilein. Phytochemistry 1997; 46: 177-178
• 23 Hulme AN, McNab H, Peggie DA, Quye A. Negative ion electrospray mass spectrometry of neoflavonoids. Phytochemistry 2005; 66: 2766-2770
• 24 Fu LC, Huang XA, Lai ZY, Hu YJ, Liu HJ, Cai XL. A new 3-benzylchroman derivative from sappan lignum (Caesalpinia sappan). Molecules 2008; 13: 1923-1930
• 25 Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Inhibitory effects of α-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Biol Pharm Bull 2004; 27: 510-514
• 26 Kawabata T, Cui MY, Hasegawa T, Takano F, Ohta T. Anti-inflammatory and anti-melanogenic steroidal saponin glycosides from Fenugreek (Trigonella foenum-graecum L.) seeds. Planta Med 2011; 77: 705-710
• 27 Bhatnagar V, Srirangam A, Abburi R. In vitro modulation of proliferation and melanization of melanoma cells by citrate. Mol Cell Biochem 1998; 187: 57-65
• 28 Matsuda H, Kawaguchi Y, Yamazaki M, Hirata N, Naruto S, Asanuma Y, Kaihatsu T, Kubo M. Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf extract and its lignan constituents. Biol Pharm Bull 2004; 27: 1611-1616
• 29 DʼOrazio JA, Nobuhisa T, Cui R, Arya M, Spry M, Wakamatsu K, Igras V, Kunisada T, Granter SR, Nishimura EK, Ito S, Fisher DE. Topical drug rescue strategy and skin protection based on the role of Mc1 r in UV-induced tanning. Nature 2006; 443: 340-344
• 30 Busca R, Ballotti R. Cyclic AMP: a key messenger in the regulation of skin pigmentation. Pigment Cell Res 2000; 13: 60-69
• 31 Callender VD, St Surin-Lord S, Davis EC, Maclin M. Postinflammatory hyperpigmentation: etiologic and therapeutic considerations. Am J Clin Dermatol 2011; 12: 87-99
• 32 Tatsuno T, Jinno M, Arima Y, Kawabata T, Hasegawa T, Yahagi N, Takano F, Ohta T. Anti-inflammatory and anti-melanogenic proanthocyanidin oligomers from peanut skin. Biol Pharm Bull 2012; 35: 909-916
• 33 Lee MH, Lin YP, Hsu FL, Zhan GR, Yen KY. Bioactive constituents of Spatholobus suberectus in regulating tyrosinase-related proteins and mRNA in HEMn cells. Phytochemistry 2006; 67: 1262-1270