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

Abstract

Introduction !Melanin is a biopigment synthesized in melanosomes. Melanosomes enclosing melanin polymers are transferred from melanocytes to surrounding keratinocytes in the human epidermis. The color of human skin is determined primarily by the quantity, type, and distribution of melanin in keratinocytes [1,2]. Melanin has a critical role in the protection of the skin from solar ultraviolet (UV) radiation [3], but excess synthesis of melanin leads to hyperpigmentation disorders such as melasma, lentigo, and age spots [4]. Hence, the inhibitors of melanin biosynthesis have received considerable attention in clinical and cosmetic research, and melanin inhibitors such as hydroquinone [5], kojic acid [6,7], arbutin [8,9], and linoleic acid [10,11] have been discovered. "Sappan Lignum" is the heartwood of sappanwood (Caesalpinia sappan Linn.; Fabaceae) and is used both as a dyestuff and as an herbal medicine [12]. It has been used to treat wounds, skin diseases, leprosy, dysentery, menorrhagia, menoxenia, leukorrhea, and diabetic complications [13]. Several pharmacological studies have been undertaken focusing on the extracts and constituents of this plant as well as on the various activities found (e.g., immunomodulatory, . However, the effect on melanin synthesis of the extracts and constituents of this plant has not been studied in detail. In the present study, we investigated the inhibitory effects of the methanol (MeOH) extract of sappanwood on melanin synthesis in human melanoma HMV-II cells stimulated with forskolin. The MeOH extract showed inhibitory activity, and six compounds (one of which is novel) were isolated as active principles from the extract. Furthermore, the mechanism of action for the most potent inhibitory compound, brazilin 5, was investigated. 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-Omethylsappanol (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) (EC 50 : 3.0 ± 0.5 µM) and 4-O-methylsappanol (7) (EC 50 : 4.6 ± 0.7 µM) strongly suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate cytotoxicities against HMV-II cells with IC 50 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 influe...

Antioxidant and Tyrosinase Inhibitory Effects of Neolignan Glycosides from Crataegus pinnatifida Seeds

“…The above evidence suggested the presence of two C6-C3 units arising both from a neolignan and a glucose moiety, which was supported by analysis of the 13 C NMR, COSY, and HMBC spectra. One and two-dimensional NMR techniques (DEPT, COSY, HMQC, and HMBC) permitted assignments of all the 1 H and 13 C NMR signals for 1 (l " Table 1 and 2). The HMBC correlation peaks of H-8 and C-4′ and the anomeric proton resonance of glucose H-1′′ to C-9′ indicated that compound 1 was an 8-O-4′-neolignan-9′-glucopyranoside.…”

“…Melanin, the major pigment of skin, plays an important role in protecting it against the harmful effects of UV-irradiation. However, an increase in the levels of epidermal melanin synthesis and its uneven distribution can cause esthetic problems such as freckles, melasma, and aging spots [13]. Melanin synthesis is controlled by a cascade of enzymatic reactions.…”

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy

“…Currently, skin cleaning products are available on the market from macro-to nanosize containing both synthetic and natural products. 84,85 Research is being performed on several phyto-based nanocompounds for enhanced skin cleaning. Recently, phyto-based extracts used in cleansers showed enhanced skin cleansing activity by reducing pore size and skin oil content.…”

In vitro Antitubercular Activity of 3‐Deoxysappanchalcone Isolated From the Heartwood of Caesalpinia sappan Linn.

“…The heartwood of C. sappan has been used since ancient times as an ingredient in food and folk medicines against bacterial diseases and anemia and as a blood tonic (Tewtrakul et al, 2015;Nirmal et al, 2015). Many bioactive compounds have been derived from C. sappan, including phenolic compounds such as chalcones, protosappanin, brazilin, and homosioflavonoids (Jung et al, 2015;Mitani et al, 2013). 3-Deoxysappanchalcone is a naturally occurring chalcone compound isolated from C. sappan Linn.…”