Glycosidic inhibitors of melanogenesis from leaves of Momordica charantia.

Eight glycosidic compounds, 1-8, including two new compounds, (4ξ)-α-terpineol 8-O-[α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside] (5) and myrtenol 10-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside] (7), were isolated from the BuOH-soluble fraction of a MeOH extract of Momordica charantia leaves. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-8 on the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), these compounds were found to exhibit inhibitory activities with 7.1-27.0% and 23.6-46.4% reduction of melanin content at 30 μM and 100 μM, respectively, with no or almost no toxicity to the cells (80.0-103.5% of cell viability at 100 μM). Western blot analysis showed that compound 7 reduced the protein levels of MITF, tyrosinase, TRP-1, and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on the α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2.

Kikuchi T ，Zhang J ，Huang Y ，Watanabe K ，Ishii K ，Yamamoto A ，Fukatsu M ，Tanaka R ，Akihisa T ... -  《-》

Melanogenesis-inhibitory activity of aromatic glycosides from the stem bark of Acer buergerianum.

A new benzyl glucoside, 3-O-demethylnikoenoside (1), along with eleven known compounds, including seven aromatic glycosides, 2-8, three lignans, 9-11, and one cyclitol, 12, were isolated from the BuOH-soluble fraction of a MeOH extract of Acer buergerianum stem bark. The structures of the new compound were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-12 on melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, i.e., hovetrichoside B (8), pinoresinol 4-O-β-D-glucopyranoside (9), and pinoresinol 4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (10), have been found to exhibit inhibitory effects with 41-49% melanin content compared to the control at 100 μM and low cytotoxicity to the cells (81-92% cell viability at 100 μM). Western blot analysis showed that compound 8 reduced the protein levels of MITF (=microphtalmia-associated transcription factor) and tyrosinase, in a concentration-dependent manner, suggesting that 8 inhibits melanogenesis in α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase. On the other hand, upon Western blotting, compound 9 was found to reduce the protein levels of tyrosinase and TRP-2, while it increased MITF and TRP-1 (=tyrosine-related protein 1), in a concentration-dependent manner, indicating that 9 inhibits melanogenesis in α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of tyrosinase and TRP-2.

Akihisa T ，Orido M ，Akazawa H ，Takahashi A ，Yamamoto A ，Ogihara E ，Fukatsu M ... -  《-》

Antioxidative and melanogenesis-inhibitory activities of caffeoylquinic acids and other compounds from moxa.

The MeOH extract of moxa, the processed leaves of Artemisia princeps PAMP. (Asteraceae), exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and melanogenesis-inhibitory activity in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Eight caffeoylquinic acids, 1 and 6-12, five flavonoids, 13-17, two benzoic acid derivatives, 18 and 19, three coumarin derivatives, 20-22, four steroids, 23-26, and six triterpenoids, 27-32, were isolated from the MeOH extract. Upon evaluation of compounds 1, 6-23, and four semisynthetic caffeoylquinic acid esters, 2-5, for their DPPH radical-scavenging activity, 15 compounds, 1-13, 17, and 19, showed potent activities (IC(50) 3.1-16.8 μM). The 15 compounds exhibited, moreover, potent inhibitory activities (51.1-92.5% inhibition) against peroxidation of linoleic acid emulsion at 10 μg/ml concentration. In addition, when 27 compounds, 1-8, 10, 12, 13, 15-18, 20-25, and 27-32, were evaluated for their inhibitory activity against melanogenesis in α-MSH-stimulated B16 melanoma cells, five caffeoylquinic acids, i.e., chlorogenic acid (1), ethyl chlorogenate (3), propyl chlorogenate (4), isopropyl chlorogenate (5), and butyl chlorogenate (6), along with homoorientin (17) and vanillic acid (18), exhibited inhibitory activities with 33-62% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (89-114% of cell viability at 100 μM). Western blot analysis showed that compound 6 reduced the protein levels of microphtalmia-associated transcription factor (MITF), tyrosinase, tyrosine-related protein 1 (TRP-1), and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2. Furthermore, four compounds, 13, 15, 16, and 30, exhibited cytotoxicities against HL60 human leukemia cell line (IC(50) 7.0-11.1 μM), and nine compounds, 14-16, 23, 26-28, 31, and 32, showed inhibitory effects (IC(50) 272-382 mol ratio/32 pmol 12-O-tetradecanoylphohrbol-13-acetate (TPA)) against Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA in Raji cells.

Akihisa T ，Kawashima K ，Orido M ，Akazawa H ，Matsumoto M ，Yamamoto A ，Ogihara E ，Fukatsu M ，Tokuda H ，Fuji J ... -  《-》

Glycosidic inhibitors of melanogenesis from leaves of Passiflora edulis.

A new flavonoid glycoside, chrysin 6-C-β-rutinoside (chrysin α-L-rhamnopyranosyl-(1→6)-C-β-glucopyranoside; 2), and two new triterpene glycosides, (31R)-31-O-methylpassiflorine (7) and (31S)-31-O-methylpassiflorine (8), along with 14 known glycosides, including three flavonoid glycosides, 1, 3, and 4, six triterpene glycosides, 5, 6, and 9-12, three cyano glycosides, 13-15, and two other glycosides, 16 and 17, were isolated from a MeOH extract of the leaves of Passiflora edulis (passion flower; Passifloraceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluation of compounds 1-17 against the melanogenesis in the B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, isoorientin (1), 2, and (6S,9R)-roseoside (17), exhibited inhibitory effects with 37.3-47.2% reduction of melanin content with no, or almost no, toxicity to the cells (90.8-100.2% cell viability) at 100 μM. Western blot analysis showed that compound 2 reduced the protein levels of MITF, TRP-1, and tyrosinase, in a concentration-dependent manner while exerted almost no influence on the level of TRP-2, suggesting that this compound inhibits melanogenesis on the α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of TRP-1 and tyrosinase. In addition, compounds 1-17 were evaluated for their inhibitory effects against the EpsteinBarr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.

Zhang J ，Koike R ，Yamamoto A ，Ukiya M ，Fukatsu M ，Banno N ，Miura M ，Motohashi S ，Tokuda H ，Akihisa T ... -  《-》

Melanogenesis inhibitory activity of monoterpene glycosides from Gardeniae Fructus.

A new iridoid glycoside, 10-O-(4"-O-methylsuccinoyl)geniposide (7), and two new pyronane glycosides, jasminosides Q and R (13 and 14, resp.), along with nine known iridoid glycosides, 1-6 and 8-10, and two known pyronane glycosides, 11 and 12, were isolated from a MeOH extract of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides (Rubiaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-14 on the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, i.e., 6-O-p-coumaroylgeniposide (3), 7, and 6'-O-sinapoyljasminoside (12), exhibited inhibitory effects with 21.6-41.0 and 37.5-47.7% reduction of melanin content at 30 and 50 μM, respectively, with almost no toxicity to the cells (83.7-106.1% of cell viability at 50 μM).

Akihisa T ，Watanabe K ，Yamamoto A ，Zhang J ，Matsumoto M ，Fukatsu M ... -  《-》