Tomoe Ohta

Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells.

Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (-)-lirinidine, and 2-hydroxy-1-methoxy-6a,7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine- and benzylisoquinoline-type alkaloids. In addition, 3-30 μM nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3-30 μM N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10-30 μM nuciferine inhibited the expression of TRP-2 mRNA.

Alkaloids from Sri Lankan curry-leaf (Murraya koenigii) display melanogenesis inhibitory activity: Structures of karapinchamines A and B

A methanolic extract and its ethyl acetate-soluble fraction from Sri Lankan curry-leaf, the leaves of Murraya koenigii, inhibited melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Two new carbazole alkaloids, karapinchamines A and B, were isolated from the ethyl acetate-soluble fraction together with 12 known carbazole alkaloids. The structures of karapinchamines A and B were determined by physicochemical analyses. The principal alkaloid constituents were found to display potent melanogenesis inhibitory activity. The structural requirements of the carbazole alkaloids for melanogenesis inhibitory activity were discussed.

Melanogenesis inhibitory and fibroblast proliferation accelerating effects of noroleanane- and oleanane-type triterpene oligoglycosides from the flower buds of Camellia japonica.

A 28-noroleanane-type triterpene oligoglycoside, camellioside E (4), an oleanane-type triterpene oligoglycoside, camellioside F (5), and the known compounds camelliosides A (1) and D (3) were isolated from a 50% EtOH extract of Camellia japonica flower buds from Korea. The principal constituents (1 and 5) significantly inhibited melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. Camellioside B (2), a major constituent of C. japonica grown in Japan, showed potent inhibition of melanogenesis [95.0 ± 1.0% (p < 0.01) at 20 μM]. The inhibitory effects of 1, 2, and 5 were stronger than that of the reference compound, arbutin. We believe the melanogenesis inhibitory effects of 2 and 5 are partly related to the proliferation inhibitory effects in B16 melanoma 4A5 cells. Conversely, camelliosides tended to enhance proliferation in normal human neonatal skin fibroblasts. Interestingly, camellioside B (2) significantly accelerated fibroblast proliferation. This biological selectivity could make camellioside B useful for treating skin disorders. Herein, we report the first scientific investigation of a triterpene that displays an inhibitory effect on melanogenesis, but that also has an enhancing effect on fibroblast proliferation.

Acylated sucroses and acylated quinic acids analogs from the flower buds of Prunus mume and their inhibitory effect on melanogenesis

The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang Province, China, showed an inhibitory effect on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. From the methanolic extract, five acylated sucroses, mumeoses A-E, and three acylated quinic acid analogs, 5-O-(E)-p-coumaroylquinic acid ethyl ester, and mumeic acid-A and its methyl ester, were isolated together with 13 known compounds. The chemical structures of the compounds were elucidated on the basis of chemical and physicochemical evidence. Inhibitory effects of the isolated compounds on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were also investigated. Acylated quinic acid analogs substantially inhibited melanogenesis. In particular, 5-O-(E)-feruloylquinic acid methyl ester exhibited a potent inhibitory effect [inhibition (%): 21.5±1.0 (P<0.01) at 0.1 μM]. Moreover, its biological effect was much stronger than that of the reference compound, arbutin [inhibition (%): 10.6±0.6 (P<0.01) at 10 μM]. Interestingly, the obtained acylated quinic acid analogs displaying melanogenesis inhibitory activity showed no cytotoxicity [cell viability >97% at 10 μM]. It is concluded that acylated quinic acid analogs are promising therapeutic agents for the treatment of skin disorders.

Lignan Dicarboxylates and Terpenoids from the Flower Buds of Cananga odorata and Their Inhibitory Effects on Melanogenesis

The methanolic extract from the flower buds of Cananga odorata showed an inhibitory effect on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extract, two new lignan dicarboxylates, canangalignans I and II, three new terpenoids, canangaterpenes I, II, and III, and eight known compounds were isolated. The structures of these compounds were elucidated on the basis of chemical/physicochemical evidence. Several mono- and sesquiterpene analogues significantly inhibited melanogenesis. In particular, canangaterpene I and (3R,3aR,8aS)-3-isopropyl-8a-methyl-8-oxo-1,2,3,3a,6,7,8,8a-octahydroazulene-5-carbaldehyde exhibited a potent inhibitory effect on melanogenesis [inhibition (%): 34.7±4.2 (p<0.01), 45.5±5.7 (p<0.01) at 1 μM, respectively] without inducing cytotoxicity. Moreover, the biological effect of these compounds was much stronger than that of the reference compound, arbutin. Thus, these isolated terpenoid derivatives may be promising therapeutic agents for the treatment of several skin disorders.

A rare glutamine derivative from the flower buds of daylily.

A rare glutamine derivative, hemerocallisamine I (1), was isolated from the methanolic extract of the flower buds of daylily, together with a new pyrrole alkaloid hemerocallisamine II (2) and a new γ-lactam derivative, hemerocallisamine III (3). The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. For hemerocallisamine I (1), the absolute configuration was determined by Mo-Kα X-ray crystallographic analysis. This is the first report of a glutamine derivative with a pyrrole ring from natural plants.

Diarylheptanoids with inhibitory effects on melanogenesis from the rhizomes of Curcuma comosa in B16 melanoma cells

The methanolic extract from the dried rhizomes of Curcuma comosa cultivated in Thailand was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extract, three new diarylheptanoids, diarylcomosols I-III, were isolated together with 12 known diarylheptanoids. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The diarylheptanoids inhibited melanogenesis, and several structural requirements of the active constituents for the inhibition were clarified. In particular, (3R)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol exhibited stronger inhibitory effect [IC50=0.36 μM] without inducing cytotoxicity. The biological effect was much stronger than that of a reference compound, arbutin [IC50=174 μM]. We conclude that diarylheptanoid analogs are promising therapeutic agents for the treatment of skin disorders.

Structures of acylated sucroses and an acylated flavonol glycoside and inhibitory effects of constituents on aldose reductase from the flower buds of Prunus mume

Five new acylated sucroses, mumeoses K–O, and a new acylated flavonol glycoside, mumeflavonoside A, were isolated from the flower buds of Prunus mume, cultivated in Zhejiang province, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated acylated sucroses and flavonol glycosides on aldose reductase were also investigated. Several flavonol glycosides including mumeflavonoside A were shown to inhibit aldose reductase.

Structure of constituents isolated from the flower buds of Cananga odorata and their inhibitory effects on aldose reductase

Three new terpenoid derivatives, canangaterpenes IV–VI, were isolated from the flower buds of Cananga odorata, cultivated in Thailand, together with eight known flavonoids. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Several terpenoid derivatives and flavonoids were shown to inhibit aldose reductase.

Chemical structures of constituents from the flowers of Osmanthus fragrans var. aurantiacus

Three new megastigmane glycosides named floraosmanosides I–III and a new γ-decalactone named floraosmanolactone I together with 16 known constituents were isolated from the flowers of Osmanthus fragrans var. aurantiacus cultivated in Guangxi Zhuang Autonomous Region, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. Among them, ligustroside and (+)-pinoresinol significantly inhibited nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages.