Yoshimi Oda

Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.

The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.

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.

Cucurbitacin E as a new inhibitor of cofilin phosphorylation in human leukemia U937 cells

Cucurbitane-type triterpenes, cucurbitacins B and E, were reported to exhibit cytotoxic effects in several cell lines mediated by JAK/STAT3 signaling. However, neither compound inhibited phosphorylation of STAT3 in human leukemia (U937) cells at low concentrations. We therefore synthesized a biotin-linked cucurbitacin E to isolate target proteins based on affinity for the molecule. As a result, cofilin, which regulates the depolymerization of actin, was isolated and suggested to be a target. Cucurbitacins E and I inhibited the phosphorylation of cofilin in a concentration-dependent manner, and their effective concentrations having the same range as the concentrations at which they had cytotoxic effects in U937 cells. In addition, the fibrous-/globular-actin ratio was decreased after treatment with cucurbitacin E in HT1080 cells. These findings suggested that the inhibition of cofilins phosphorylation increased the severing activity of cofilin, and then the depolymerization of actin was enhanced after treatment with cucurbitacin E at lower concentrations.

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.

Chemical structures of constituents from the whole plant of Bacopa monniera

Two new dammarane-type triterpene oligoglycosides, bacomosaponins A and B, and three new phenylethanoid glycosides, bacomosides A, B1, and B2, were isolated from the whole plant of Bacopa monniera Wettst. The chemical structures of the new constituents were characterized on the basis of chemical and physicochemical evidence. In the present study, bacomosaponins A and B with acyl groups were obtained from the whole plant of B. monniera. This is the first report of acylated dammarane-type triterpene oligoglycosides isolated from B. monniera. In addition, dammarane-type triterpene saponins significantly inhibited the aggregation of 42-mer amyloid β-protein.

New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition

The methanolic extract of Lawsonia inermis L. (henna) showed accelerative effects on nerve growth factor-induced neurite outgrowth in PC12 cells under non-fasting conditions. To elucidate the active constituents responsible for the neuronal differentiation, we conducted a search of the constituents and examined their accelerative effects on neurite outgrowth in PC12 cells. We isolated a new acetophenone glycoside, inermioside A, which exerted a significant accelerative effect on neurite outgrowth. We also confirmed the activities of nine known compounds, including quercetin and lalioside. In addition, we found that quercetin, one of the active constituents, increased Vav3 mRNA expression.

Structures of Aromatic Glycosides from the Seeds of Cassia auriculata

A new benzocoumarin glycoside, cassiaglycoside I (1), a new naphthol glycoside, cassiaglycoside II (2), a new chromon glycoside, cassiaglycoside III (3), a new phenylethyl glycoside, cassiaglycoside IV (4), were isolated from the seeds of Cassia auriculata, together with seven known constituents. The chemical structures of four new constituents were characterized on the basis of chemical and physicochemical evidence.