Toshio Ichiba

Antihypertensive Effect of an Extract of Passiflora edulis Rind in Spontaneously Hypertensive Rats

Orally administered methanol extract of Passiflora edulis rind (10 mg/kg or 50 mg/kg) or luteolin (50 mg/kg), which is one of consistent polyphenols of the extract, significantly lowered systolic blood pressure in spontaneously hypertensive rats (SHRs). Quantitative analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that the extract contained 20 μg/g dry weight of luteolin and 41 μg/g dry weight of luteolin-6-C-glucoside. It also contained γ-aminobutyric acid (GABA, 2.4 mg/g dry weight by LC-MS/MS or 4.4 mg/g dry weight by amino acid analysis) which has been reported to be an antihypertensive material. Since the extract contained a relatively high concentration of GABA, the antihypertensive effect of the extract in SHRs might be due mostly to the GABA-induced antihypertensive effect and partially to the vasodilatory effect of polyphenols including luteolin.

New antioxidative phenolic glycosides isolated from Kokuto non-centrifuged cane sugar.

Nine compounds, 3-hydroxy-4,5-dimethoxyphenyl-β-D-glucopyranoside (1),β-D-fructfuranosyl-α-D-(6-vanilloyl)-glucopyranoside (2), β-D-fructfuranosyl-α-D-(6-syringyl)-glucopyranoside (3), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)- 2-methoxyphenoxy]propyl-β-D-glucopyranoside(4), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3- hydroxy-1-(E)-propenyl)-2,6-dimethoxyphenoxy] propyl-β-D-glucopyranoside (5), dehydrodiconiferyl alcohol-9′-β-D-glucopyranoside (6), 4-[ethane-2-[3-(4-hydroxy-3-methoxyphenyl)-2-propen]oxy]-2,6-dimethoxyphenyl-β-D-glucopyranoside (7), 4-[ethane-2-[3-(4-hydroxy-3-methoxyphenyl)-2-propen]oxy]-2-methoxyphenyl-β-D-glucopyranoside (8), and 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-2-[4-(3-hydroxy-1-(E)-propenyl)-2,6-dimethoxyphenoxy]propyl-β-D-glucopyranoside (9), were isolated from Kokuto non- centrifuged cane sugar. Their structures were elucidated by spectroscopic evidence, mainly based on the NMR technique. Among them, seven new glycosides were identified. The 2-deoxyribose oxidation method was used to measure their antioxidative activity. All of these compounds showed antioxidative activities.

New Phenolic Compounds from Kokuto, Non-centrifuged Cane Sugar

Five new phenolic compounds, 4-(β-D-glucopyranosyloxy)-3,5-dimethoxyphenyl-propanone (8), 3-[5-[(threo) 2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxybenzofurany]]-propanoic acid (12), 2-[4-(3-hydroxy-1-propenyl)-2,6-dimethoxyphenoxy]-3-hydroxy-3-(4-hydroxy-3,5-dimethoxyphenyl)propyl-β-D-glucopyranoside (13), 4-[(erythro) 2,3-dihydro-3(hydroxymethyl)-5-(3-hydropropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenyl-β-D-glucopyranoside (14), 9-O-β-D-xylopyranoside of icariol A2 (15), and known phenolic compounds were isolated from Kokuto, non-centrifuged cane sugar (Saccharum officinarum L.). Their structures were determined by a spectral investigation.

Luteolin Inhibits Endothelin-1 Secretion in Cultured Endothelial Cells

We discovered that luteolin, a typical flavonoid contained in various kinds of plants, inhibits the secretion and gene expression of endothelin-1 (ET-1), a potent vasoconstrictor regulating blood pressure, in porcine aortic endothelial cells. Its ED50 was about 10 μM. In addition, the inhibition of ET-1 by a glycoside compound of luteolin (luteolin-6-C-glucoside) was weak.

Castalagin and vescalagin purified from leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry: Dual inhibitory activity against PARP1 and DNA topoisomerase II

Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) is one of the most promising strategies for cancer chemotherapy, and a number of inhibitors possessing nicotinamide-like structures are being developed. To discover new types of PARP1 inhibitors, we screened a large number of substances of plant origin and isolated two inhibitory substances from the leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry. The inhibitory substances were identified as vescalagin and its epimer castalagin by analyses using nuclear magnetic resonance and mass spectrometry. The IC50 of purified vescalagin and castalagin for PARP1 inhibition were 2.67 and 0.86 μM, respectively. Unlike most of synthetic PARP1 inhibitors, castalagin showed a mixed type inhibition, of which Ki was 1.64 μM. When SH-SY5Y cells were treated with these ellagitannins at concentrations of less than 5 μM, cellular poly(ADP-ribosyl)ation was obviously attenuated. Castalagin and vescalagin also possessed inhibitory activity against DNA topoisomerase II, implying that they function as dual inhibitors in cells.