Munehisa Arisawa

Inhibition of lens aldose reductase by flavonoids

Abstract The inhibitory activities of 73 flavonoids against rat aldose reductase were systematically investigated and cosmosiin, luteolin-7-glucuronide, lonicerin, 6-hydroxyluteolin, kaempferol-3-rhamnoside and avicularin were newly found to be highly active. The degree of inhibition appears to depend on the solvent system used. In general flavones are more active than flavonols and flavanones, glycosides are more active than aglycones, and the number of sugars present affects the activity.

Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice.

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.

a-glucosidase Inhibitors From Paraguayan Natural Medicine, Ñangapiry, The Leaves Of Eugenia Uniflora

The water-soluble extract from a Paraguayan natural medicine, Nangapiry, the leaves of Eugenia uniflora L. (Myrtaceae), which has been used as an antidiabetic agent, was found to show inhibitory activities on the increase of plasma glucose level in the sucrose tolerance test (STT) conducted with mice. The portion adsorbed on a cation exchange resin was also found to inhibit a-glucosidases. From the active portion, two new active compounds named uniflorines A ( 1 ) and B ( 2 ) and known (+)-(3a, 4a, 5ß)-1-methylpiperidine-3, 4, 5-triol ( 3 ) were isolated. The structures of uniflorines A and B were determined as (-)-(1S, 2R, 6S, 7R, 8R, 8aR)-1,2,6,7,8–pentahydroxyindolizidine and (+)-(1S, 2R, 5R, 7R, 8S, 8aS)-1,2,5,7,8-pentahydroxyindolizidine by spectral means, respectively.

Cancer chemopreventive effects of constituents of Caesalpinia ferrea and related compounds.

The anti-tumor promoting effects of fruits of Caesalpinia ferrea MART. (Leguminosae) were tested by the in vitro Epstein-Barr virus early antigen (EBV-EA) activation assay, and its active constituents were identified as gallic acid (1) and methyl gallate (2). A total of 49 related compounds of 1 and 2 were analysed for the effects by this assay, and the structure activity relationships have been proposed. Three acetophenone derivatives, 2,6-dihydroxyacetophenone (48), 2,3,4-trihydroxyacetophenone (50) and 2,4,6-trihydroxy- acetophenone (51) were found to show potent inhibitory activity.

Scopadulcic acid-A and -B, new diterpenoids with a novel skeleton, from a Paraguayan crude drug “typychá kuratũ” (scoparia dulcis L.)

Abstract Scopadulcic acid-A and -B, diterpenoids with a novel skeleton, have been isolated from the whole plants of Scopari dulcis L., and their structures, including the absolute configuration, were determined based on the 2-D NMR and CD spectral data.

Dihydroxynortropane alkaloids from calystegine-producing plants

Three dihydroxynortropanes, 2alpha,7beta-dihydroxynortropane, 2alpha,3beta-dihydroxynortropane, and 3alpha,7beta-dihydroxynortropane, were isolated from calystegine-producing plants in the families Convolvulaceae and Solanaceae. 2alpha,7beta-Dihydroxynortropane was isolated from six species in the Convolvulaceae whereas only Calystegia soldanella contained it and 2alpha,3beta-dihydroxynortropane. Although neither of these were detectable in three species tested in the Solanaceae, 3alpha,7beta-dihydroxynortropane was, however, isolated from Duboisia leichhardtii.

Inhibition of HIV-reverse transcriptase activity by some phloroglucinol derivatives

Four phloroglucinol derivatives, named mallotophenone (5‐methylene‐bis‐2,6‐dihydroxy‐3‐methyl‐4‐methoxyacetophenone), mallotochromene (8‐acetyl‐5,7‐dihydroxy‐6‐(3‐acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐2,2‐dimethylchromene), mallotojaponin (3‐(3,3(dimethylallyl)S‐(3(acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐phloracetophenone) and mallotolerin (3‐(3‐methyl‐2‐hydroxybut‐3‐enyl)‐5‐(3‐acetyl‐2,4‐dihydroxy‐5‐methyl‐6‐methoxybenzyl)‐phloracetophenone), have been tested for their ability to inhibit the activity of human immunodeficiency virus (HIV)‐reverse transcriptase. Under the reaction conditions with (rA)n · (dT)12–18 as the template · primer, the enzyme activity was inhibited by approximately 70% in the presence of 10 μ/ml mallotochromene or mallotojaponin, whereas mallotophenone and mallotolerin were much less inhibitory to the enzyme. The enzyme activity was also inhibited, though to lesser extent, by these compounds under similar conditions with initiated MS‐2 phage RNA as the template · primer, The mode of inhibition was, as analyzed with mallotojaponin, competivite with respect to the template · primer, (rA)n · (dT)12–18, and non‐competitive with respect to the triphosphate substrate, dTTP, The K i value of mallotojaponin for HIV‐reverse transcriptase was determined to be 6.1 μM.

Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae).

2,6-Dideoxy-7-O-(beta-D-glucopyranosyl) 2,6-imino-D-glycero-L-gulo- heptitol (7-O-beta-D-glucopyranosyl-alpha-homonojirimycin, 1) was isolated from the 50% methanol extract of the whole plant of Lobelia sessilifolia (Campanulaceae), which was found to potently inhibit rice alpha-glucosidase. Adenophorae radix, roots of Adenophora spp. (Campanulaceae), yielded new homonojirimycin derivatives, adenophorine (2), 1-deoxyadenophorine (3), 5-deoxyadenophorine (4), 1-C-(5-amino-5-deoxy-beta-D-galactopyranosyl)butane (beta-1-C-butyl-deoxygalactonojirimycin, 5), and the 1-O-beta-D-glucosides of 2 (6) and 4 (7), in addition to the recently discovered alpha-1-C-ethylfagomine (8) and the known 1-deoxymannojirimycin (9) and 2R,5R-bis(hydroxymethyl)-3R,4R- dihydroxypyrrolidine (DMDP, 10). Compound 4 is a potent inhibitor of coffee bean alpha-galactosidase (IC50 = 6.4 microM) and a reasonably good inhibitor of bovine liver beta-galactosidase (IC50 = 34 microM). Compound 5 is a very specific and potent inhibitor of coffee bean alpha-galactosidase (IC50 = 0.71 microM). The glucosides 1 and 7 were potent inhibitors of various alpha-glucosidases, with IC50 values ranging from 1 to 0.1 microM. Furthermore, 1 potently inhibited porcine kidney trehalase (IC50 = 0.013 microM) but failed to inhibit alpha-galactosidase, whereas 7 was a potent inhibitor of alpha-galactosidase (IC50 = 1.7 microM) without trehalase inhibitory activity.

8-Hydroxytricetin 7-glucuronide, a β-glucuronidase inhibitor from Scoparia dulcis

Abstract A new flavone glycoside has been isolated from Scoparia dulcis together with 11 known compounds. The new glycoside was determined as 5,7,8,3′,4′,5′-hexahydroxyflavone glucuronide by spectral analysis. The new glycoside and isovitexin showed inhibitory activity against β-glucuronidase.

Paeonilactone-A, -B, and -C, new monoterpenoids from paeony root

Three new monoterpenoids named paeonilactone-A, -B, and -C were isolated from Paeony root (roots of Paeonia albiflora PALLAS var. trichocarpa BUNGE) and their structures were determined to be 2, 3, and 4, respectively, by means of chemical and spectroscopic studies.