Inhibitory effects of Zingiber officinale Roscoe derived components on aldose reductase activity in vitro and in vivo.

Ginger (Zingiber officinale Roscoe) continues to be used as an important cooking spice and herbal medicine around the world. Scientific research has gradually verified the antidiabetic effects of ginger. Especially gingerols, which are the major components of ginger, are known to improve diabetes including the effect of enhancement against insulin-sensitivity. Aldose reductase inhibitors have considerable potential for the treatment of diabetes, without increased risk of hypoglycemia. The assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy-3-methoxyphenyl)ethanol (2) and 2-(4-hydroxy-3-methoxyphenyl)ethanoic acid (3). Compounds 2 and 3 were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 +/- 1.9 and 18.5 +/- 1.1 microM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes but also lens galactitol accumulation in 30% of galactose-fed cataract rat model. A structure-activity relationship study revealed that the applicable side alkyl chain length and the presence of a C3 OCH3 group in the aromatic ring are essential features for enzyme recognition and binding. These results suggested that it would contribute to the protection against or improvement of diabetic complications for a dietary supplement of ginger or its extract containing aldose reductase inhibitors.

Studies on the constituents of Scutellaria species (XXII). Constituents of the roots of Scutellaria amabilis HARA.

From the roots of Scutellaria amabilis HARA, eleven new flavonoids, 5,7,2'-trihydroxy-8-methoxyflavone 7-O-beta-D-glucopyranoside, 5,7,2'-trihydroxy-8-methoxyflavone 2'-O-beta-D-glucopyranoside, 5,7-dihydroxy-8,2'-dimethoxyflavone 7-O-beta-D-glucopyranoside, 5,7,2'-trihydroxyflavone 2'-O-beta-D-glucopyranoside, 5,7,2',5'-tetrahydroxyflavone 7-O-beta-D-glucuronopyranoside, (2S)-5,7,2',5'-tetrahydroxyflavanone, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D-glucopyranoside, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D-glucuronopyranoside, (2S)-7,2'-dihydroxy-5-methoxyflavanone 7-O-beta-D-glucuronopyranoside, (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',II-5'-heptahydroxy-[I-6,II-6']-flavanonylflavone and (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',I-5',II-5'-octahydroxy-[I-6,II-6']-flavanonylflavone, were isolated, together with ten known flavonoids, wogonin (5,7-dihydroxy-8-methoxyflavone), 5,7-dihydroxy-8,2'-dimethoxyflavone, (2S)-5,7,2'-trihydroxyflavanone, scutevulin (5,7,2'-trihydroxy-8-methoxyflavone), 5,7,4'-trihydroxy-8-methoxyflavone, alpinetin ((2S)-7-hydroxy-5-methoxyflavanone), 5,7,2'-trihydroxyflavone, 5,7,2',5'-tetrahydroxyflavone, (2S)-7,2'-dihydroxy-5-methoxyflavanone and 5,7-dihydroxy-8,2'-dimethoxyflavone 7-O-beta-D-glucuronopyranoside. The structures were determined on the basis of chemical and spectral data.

Studies on nepalese crude drugs. XXVIII. Chemical constituents of Bhote Khair, the underground parts of Eskemukerjea megacarpum HARA.

From the underground parts of Eskemukerjea megacarpum HARA, two new stilbenes (14, 15) were isolated, together with a known coumarin, 5,7-dihydroxycoumarin (1), a tyramine derivative, trans-feruloyltyramine (2), two pyrogallol derivatives, gallic acid (3) and beta-glucogallin (4), four flavonoids, trifolin (5), hyperin (6), myricetin 3-O-beta-D-galactopyranoside (7), and myricitrin (8), five stilbenes, resveratorol (9), astringenin (10), piceid (11) astringin (12), and resveratorol 3-O-beta-D-(6-O-galloyl)glucopyranoside (13), a flavan-3-ol, (-)-epigallocatechin 3-O-gallate (16), two proanthocyanidins, catechin-(4alpha-->8)-epigallocatechin 3-O-gallate (17) and epicatechin 3-O-gallate-(4beta-->8)-epigallocatechin 3-O-gallate (18), and an anthocyanin, idaein (19). Compounds 14 and 15 were identified as (E)-3,5,3',4'-tetrahydroxystilbene 3-O-beta-D-(6-O-galloyl)glucopyranoside and (E)-3,5,4'-trihydroxystilbene 3-O-beta-D-(6-O-galloyl)glucopyranoside, respectively, based on spectral and chemical data.

Iminosugar-producing Thai medicinal plants.

Alpha-1-C-hydroxymethylfagomine (7), 3-O-beta-D-glucopyranosyl-DMDP (12), and 2,5-dideoxy-2,5-imino-D-glucitol (13) were isolated from the Thai traditional crude drug "Non tai yak" (Stemona tuberosa), which also contains a high concentration level of alpha-homonojirimycin (0.1% dry weight). "Thopthaep" (Connarus ferrugineus) and "Cha em thai" (Albizia myriophylla) contained 1-deoxymannojirimycin (DMJ) (10) at levels of 0.083% (dry weight) and 0.17% (dry weight), respectively. 2-O-alpha-D-Galactopyranosyl-DMJ (20), 3-O-beta-D-glucopyranosyl-DMJ (21), 1,4-dideoxymannojirimycin (17), 1,4-dideoxyallonojirimycin (18), and 1,4-dideoxyaltronojirimycin (19) from C. ferrugineus and 2-O-beta-D-glucopyranosyl-DMJ (22) and 4-O-beta-D-glucopyranosyl-DMJ (23) from A. myriophylla were isolated as new compounds.

Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in Scilla peruviana.

2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2-dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a search for glycosidase inhibitors in this family of plants, we isolated three new d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and 1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position, respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta-galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3-hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids 4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of 6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of bacterial beta-glucosidase with an IC(50) value of 5.1 microM.

New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.

Chromatographic separation of an extract of the bulbs of Scilla sibirica resulted in the isolation of five pyrrolidines, two pyrrolidine glycosides, six piperidines, one piperidine glycoside, and eight pyrrolizidines. 2,5-Dideoxy-2,5-imino-glycero-d-manno-heptitol (homoDMDP, 1) is a common alkaloid in all plants of the Hyacinthaceae examined to date and was also found in S. sibirica. The structures of the new alkaloids were elucidated by spectroscopic methods as 7-deoxy-homoDMDP (4), 2,5-dideoxy-2,5-imino-glycero-d-galacto-heptitol (5), the 4-O-beta-d-mannoside (6) and the 4-O-beta-d-mannobioside (7) of 6-deoxy-homoDMDP (2), 7-deoxyhomonojirimycin (12), 7-deoxyhomomannojirimycin (13), and polyhydroxypyrrolizidines, hyacinthacines A(4) (15), A(5) (16), A(6) (17), A(7) (18), B(4) (20), B(5) (21), and B(6) (22). HomoDMDP (1) is a potent inhibitor of beta-glucosidase and beta-galactosidase, while 6-deoxy-homoDMDP (2) showed significantly less inhibition. However, 7-deoxygenation of 1, leading to 4, showed no effect on the inhibitory activity toward both enzymes. Although 2 is not an inhibitor of alpha-l-fucosidase, the monomannoside of 2 shows inhibitory activity toward alpha-l-fucosidase. Elongation of the beta-mannopyranosyl chain of 6 to give 7 enhanced the inhibitory activity.

Effects of catechins on vascular tone in rat thoracic aorta with endothelium.

The effects of eight catechin derivatives on vascular tone in rat thoracic aorta were examined. Catechin derivatives (10 microM) potentiated the contractile response to phenylephrine in endothelium-intact arteries. The potentiations produced by EGCg and EGC were almost absent in endothelium-denuded arteries and abolished by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The catechin derivatives also inhibited endothelium-dependent relaxation in response to acetylcholine. The order of catechin derivatives ranked in terms of both increasing vascular reactivity and impairing endothelium-dependent relaxation was similar; (-)-gallocatechin (GC) >or= (-)-epigallocatechin (EGC) >or= (-)-gallocatechin gallate (GCg) >or= (-)-epigallocatechin gallate (EGCg) >or= (-)-catechin (C) >or= (-)-epicatechin (EC) >or= (-)-catechin gallate (Cg) >or= (-)-epicatechin gallate (ECg). In addition, EGC inhibited the endothelium-independent relaxation evoked by both sodium nitroprusside and NOC-7, a spontanous NO releaser, but EGCg inhibited only that by NOC-7. These findings indicate that catechin derivatives produce a potentiation of the contractile response and an inhibition of the vasorelaxant response, probably through inactivation of endothelium-derived nitric oxide (NO), and that the hydroxyl on C-5 of the B ring together with the stereoscopic structure between the C-3 group and the B ring of flavanols was of importance in mediating the above effects and that the substitution of a gallate group of C-3 attenuated the effects, probably due to a decreased response to solube guanylate cyclase in vascular smooth muscle cells.

New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii.

Chromatographic separation of the pod extract of Angylocalyx pynaertii resulted in the isolation of 13 sugar-mimic alkaloids (1-13). The structures of the new alkaloids were elucidated by spectroscopic methods as the 6-O-beta-D-glucoside (10) and N-hydroxyethyl derivative (11) of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (1), 1,6-dideoxynojirimycin (12), and 1,3,4-trideoxynojirimycin (13). 2,5-Imino-1,2,5-trideoxy-L-glucitol (7), 2,5-dideoxy-2,5-imino-D-fucitol (8), and beta-homofuconojirimycin (9), isolated from the pods as well as the bark, were very specific inhibitors of alpha-L-fucosidase with no significant inhibitory activity toward other glycosidases. In this work, 1,4-dideoxy-1,4-imino-D-ribitol (6) was found to be a better inhibitor of lysosomal beta-mannosidase than 2,5-imino-1,2,5-trideoxy-D-mannitol (2). N-Hydroxyethyl-1-deoxynojirimycin (miglitol), which is commercially available for the treatment of diabetes, retained its inhibitory potential toward rat intestinal maltase and sucrase, whereas 11 and the synthetic N-hydroxyethyl derivative of 2,5-dideoxy-2,5-imino-D-mannitol markedly lowered or abolished their inhibition toward all enzymes tested.