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I Nishioka

Publications and source records attributed to I Nishioka.

At least 19 recordsLinked to original sources
PubMed2001

Revised structure of cercidinin A, a novel ellagitannin having (R)-hexahydroxydiphenoyl esters at the 3,4-positions of glucopyranose.

The structure of cercidinin A, an ellagitannin isolated from the bark of Cercidiphyllum japonicum, was revised to 1,2,6-tri-O-galloyl-3,4-(R)-hexahydroxydiphenoyl-beta-D-glucose by two-dimensional NMR spectral analysis. Cercidinin A represents the first ellagitannin possessing a hexahydroxydiphenoyl group at the 3,4-positions of a modified 4C1-glucopyranose core.

Carboxylic Ester Hydrolases↗
PubMed1998

Study on the inhibitory effect of tannins and flavonoids against the 1,1-diphenyl-2 picrylhydrazyl radical.

Fifty-one tannins and forty-one flavonoids isolated from Oriental medicinal herbs were evaluated for their antioxidant ability with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system. The results showed that tannins and certain flavonoids are potential free-radical scavengers, and that their activity against the DPPH radical is closely associated with their chemical structure. A comparison of the two classes of compounds showed that tannins have more potential than flavonoids because almost all the tannins demonstrated significant scavenging action within a low concentration range, whereas the activity of flavonoids varied distinctively among the different compounds. An increase of galloyl groups, molecular weight, and ortho-hydroxyl structure enhanced the activity of tannins, whereas the number and position of hydroxyl groups were important features for the scavenging of free radicals by flavonoids. Moreover, it appeared that when the free hydroxyl group was methoxylated or glycosylated, the inhibitory activity was obviously decreased or even abolished.

Bepridil↗
PubMed1997

Magnesium lithospermate B suppresses the increase of active oxygen in rats after subtotal nephrectomy.

Subtotally nephrectomized rats were found to have decreased activities of superoxide dismutase (SOD) and catalase, and spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that the amount of hydroxyl radical in the residual kidney tissue was greater than that in normal rat kidney. This indicated both direct and indirect involvement of free radicals in renal failure. In contrast, rats given magnesium lithospermate B (10 mg/kg body weight) orally for 30 days after subtotal nephrectomy showed restoration of SOD and catalase activities to almost normal levels. Hydroxyl radical, which is highly reactive and for which there is no scavenger system in the body, was decreased markedly in kidney homogenates obtained from rats given magnesium lithospermate B and in an experimental system for hydroxyl radical production to which magnesium lithospermate B was directly added. The increased levels of uremic toxins in the blood were also low in rats given magnesium lithospermate B. This indicates that magnesium lithospermate B helps to inhibit the progression of renal failure by scavenging radicals.

Administration, Oral↗
PubMed1995

Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses.

Previously we have isolated the quaternary base alkaloids, magnoflorine and phellodendrine, from Phellodendri Cortex (cortex of Phellodendron amurense Rupr., Rutaceae) as the biologically active principles to suppress local graft-versus-host (GvH) reactions in mice. In this paper, we focus on phellodendrine. Phellodendrine suppressed local semisyngeneic GvH reactions and systemic allogeneic GvH reactions in X-ray irradiated recipient mice. Phellodendrine also suppressed the induction phase of sheep red blood cell (SRBC)-induced delayed type hypersensitivity in mice and tuberculin-induced delayed type hypersensitivity in guinea pigs, but did not suppress the effector phase of these reactions. Surprisingly, phellodendrine, unlike prednisolone and cyclophosphamide, did not affect antibody production in mice to SRBC. Phellodendrine was expected to be a valuable new type of immunosuppressor against the cellular immune response.

Animals↗
PubMed1995

Effects of a Dan Shen component, magnesium lithospermate B, in nephrectomized rats.

Magnesium lithospermate B, a compound newly isolated from Dan Shen, was given orally to rats for 70 days after excision of five-sixths of their kidney volume. As a result, mesangial proliferation, tubulo-interstitial lesions and glomerular sclerotic lesions, which were conspicuous in rats that were not given magnesium lithospermate B after nephrectomy, were inhibited. Furthermore, a decrease in blood urea nitrogen, improvement of hypoproteinemia, hypoalbuminemia and hypercholesteremia, and inhibition of urinary protein excretion were observed. The levels of creatinine, methylguanidine and guanidino-succinic acid, which accumulate in the blood with the progress of renal failure, were decreased significantly in rats given magnesium lithospermate B. These results indicate that magnesium lithospermate B, a component of an Oriental medicine has potential as a new therapeutic agent for inhibiting the progression of renal dysfunction.

Animals↗
PubMed1994

Inhibition of collagen hydroxylation by lithospermic acid magnesium salt, a novel compound isolated from Salviae miltiorrhizae Radix.

We have screened several chinese medicinal herbs for the presence of antifibrotic agents. An aqueous extract of Salviae miltorrhizae Radix was found to inhibit collagen secretion by human skin fibroblasts without affecting DNA or noncollagen protein synthesis. We have subsequently purified the material exhibiting the inhibitory activity and identified it as magnesium lithospermate. From its chemical structure this compound was predicted to be an inhibitor of the post-translational modifying enzymes prolyl and lysyl hydroxylases in collagen biosynthesis. Accordingly, it decreased the extent of prolyl and lysyl hydroxylations in collagen by approx. 50%. Added to cell extracts it inhibited both prolyl and lysyl hydroxylase activities, but only lysyl hydroxylase activity when added to intact cells. Oral administration of this compound to mice led to a significant reduction of prolyl hydroxylation in newly-synthesized skin collagen. This naturally-occurring compound thus offers a potential means for treating fibrotic diseases, such as systemic scleroderma and keloid.

Animals↗
PubMed1994

Principle of the bark of Phellodendron amurense to suppress the cellular immune response.

We previously reported that Wen-Qing-Yin (Unsei-in), a traditional Chinese blended medicine, inhibited the induction phase of various kinds of delayed type hypersensitivity (DTH) and local graft-versus-host (GvH) reactions, but did not affect humoral immune responses or the effector phase of DTH in experimental animals. In another report, we demonstrated that Phellodendri Cortex (bark of Phellodendron amurense Rupr. Rutaceae) was a component having the most potent suppressive effect on the cellular immune response among the 8 medical plants composing Unsei-in. In the present study, we isolated OB-1 and OB-5 from Phellodendri Cortex as the biologically active principles to suppress local GvH reactions in mice. OB-1 and OB-5 are quaternary base alkaloids known as magnoflorine and phellodendrine, respectively. They suppressed the local GvH reaction, when given i.p. to the host mice at 5-20 mg/kg for 8 consecutive days from the day of spleen cell transfer to cause the reaction. Both OB-1 and OB-5 suppressed picryl chloride-induced delayed type hypersensitivity (PC-DTH) when given i.p. to mice at 10 and 20 mg/kg for 5 consecutive days from the day of the sensitization, but did not suppress it when given at the time of the challenge. These results suggest that OB-1 and OB-5 suppress the induction phase but not the effector phase of the cellular immune response. They are expected to have a value as a new type of immunosuppressor.

Analysis of Variance↗
PubMed1993

Tannins as potent inhibitors of DNA topoisomerase II in vitro.

Fifty-two out of 60 tannins, including gallo-, ellagi-, condensed, and complex tannins, are inhibitors of human DNA topoisomerase II in vitro. Thirty-six compounds that completely inhibited enzyme activity at a concentration of 500 nM or less, as assessed by ATP-dependent unknotting of P4 phage DNA, were at least 100-fold more potent than the clinically useful antitumor agent etoposide (VP-16). Relative inhibitory activity was primarily related to the number of phenolic hydroxyl groups (galloyl and hexahydroxydiphenoyl moieties) found in the active structures, with more groups generally conferring increased potencies. Unlike VP-16 and some DNA intercalative agents that stabilize the topoisomerase II-DNA cleavage intermediate, none of the active compounds induced protein-linked DNA breaks in cultured cells. Some of the tannins reduced VP-16-induced protein-linked DNA breaks by 20% or more, but one of these compounds, (-)-epicatechin, was not an inhibitor in vitro. Our data suggest that some tannins, such as sangiin H-6, that are potent inhibitors of catalytic double DNA-strand passage in vitro may target intracellular enzyme activity in a similar fashion to known poisons that interfere with formation of the enzyme-DNA covalent intermediate.

DNA↗
PubMed1993

Inhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis.

Many tannins were previously identified as candidate topoisomerase poisons. Here we report further studies on sanguiin H-6, a dimeric ellagitannin isolated from Sanguisorba officinalis as an inhibitor of DNA topoisomerases. Catalytic strand-passing activities of topoisomerases I and II were inhibited in vitro with IC50 values of 1 microM and 0.01 microM, respectively. This inhibition was not associated with stabilization of covalent enzyme-DNA complexes but rather by a mechanism preventing formation of such covalent intermediates, as measured by interference with drug-induced cleavage in vitro. The IC50 values for topoisomerase I-DNA complexes induced by camptothecin and with topoisomerase II-DNA complexes induced by VP-16 were 0.02 microM and 0.16 microM, respectively. Pre-incubation studies followed by drug-dilution revealed that the in vitro inhibitory effects of sanguiin H-6 were irreversible, and for topoisomerase I, the test compound prevented enzyme-DNA interaction as seen by shifts in mobility on agarose gels. By measuring interference with drug-induced protein-linked DNA breaks in isolated HeLa nuclei, inhibition of topoisomerases I and II on a natural chromatin template was demonstrated with IC50 values of 5 microM and > 10 microM, respectively. Sanguiin H-6 inhibited HeLa cell growth with an ED50 of 12 microM and also interfered in a dose-dependent fashion with intracellular topoisomerase activities but with lower potencies than those observed using subcellular assay systems. Based on these studies, sanguiin H-6 could be broadly classified as a type of poison which does not stimulate the formation of cleavable-complexes, with intracellular activity but without any marked selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Catalysis↗
PubMed1993

Inhibitory effects of tannins on NADH dehydrogenases of various organisms.

We examined the effects of purified tannins and related compounds (33 species) on NADH-ubiquinone-1 oxidoreductase activity in four kinds of organism (Paracoccus denitrificans, Bacillus subtilis, Photobacterium phosphoreum, and Thermus thermophilus HB-8) and rat liver mitochondria. In addition to pentagalloylglucose, which was reported as a potent inhibitor of NADH dehydrogenases (NDH), sanguiin H-11, oolonghomobisflavan A, and polymerized procyanidin are potent inhibitors for both types of NDH (NDH-1 and NDH-2). We found that some other tannins contained in tea are also inhibitors of NDH from all organisms.

Animals↗
PubMed1993

Tannins and related compounds. CXXII. New dimeric, trimeric and tetrameric ellagitannins, lambertianins A-D, from Rubus lambertianus Seringe.

Chemical examination of the leaves of Rubus lambertianus Seringe (Rosaceae) has led to the isolation of four new ellagitannins, which were characterized on the basis of chemical and spectroscopic evidence to be dimers [lambertianins A (6) and B (7)], a trimer [lambertianin C (8)] and a tetramer [lambertianin D (10)], all having sanguisorbic acid ester group(s) as linking unit(s) between glucopyranose moieties. Furthermore, HPLC analyses of fifteen Rubus species collected in Japan and Taiwan revealed that the trimer (8) and the tetramer (10), together with sanguiin H-6 (1), occur widely in these species.

Chromatography, High Pressure Liquid↗
PubMed1993

Effects of rhubarb tannins on renal function in rats with renal failure.

The effects of tannins purified from Rhei Rhizoma on various parameters of renal function were investigated in rats with adenine-induced renal failure. The glomerular filtration rate, renal plasma flow and renal blood flow were significantly increased in rats given (-)-epicatechin 3-O-gallate at a dose of 5 or 10 mg/kg body weight/day for 24 days. Administration of 5 mg of procyanidin B-2 3,3'-di-O-gallate also led to a significant increase in renal functional parameters. However, unlike the former two components, procyanidin C-1 3,3',3''-tri-O-gallate caused aggravation of renal function.

Adenine↗
PubMed1993

Effect of magnesium lithospermate B on the renal and urinary kallikrein activities in rats with adenine-induced renal failure.

A study was conducted to examine the effect of magnesium lithospermate B on both the urinary and renal total and active kallikrein and prokallikrein in rats with adenine-induced renal failure. In rats given magnesium lithospermate B at a dose of 10 mg/kg body weight/day for 12 days, significant increases of urinary total and active kallikrein were associated with significant increases of urine volume and urinary total and active kallikrein were associated with significant increases of urine volume and urinary creatinine excretion. The renal total and active kallikrein levels were also significantly elevated by the treatment with magnesium lithospermate B. On day 24, the urinary excretion of total and active kallikrein and prokallikrein was significantly increased. Concomitantly, a significant increase in renal kallikrein (total, active and pro-) was found in the rats given magnesium lithospermate B. A significant relationship existed between the urinary creatinine and active kallikrein excretion. These results suggest that magnesium lithospermate B may stimulate the synthesis of kallikrein and/or conversion to active kallikrein, thus improving renal function.

Adenine↗
PubMed1992

Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents.

Fifty-seven tannins and related compounds, including gallotannins, ellagitannins, and condensed and complex tannins, were evaluated for their cytotoxicities against human tumor cell lines, including malignant melanoma, lung carcinoma, ileocecal adenocarcinoma, epidermoid carcinoma, malignant melanoma, and medulloblastoma cell lines. Among them, chebulagic acid [1], geraniin [2], sanguiin H-11 [3], 4,5-di-O-galloylquinic acid [12], 1,3,4,5-tetra-O-galloylquinic acid [15], 1(beta)-O-galloylpedunculagin [24], furosin [29], castalagin [38], sanguiin H-2 [34], vescalagin [39], grandinin [40], phyllyraeoidin A [42], (-)-epicatechin 3-O-gallate [50], cinnamtannin B2 [55], and acutissimin A [56] exhibited moderate selective cytotoxicity against PRMI-7951 melanoma cells with ED50 values in the range of 0.1-0.8 microgram/ml. Selective cytotoxicities against the melanoma cells were also observed for strictinin [22], pedunculagin [23], eugeniin [25], elaeocarpusin [28], punicacortein C [37], casuarinin [41], sanguiin H-6 [43], procyanidin B-2 3,3'-di-O-gallate [51], procyanidin C-1 3,3',3"-tri-O-gallate [52], and cinnamtannin B1 [54] with ED50 values of 1-4 micrograms/ml. All of the tannins were found to be inactive (greater than 10 micrograms/ml) against lung carcinoma (A-549), ileocecal adenocarcinoma (HCT-8), epidermoid carcinoma of nasopharnyx (KB), and medulloblastoma (TE-671) tumor cells.

Antineoplastic Agents, Phytogenic↗
PubMed1992

Effect of magnesium lithospermate B in rats with sodium-induced hypertension and renal failure.

To evaluate the antihypertensive effect of magnesium lithospermate B isolated from Salviae miltiorrhizae radix, determinations of blood pressure and urinary excretions of sodium, potassium, prostaglandin E2 (PGE2) and kallikrein, which have been proposed to play an important role in the regulation of blood pressure, were made in rats with sodium-induced hypertension and renal failure. In rats given magnesium lithospermate B, blood pressure was significantly decreased, whereas urinary excretion of electrolytes was significantly increased. Urinary PGE2 excretion following administration of magnesium lithospermate B increased as the dose of the compound was stepped up. The activity of kallikrein in urine was also increased by the treatment. From these results, the blood pressure-lowering action of magnesium lithospermate B may be due in part to enhancement of the kallikrein-prostaglandin system.

Animals↗
PubMed1991

Augmentation of renal response by magnesium lithospermate B.

Magnesium lithospermate B and adenine were given simultaneously to rats p.o. in order to investigate their renal effects. In rats given magnesium lithospermate B at a dose of 5 mg/kg body weight/day for 12 or 24 days, glomerular filtration rate, renal plasma flow and renal blood flow were increased significantly. A significant increase in renal function parameters was also found in rats given 10 mg of magnesium lithospermate B. Urinary excretion of prostaglandin E2 was increased by administration of magnesium lithospermate B, while those of 6-keto-prostaglandin F1 alpha and thromboxane B2 were unaffected at a dose of 5 mg or 10 mg/kg body weight/day for 12 or 24 days. The activity of kallikrein in urine increased markedly and significantly in rats given 5 or 10 mg of magnesium lithospermate B for 12 or 24 days. From these results, it seems that magnesium lithospermate B increases renal function by improving the renal circulatory state through activation of kallikrein and promotion of prostaglandin E2 production.

Administration, Oral↗