Biomedical subjects
Publications and source records attributed to Hideyuki Ito.
Six aliphatic acid amides (1-6) were isolated from the pericarp of Zanthoxylum piperitum fruits. MS and NMR spectroscopic investigation revealed that these compounds have a ketone and/or hydroxyl group(s) in the unsaturated aliphatic acid moiety of the structure of the amides. Combinations 3-4 and 5-6 are stereoisomers in terms of the relative configurations of their two asymmetric carbons.
A novel dimeric flavonol glycoside linked through a methylene group, kunzeagin A (1), and six new chromone C-glucosides, kunzeachromones A-F (2-7), were isolated along with seven known compounds from the leaf extract of Kunzea ambigua. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical properties. Kunzeachromones A-F provided additional examples of galloylated C-glucosidic chromones occurring in the Myrtaceae. Kunzeagin A (1) and major constituents of this plant (6-C- and 8-C-glucosylchromones and their monogallates) exhibited potent inhibitory effects on activation of Epstein-Barr virus early antigen induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.
Helicobacter pylori is a major etiological agent in gastroduodenal disorders. In this study, we isolated 36 polyphenols and 4 terpenoids from medicinal plants, and investigated their antibacterial activity against H. pylori in vitro. All hydrolyzable tannins tested demonstrated promising antibacterial activity against H. pylori. Monomeric hydrolyzable tannins revealed especially strong activity. Other compounds demonstrated minimal antibacterial activity with a few exceptions. A monomeric hydrolyzable tannin, Tellimagrandin I demonstrated time- and dose-dependent bactericidal activity against H. pylori in vitro. On the other hand, hydrolyzable tannins did not affect the viability of MKN-28 cells derived from human gastric epithelium. Hydrolyzable tannins, therefore, have potential as new and safe therapeutic regimens against H. pylori infection. Furthermore, we investigated effects of hydrolyzable tannins on lipid bilayer membranes. All the hydrolyzable tannins tested demonstrated dose-dependent membrane-damaging activity. However, it remains to be elucidated whether their membrane-damaging activity directly contributes to their antibacterial action.
Two new additional trijugin-type limonoids, sandrapins D (4) and E (5), which are analogues of the previously reported sandrapins A-C (1-3), were isolated as minor components from the leaves of Sandoricum koetjape (Meliaceae), and their structures were elucidated on the basis of MS and NMR spectral data.
We established callus cultures of the monocotyledonous plants Kniphofia foliosa and K. tuckii (Asphodelaceae), which produce the anthraquinone derivatives chrysophanol and its glycosides. The minor product chrysophanol 8-O-beta-gentiobioside was fully characterized by spectroscopic analysis and synthesis.
Various canine breeds are remarkably different from each other not only in their sizes and shapes but also in behavioral traits, suggesting that some of them are under genetic control. Although dopaminergic neurotransmission system is considered to affect animal behavior, little is known about related genes in canine. Relations between specific alleles in polymorphic regions of the dopamine receptor D4 gene (DRD4) and personality or psychiatric disorders have been reported in humans, and we first found polymorphism in exon III region of the gene in 4 canine breeds. In this study we surveyed allele frequency distribution in 23 breeds including a total of 1,535 unrelated individuals. In exon III, 8 alleles including a novel allele were identified. A group of breeds in which the alleles 447b, 498 and 549 were frequent tended toward high scores in aggression-related behavioral traits than that with frequent alleles 435 and 447a. Moreover, a polymorphism based on 24 bp insertion/deletion was found in exon I region for the first time in dogs. This information may be of use for candidate gene studies of behavioral variation in dogs.
The treatment of seven cases of thymic carcinoma is reported. According to the Masaoka classification of the disease, there were five cases of stage III and two of stage IVb. Five were identified histopathologically as squamous cell carcinoma, one as undifferentiated carcinoma, and one as small cell neuroendocrine carcinoma. Surgery was performed during the course of chemotherapy and radiotherapy in 5 cases, and in 2, the organs infiltrated by neoplastic cells were partially excised together. Radiotherapy was performed as adjuvant therapy in one case of partial excision. In another case, after six years of chemotherapy and radiotherapy that yielded a partial response (PR), cancerous infiltration of the chest wall occurred, and partial removal of the chest wall became necessary. After the remaining case showed a PR to chemotherapy, complete macroscopic excision of the tumor was undertaken, but mediastinal lymph gland metastasis was present, and so radiotherapy was also initiated. In two cases, surgery was not performed. One of these was treated with chemotherapy alone, the other, only with radiotherapy. The mean survival period of the five patients who died as a result of their tumors was 44.8 months. One of the two who survived for over four years had squamous cell carcinoma, the other, undifferentiated carcinoma. The case of small cell neuroendocrine carcinoma was assessed as having a PR, and so complete extraction of the thymic neoplasm was carried out, and followed with radiotherapy. This patient is still alive.
The lung ball is a special type of pulmonary aspergillosis (PA) occurring often after chemotherapy for leukemia. Histologically the ball, with air crescent sign on roentgenogram, is compatible with necrotizing lung tissue admixed with Aspergilli. The lung ball differs entirely from the common "fungus ball" in its quality, though they are similar in roentgenological appearances. The present two cases were leukemia which showed pulmonary findings in their therapeutic course, resulting in lung resection. In both cases the lung ball was confirmed histopathologically. Immunostaining of the lung tissue for neutrophil elastase showed elastase in various sites in the bronchial wall, pulmonary blood vessels (artery, vein) and cavitary wall. In our previous studies, much importance was attached to the disturbance of the pulmonary circulation caused by fibrin deposition as a factor in the developmental course of the fungus ball type aspergillosis (semi-invasive type). The circulatory disturbance of the lung was recognized also in the present cases. This two-way destruction of the pulmonary tissue, resulting from both neutrophil elastase activities and pulmonary circulatory disturbances, were regarded as the most important factor for the development of the lung ball. There are few studies on aspergillar lung ball with regard to the above respects.
The gastroprotective effects of 70% acetone extracts of Quercus suber and Quercus coccifera leaves and of tannins (pedunculagin, castalagin, phillyraeoidin A, and acutissimin B) purified from these extracts were examined in the mouse using the ethanol-induced gastric ulcer model. Both extracts (25, 50, and 100 mg/kg), given orally, prevented the formation of ethanol-induced lesions in the stomach. The percent protection varied between 68 and 91%. Purified tannins (50 mg/kg) were also effective in protecting the stomach against ethanol, and the percent protection varied from 66 to 83%. Castalagin was the most potent. Both extracts and all of the tannins tested (10, 25, and 50 microg/mL) strongly inhibited (55-65%) the lipid peroxidation of rabbit brain homogenate. These results suggest that the gastroprotective effects of extracts of Q. suber and Q. coccifera leaves and the purified tannins in this experimental model are related to their anti-lipoperoxidant properties.
Three hydrolyzable tannins, glansrins A-C, together with adenosine, adenine, and 13 known tannins were isolated from the n-BuOH extract of walnuts (the seeds of Juglans regia L.). Glansrins A-C were characterized as ellagitannins with a tergalloyl group, or related polyphenolic acyl group, based on spectral and chemical evidence. The 14 walnut polyphenols had superoxide dismutase (SOD)-like activity with EC(50) 21.4-190 microM and a remarkable radical scavenging effect against 1,1-diphenyl-2-picrylhydrazyl (DPPH) (EC(50) 0.34-4.72 microM).
Three trijugin-type limonoids, sandrapins A, B and C, were isolated from the leaves of Sandoricum koetjape and their structures, which are related to capensolactones, were elucidated by a detailed 2D-NMR spectroscopic analysis.
Tannins and lignins are natural compounds contained in plants such as tea leaves. Previously, we demonstrated that tannic acid represses 12-o-tetra-decanoyl phorbol-13-acetate (TPA)-induced human immunodeficiency virus (HIV) promoter activity. Furthermore, we demonstrated that a 30-bp element located just downstream of the NF-kappaB element in the HIV promoter responds negatively to tannic acid. However, the kinds of molecules responsible for this suppressive effect have remained unknown, because tannic acid is a mixture of various galloylglucoses. Here, we examined structure-defined natural compounds for HIV promoter-suppressive effects. We found that ellagitannins suppress TPA-induced HIV promoter activity to the same extent as tannic acid. 3-phenylcoumarins, isoflavone and chalcones have more suppressive effects than ellagitannins. On the other hand, other flavonoids and acetogenins have no suppressive effect. 3-phenylcoumarins and chalcones showed no suppressive effect on the cytomegalovirus (CMV) promoter, suggesting that they act specifically on the HIV promoter. These results suggest that 3-phenylcoumarin or chalcone compounds could be used to develop novel anti-HIV drugs with an action targeted at HIV promoter activity.
After bioassay-guided fractionation of the extract from Sandoricum koetjape bark, which exhibited significant toxicity to killifish (Oryzias latipes), two ichthyotoxic triterpenoids were isolated and characterized as koetjapic acid and 3-oxo-olean-12-en-29-oic acid. These constituents, along with non-toxic katonic acid, had a remarkable inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA), which is a preliminary in vitro screening method for possible anti-tumor-promoting agents. Of the triterpenoids active in vitro, koetjapic acid appears to be a promising cancer chemopreventive agent, since it significantly delayed tumor promotion in two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz(a)anthracene and promoted by TPA.
Four minor components, along with the major cyanogenic glycosides, amygdalin and prunasin, were isolated from Prunus persica seeds (Persicae Semen; Tounin), and characterized as mandelic acid glycosides (beta-gentiobioside and beta-D-glucoside) and benzyl alcohol glycosides (beta-gentiobioside and beta-D-glucoside). The anti-tumor promoting activity of these compounds was examined in both in vitro and in vivo assays. All of the compounds significantly inhibited the Epstein-Barr virus early antigen activation induced by tumor promoter. In addition, they produced a delay of two-stage carcinogenesis on mouse skin that was comparable in potency to (-)-epigallocatechin gallate from green tea. Structure-activity relationships indicated that a substituent at the benzylic position with glycosidic linkage affected the in vitro and in vivo activities with an order of enhancing potency, CN<COOH<H.
A number of avian species are difficult to sex morphologically, especially as nestlings. Like other avian species, many species of Falconiformes are sexually monomorphic. Therefore, it is desirable that new methods based on DNA analysis are established in Falconiformes and other sexual monomorphic species. We identified sex in Falconiformes by two alternative methods. First, we used a sexing method based on the intronic length variation between CHD1W and CHD1Z using primers flanking the intron. In this method, two species of Falconidae could be identified for sexing. However, six species of Accipitridae could not, because they have few length variations. The second method used was based on differences in sequences between CHD1W and CHD1Z. From sequence analysis, a 3'-terminal mismatch primer on point mutation conserved among Falconiformes was designed, and identification of sex with the amplification refractory mutation system (ARMS) was performed. This method could identify sex in all species tested. In addition, because the 3'-terminal mismatch primer was designed on a point mutation conserved among Falconiformes, ARMS with these primers may identify sex in all Falconiformes. These are simple and rapid sexing methods, since only polymerase chain reaction (PCR) and agarose electrophoresis are required. In conclusion, sex identification by an alternative PCR approach based on intronic length variation and on differences in sequences between CHD1W and CHD1Z proved applicable to and useful for Falconiformes.
In a search for possible antitumor agents from natural sources, megastigmane glycosides and polyphenolic constituents isolated from the leaves of Eriobotrya japonica (Rosaceae) were found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced activation of Epstein-Barr virus early antigen in Raji cells. Roseoside and procyanidin B-2 were among the active compounds found in an in vitro assay; these compounds were further assessed for antitumor activity in vivo in a two-stage carcinogenesis assay on mouse skin. Roseoside significantly delayed carcinogenesis induced by peroxynitrite (initiator) and TPA (promoter), and its potency was comparable to that of a green tea polyphenol, (-)-epigallocatechin 3-O-gallate, in the same assay.
Oenotherin T(1) was isolated from leaves of Oenothera tetraptera as a major ellagitannin. Its structure, that of a macrocyclic trimer with a new acyl group, an isodehydrovaloneoyl group, was established. This compound was also produced by callus tissues induced from O. laciniata leaves.
Callus tissue cultures induced from an axenic leaf of Eriobotrya japonica (Rosaceae) produced triterpenes in large amounts (ca. 50 mg/g dry wt). Nine triterpenes were characterized as ursolic acid, oleanolic acid, 2alpha-hydoxyursolic acid, maslinic acid, tormentic acid, 2alpha, 19alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid, hyptadienic acid and a mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid. The triterpene composition in the callus tissues was noticeably different from that in intact leaves. The contents of tormentic acid with antidiabetic action, and 2alpha, 19alpha-dihydroxy-3-oxo-urs-12-en-28-oic acid with anti-HIV activity, were much larger than those in the intact leaves. All of the triterpenes isolated from the callus tissues showed an inhibitory effect comparable to (-)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 2alpha, 19alpha-Dihydroxy-3-oxo-urs-12-en-28-oic acid was the most potent inhibitor among them and caused a significant delay of two-stage carcinogenesis on mouse skin.