Biomedical subjects

Harukuni Tokuda

Publications and source records attributed to Harukuni Tokuda.

At least 91 records · Page 5Linked to original sources

PubMed2003

Potential antitumor promoting diterpenoids from the stem bark of Thuja standishii.

Six diterpenes, including one new natural product, were isolated from a CHCl 3 extract of the stem bark of Thuja standishii. The new compound has been characterized as 15-oxolabda-8(17),13 Z-dien-19-oic acid. The known compounds were identified as ferruginol (2), sugiol (3), isocupressic acid (4), sandaracopimaric acid (5) and 15-oxolabda-8(17),13 E-dien-19-oic acid (6). Compounds 2-5 and the derivatives 4a and 4b were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Compounds 2, 3, 4 and 5 showed strong inhibitory effect on EBV-EA induction (100 % inhibition at 1000 mol ratio/TPA).

Antineoplastic Agents, Phytogenic↗

PubMed2003

Two new anti-tumor promoting serratane-type triterpenoids from the stem bark of Picea jezoensis var. jezoensis.

Two new serratane-type triterpenoids, 1 and 2, were isolated from the stem bark of Picea jezoensis Carr. var. jezoensis (Pinaceae). Their structures were determined to be 3beta-methoxyserrat-13-en-21beta-ol (1) and 13beta, l4beta-epoxy-3beta-methoxyserratan-21beta-ol (2) on the basis of spectroscopic methods and partial syntheses. Compounds 1 and 2 and their acetates were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. IC50 value evaluation showed that compound 1 was more effective than others. In addition, compounds 1 and 2 were examined for anti-tumor promoting activities in a two-stage carcinogenesis assay of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compounds 1 and 2 exhibited significant anti-tumor promoting effects on mouse skin carcinogenesis.

Animals↗

PubMed2003

Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice.

Dietary antioxidants may attenuate oxidative damage from strenuous exercise in various tissues. Beneficial effects of the antioxidant astaxanthin have been demonstrated in vitro, but not yet in vivo. We investigated the effect of dietary supplementation with astaxanthin on oxidative damage induced by strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old) were divided into groups: rested control, intense exercise, and exercise with astaxanthin supplementation. After 3 weeks of exercise acclimation, both exercise groups ran on a treadmill at 28 m/min until exhaustion. Exercise-increased 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the astaxanthin group. Increases in plasma creatine kinase activity, and in myeloperoxidase activity in gastrocnemius and heart, also were lessened by astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the 3 week supplementation. Astaxanthin can attenuate exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Ichthyotoxic and anticarcinogenic effects of triterpenoids from Sandoricum koetjape bark.

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.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Anti-tumor promoting effect of glycosides from Prunus persica seeds.

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.

Animals↗

PubMed2003

Inhibitory effects of 3-O-acyl-(+)-catechins on Epstein-Barr virus activation.

In the course of an exploratory investigation of antitumor-promoting catechins, 3-O-acyl-(+)-catechins of varying carbon lengths from C(4) to C(18) were assessed for inhibitory effects on the activation of the Epstein-Barr virus early antigen. Like 3-O-acyl-(-)-epigallocatechins, the (+)-catechin derivatives showed promising effects with the C-3 acyl chain of C(8)-C(11) carbon atoms.

Antigens, Viral↗

PubMed2003

Three new quassinoids, ailantinol E, F, and G, from Ailanthus altissima.

Three new quassinoids, ailantinol E (1), ailantinol F (2), and ailantinol G (3), and related compounds were isolated from Ailanthus altissima grown in Taiwan. Their structures were elucidated from spectral evidence. Each new quassinoid was evaluated for its antitumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The new quassinoids were found to show potent activity without showing any cytotoxicity. The screening for inhibitors against nitric oxide donor action was also conducted using the new quassinoids and some standard samples.

Ailanthus↗

PubMed2002

Inhibitory effect of stabilized analogues of glycoglycerolipids on Epstein-Barr virus activation and mouse skin tumor promotion.

Nine new synthetic compounds, structurally related to the most active glycoglycerolipid analogues carrying a hexanoyl chain, were tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus (EBV) activation. All these compounds, in which the ester function is replaced by different metabolically more stable groups, were almost as active as their ester reference compounds in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Two of these, devoid of any functionality on the lipophilic chain, when tested in an in vivo two-stage carcinogenesis test, exhibited marked inhibitory effects on mouse skin tumor promotion.

Animals↗

PubMed2002

Cancer chemopreventive effect of quassinoid derivatives. Introduction of side chain to shinjulactone C for enhancement of inhibitory effect on Epstein-Barr virus activation.

A series of shinjulactone C (1) derivatives (2-8) were synthesized and evaluated for their anti-tumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The succinate and 3',3'-dimethylsuccinate derivatives of 1 exhibited higher inhibitory effects than 1. From the point of view of structure-activity relationships, the succinate derivatives (2, 4) demonstrated better potency than the glutarate derivatives (3, 5-8). As substituted moieties of 3'-position became bulky, the inhibitory effects of the glutarate derivatives (7, 8) significantly decreased.

Antigens, Viral↗

PubMed2002

Inhibitory effects of cucurbitane glycosides and other triterpenoids from the fruit of Momordica grosvenori on epstein-barr virus early antigen induced by tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

Two new triterpene benzoates, 5-dehydrokarounidiol dibenzoate (1) and karounidiol dibenzoate (2), and two new triterpene glycosides, 5alpha,6alpha-epoxymogroside IE(1) (8) and 11-oxomogroside A(1) (9), along with 15 known triterpenoids (one triterpene benzoate, 3; three triterpene mono-ols, 4-6; one triterpene aglycon, 7; and 10 triterpene glycosides, 10-19), were isolated from the ethanol extract of the fruit of Momordica grosvenori. The structures of 1, 2, 8, and 9 were determined on the basis of spectroscopic and chemical methods. Among the known triterpene glycosides, mogroside I E(1) (12) was a new naturally occurring compound. Eighteen triterpenoids (2-19) and 11-oxomogrol (20), a hydrolysis product of 9, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (70-100% inhibition at 1 x 10(3) mol ratio/TPA).

Antigens, Viral↗

PubMed2002

Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis.

In continuation of our works of natural and synthetic products as cancer chemopreventive agents, we have examined emodin and cassiamin B, which were isolated from Cassia siamea. These compounds exhibited the remarkable anti-tumor promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter by both topical application. Furthermore, emodin exhibited potent inhibitory activity on two-stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide as an initiator and TPA as a promoter.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Antitumor activity of compounds isolated from leaves of Eriobotrya japonica.

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.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

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.

Antigens, Viral↗

PubMed2002

Cancer chemopreventive activity of Achyranthes aspera leaves on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

Achyranthes aspera leaves have been assessed for chemopreventive activity. The MeOH extract, alkaloid, non-alkaloid and saponin fractions exhibited significant inhibitory effects (concentration 100 microg) on the Epstein-Barr virus early antigen activation induced by the tumor promotor 12-O-tetradecanoylphorbol-13-acetate in Raji cells. In this in vitro assay the non-alkaloid fraction containing mainly non-polar compounds showed the most significant inhibitory activity (96.9%; 60% viability). In the in vivo two-stage mouse skin carcinogenesis test the total methanolic extract possessed a pronounced anticarcinogenic effect (76%). The present study suggests that A. aspera leaf extract and the non-alkaloid fraction are valuable antitumor promotors in carcinogenesis.

Achyranthes↗

PubMed2002

Constituents of Compositae plants III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers.

Fifteen pentacyclic triterpene diols and triols, consisting of: six taraxastanes, faradiol (1), heliantriol B0 (2), heliantriol C (3), 22alpha-methoxyfaradiol (4), arnidiol (5), and faradiol alpha-epoxide (6); five oleananes, maniladiol (7), erythrodiol (8), longispinogenin (9), coflodiol (10), and heliantriol A(1) (11); two ursanes, brein (12) and uvaol (13); and two lupanes, calenduladiol (14) and heliantriol B2 (15), isolated from the non-saponifiable lipid fraction of the edible flower extract of chrysanthemum (Chrysanthemum morifolium) were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, in Raji cells as a primary screening test for anti-tumor-promoters. All of the compounds tested showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of glycyrrhetic acid, a known natural anti-tumor-promoter. Evaluation of the cytotoxic activity of six compounds, 1-3 and 5-7, against human cancer cell lines revealed that compound 5 possesses a wide range of cytotoxicity, with GI50 values (concentration that yields 50% growth) of mostly less than 6 microM.

Anticarcinogenic Agents↗

PubMed2002

Cancer chemopreventive activity of flavanones on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of ten flavanones isolated from plants belonging to Rutaceae and Leguminosae by examining their possible inhibitory effects on Epstein-Barr virus (EBV) early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the flavanones tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Amorilin (3), which has three prenyl (3-methyl-2-butenyl) side-chains in the molecule, showed the most potent activity. Furthermore, lupinifolin (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These results indicate that some of these prenylated flavanones might be valuable as potential cancer chemopreventive agents (anti-tumor promoters).

Animals↗

PubMed2002

Inhibitory effect of herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein-Barr virus early antigen activation.

For the past several years we have been evaluating natural products as potential cancer chemopreventive agents in a short term in vitro assay involving Epstein--Barr virus early antigen (EBV-EA) activation in Raji cells promoted by phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Because of the current interest in the use of herbal remedies, we considered examining them for their cancer chemopreventive activities, using their extracts with a view to uncovering such benefits (if any) these remedies might possess. Thirty-six extracts of 32 herbs belonging to 27 families in use as herbal remedies including those of gingko, black cohosh, echinacea, kava-kava, saw palmetto, turmeric, angelica, wild yam, cat's claw, passion flower, muira puama, feverfew, blueberry, chasteberry, licorice, nettle, golden seal, pygeum, ginger, valerian and hops were prepared and evaluated. Turmeric at a concentration of 10 microg x ml (-1)exhibited the most potent anti-EBV-EA activity, which is ten times more than passionflower, that is next in the order of activity. At the concentration level of 100 microg ml (-1), several of the herbal remedies tested inhibited the EBV-EA in Raji cells exposed to the tumor promoter TPA (32 pM) by more than 90%. We also report for the first time the activities of 16 new medicinal plants as potential cancer chemopreventive agents. Since inhibitors of EBV-EA promoted by TPA in vitro have been shown to be effective anti-tumor promoting agents in laboratory animal models, our results indicate new and potential applications of these herbal remedies as cancer chemopreventive agents since they are already in clinical use in the human population.

Antigens, Viral↗

PubMed2002

Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.

9,10-Dimethyl-1,2-benzanthracene↗