Biomedical subjects

Jiro Takata

Publications and source records attributed to Jiro Takata.

10 recordsLinked to original sources

PubMed2006

Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin.

We previously demonstrated that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG) converts to gamma-Toc in the mouse skin and has a higher bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce photo-inflammation in mouse skin, and compared its effectiveness to that of alpha-Toc acetate (alpha-TA). Topical pre- or post-application of 5% gamma-TDMG significantly reduced the formation of edema and tempered the increase in cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E2 (PGE2) that were induced by a single dose of UV irradiation of 2 kJ/m2 (290-380 nm, maximum 312 nm). The pre-treatment of mouse skin with 10% alpha-TA had the same anti-inflammatory effect as did gamma-TDMG. In spite of same having the ability to reduce PGE2 levels, the effect of gamma-TDMG pre-treatment on the inhibition of COX-2 mRNA/protein expression was less than that seen with 10% alpha-TA. In contrast, the increase in COX-2 activity seen after UV exposure was reduced more by gamma-TDMG than by alpha-TA, suggesting that the reduction in PGE2 levels might have been due to the direct inhibition of COX-2 activity by gamma-TDMG-derived gamma-Toc. Both Toc derivatives strongly suppressed inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production, both of which play important roles in UV-induced inflammation. Both derivatives also significantly reduced lipid peroxidation in response to UV exposure, though gamma-TDMG's ability in this regard was less than that seen with alpha-TA, which correlated with their abilities to suppress COX-2 expression. Thus, the gamma-TDMG-derived gamma-Toc acts as an antioxidant, suppresses iNOS expression and directly inhibits COX-2 activity, all of which likely play a role in mediating its suppressive effects on photo-inflammation. Our data further suggest that the topical application of gamma-TDMG, a novel hydrophilic gamma-Toc derivative, may be efficacious in preventing and reducing UV-induced inflammation in humans.

Administration, Topical↗

PubMed2006

Topical application of gamma-tocopherol derivative prevents UV-induced skin pigmentation.

We previously reported that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopheryl-N,N-dimethylglycinate hydrochloride (gamma-TDMG) gets converted to the antioxidant gamma-Toc in skin. We also found that this derivative displayed greater bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce UV-induced skin pigmentation in brownish guinea pigs. gamma-TDMG (0.1 or 0.5%) was topically applied to the skin before and after it was exposed to UVB plus UVA (3 times/week for 1 week), and then 10 times/week for 4 weeks thereafter. Treatment with 0.5% gamma-TDMG resulted in significant skin lightening (70% of the pigmentation of irradiated controls). We also found that melanin synthesis was dose-dependently inhibited by gamma-TDMG in murine B16 melanoma cells. When gamma-TDMG or kojic acid (250 microM) were added to homogenates of B16 melanoma cells, their tyrosinase activity was significantly inhibited by approximately 40% and 75%, respectively. Mushroom tyrosinase activity was significantly inhibited by 200 microM gamma-Toc and kojic acid, but not gamma-TDMG. When B16 cells were incubated with 250 microM gamma-TDMG for 24 or 48 h, their intracellular gamma-Toc concentrations rose over 100 fold to 10.5 and 11.2 nmol/10(6) cells, respectively, suggesting that gamma-TDMG was rapidly converted to gamma-Toc in these cells and that their reduced melanin synthesis may have been due to the activity of gamma-Toc. Our data further suggest that the topical application of gamma-TDMG may be efficacious in preventing photo-induced skin pigmentation in humans.

Administration, Topical↗

PubMed2006

Antiproliferative constituents from umbelliferae plants. IX. New triterpenoid glycosides from the fruits of Bupleurum rotundifolium.

The MeOH extract of the fruits of Bupleurum rotundifolium showed inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. Bioactivity-guided fractionation of the MeOH extract led to the isolation of four new triglycosides of 13beta,28-epoxy oleanane-type triterpenes, named rotundiosides O, Q, S and T; 12 new glycosides of oleanane-type triterpenes, named rotundiosides J-N, P, R, U-Y, and others; echinocystic acid 3-O-sulfate; and three known oleanane-type triterpene glycosides, rotundiosides A, F and G. The structures of the new isolates were determined based on chemical and spectroscopic evidence. The GI(50) of isolates against MK-1, HeLa and B16F10 cell lines are reported.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Technetium labeling of dextran incorporating cysteamine as a ligand.

INTRODUCTION: Technetium-99m-labeled dextran is a useful imaging agent for procedures such as angiocardiography and lymphoscintigraphy. To improve the availability of 99mTc-labeled dextran, we designed a cysteamine ligand system for dextran labeling. METHODS: Cysteamine derivatized dextran was synthesized as follows. Dextran was oxidized with sodium periodate, coupled with cysteamine and reduced with sodium borohydride to provide the desired amine ligand. The cysteamine-dextran conjugate was then labeled with reduced 99mTc. Whole-body scintigraphy and biodistribution were examined following injection of the 99mTc-labeled cysteamine-conjugated dextran (99mTc-cysteamine-dextran) in ICR mice. Lymphoscintigraphy was performed after intradermal injection of 99mTc-cysteamine-dextran in SD rats. RESULTS: The cysteamine-derived dextran was easily labeled with reduced 99mTc in greater than 96% yield. 99mTc-cysteamine-dextran has a higher chelation stability against diethylenetriamine pentaacetic acid (DTPA) than the 99mTc-dextran. Axillary lymph nodes were clearly visible after intradermal injection of 99mTc-cysteamine-dextran in rats. CONCLUSION: These results suggest that 99mTc-cysteamine-dextran is available for lymphoscintigraphy. This methodology could expand the usage of 99mTc-labeled dextran, particularly for diagnostic purposes.

Animals↗

PubMed2005

Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from Centella asiatica.

The antiproliferative constituents in the MeOH extract from the aerial parts of Centella asiatica were investigated. Activity-guided fractionation of MeOH extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic acid, 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, asiatic acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the isolated compounds against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.

Apiaceae↗

PubMed2003

Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral infarction in mice.

Alpha-tocopherol and its derivatives have been shown to be effective in reducing cerebral ischemia-induced brain damage. However, the effects of other vitamin E isoforms have not been characterized. In the present study, we investigated the effects of six different isoforms of vitamin E on the ischemic brain damage in the mice middle cerebral artery (MCA) occlusion model. All vitamin E isoforms were injected i.v., twice, immediately before and 3 h after the occlusion. Alpha-tocopherol (2 mM), alpha-tocotrienol (0.2 and 2 mM) and gamma-tocopherol (0.2 and 2 mM) significantly decreased the size of the cerebral infarcts 1 day after the MCA occlusion, while gamma-tocotrienol, delta-tocopherol and delta-tocotrienol showed no effect on the cerebral infarcts. These results suggest that alpha-tocotrienol and gamma-tocopherol are potent and effective agents for preventing cerebral infarction induced by MCA occlusion.

Animals↗

PubMed2003

The behavior of dihydropyrazine with DNA strand-breakage activity in vivo.

The effects on the viability of cell lines treated with 2,3-dihydro-5,6-dimethylpyrazine and its derivatives, which revealed DNA strand-breakage activity by the generation of radicals in vitro, were recognized from certain morphological changes and the detection of apoptosis-related proteins: cleaved PARP and SAPK/JNK. These results would suggest that sugar-derived dihydropyrazines induce changes in the cells of certain organs and cause various internal injuries in vivo. The biodistribution of 14C-labelled 2,3-dihydro-5,6-dimethylpyrazine was studied in mouse and the autoradiograms showed highly contrasting results. Radioactivity was high in the brain, spinal cord, salivary gland, and thymus and low in the heart, stomach, and blood. The result was supported by the activity (% dose per organ).

Animals↗

PubMed2002

Delivery systems for antioxidant nutrients.

The novel role of oxidants and antioxidants as part of cell signaling cascades has opened new areas of research in several disease states and their therapeutic strategies. For successful therapeutic manipulation of reactive oxygen species (ROS)-mediated cellular signaling pathways, it would necessitate control of the critical balance of oxidants/antioxidants in the target site by the antioxidant. Another way of controlling the critical balance is to avoid excessive generation of ROS from nutrients and/or drugs. From the viewpoint of controlling the balance between the oxidant and antioxidant status, this review focuses on the prodrug approach for delivery systems of vitamin E, a major antioxidant nutrient in the membrane, and on the reductive activation-independent delivery system of vitamin K hydroquinone by a prodrug approach, which can avoid excessive generation of ROS synchronized with the activation process of vitamin K.

Animals↗

PubMed2002

Novel d-gamma-tocopherol derivative as a prodrug for d-gamma-tocopherol and a two-step prodrug for S-gamma-CEHC.

d-gamma-Tocopherol (gamma-Toc) and its major metabolite, 2, 7, 8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman (S-gamma-CEHC), are currently receiving attention concerning their unique pharmacological activities. In order to achieve the efficient delivery of gamma-Toc and S-gamma-CEHC in vivo, we synthesized d-gamma-tocopheryl N,N-dimethylglycinate hydrochloride (gamma-TDMG) as a water-soluble prodrug of gamma-Toc and a two-step prodrug of S-gamma-CEHC. gamma-TDMG is a solid (mp 161-163 degrees C) and is quite soluble in water over 50 mM. The hydrolysis of gamma-TDMG was effectively catalyzed by esterases in rat and human liver microsomes. The disposition of gamma-TDMG after iv administration in rats was compared with that of gamma-Toc solubilized with the surfactant, polyoxyethylene hydrogenated castor oil. The plasma and liver levels of gamma-Toc rapidly increased after the iv administration of the gamma-TDMG. The liver availability of gamma-Toc after the administration of gamma-TDMG was two times higher than that of the gamma-Toc administration. The relative systemic availability of S-gamma-CEHC after the gamma-TDMG administration was an equivalent value (102%), and the mean residence time of S-gamma-CEHC was eight times longer than the racemic gamma-CEHC administration. Based on these results, gamma-TDMG was identified as the most promising water-soluble prodrug of gamma-Toc and the two-step prodrug of S-gamma-CEHC.

Animals↗

PubMedDate not supplied

Topical application of a novel, water-soluble gamma-tocopherol derivative prevents UV-induced skin damage in mice.

We investigated whether the topical application of a novel, water-soluble gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG), could protect against UV-induced skin damage in hairless mice. Topical pre- or post-application of a 5% (93 mM) gamma-TDMG solution in water/propylene glycol/ethanol (2:1:2) significantly prevented sunburn cell formation, lipid peroxidation and edema/inflammation that were induced by exposure to a single dose of UV irradiation of 5 kJ/m2 (290-380 nm, maximum 312 nm). This effect was greater than that seen with two alpha-Toc derivatives, alpha-tocopherol acetate (alpha-TA) and alpha-tocopherol-N,N-dimethylglycinate (alpha-TDMG). When a 5% solution of gamma-TDMG was applied to mouse skin for 1 h, cutaneous gamma-Toc increased by 25-fold after 24 h; levels of cutaneous alpha-Toc increased by only two- and eight-fold in alpha-TDMG and alpha-TA treated skins, respectively. These findings indicated that gamma-TDMG immediately converted to gamma-Toc in the skin and suggest that ability of gamma-TDMG to protect the skin from the damaging effects of irradiation was due to its conversion to gamma-Toc. When a 5% solution of gamma-Toc was applied to mouse skin for 1 h, cutaneous gamma-Toc rapidly increased by 25-fold, but fell to baseline levels by 24 h. In contrast, the concentration of gamma-Toc in skin that was treated with gamma-TDMG similarly increased, but these high levels were maintained after 24 h. These results suggest that gamma-TDMG may be a more effective source of gamma-Toc in skin. Thus, the topical application of gamma-TDMG may be efficacious for the prevention of UV-B-induced skin damage.

Administration, Topical↗