著者
Tomoharu Kuboyama Chihiro Tohda Katsuko Komatsu
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.37, no.6, pp.892-897, 2014-06-01 (Released:2014-06-01)
参考文献数
60
被引用文献数
16 25

Neurodegenerative diseases commonly induce irreversible destruction of central nervous system (CNS) neuronal networks, resulting in permanent functional impairments. Effective medications against neurodegenerative diseases are currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. In this review, we summarize various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer’s disease and spinal cord injury.
著者
Khem Raj Joshi Hari Prasad Devkota Takashi Watanabe Shoji Yahara
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.62, no.2, pp.191-195, 2014-02-01 (Released:2014-02-01)
参考文献数
24
被引用文献数
3 4

Three new glycosides: thotneoside A (quercetin 3-O-(6″-O-phenylacetyl)-β-D-galactopyranoside) (1), thotneoside B (quercetin 3-O-(6″-O-phenylacetyl)-β-D-glucopyranoside) (2) and thotneoside C (3-methyl-2-butenoic acid 1-O-β-D-glucopyranoside) (3), together with nine known compounds; quercetin (4), quercetin 3-O-β-D-galactopyranoside (5), quercetin 3-O-(6″-O-galloyl)-β-D-galactopyranoside (6), quercetin 3-O-β-D-galacturonopyranoside (7), quercetin 3-O-β-D-glucuronopyranoside (8), quercetin 3-O-α-L-rhamnopyranoside (9), rutin (10), quercetin 3-O-α-L-arabinopyranoside (11) and 2,4,6-trihydroxyacetophenone 2-O-β-D-glucopyranoside (12) have been isolated from the shade dried leaves of Aconogonon molle, commonly known as “Thotne″ in Nepal. The structures were elucidated on the basis of chemical and spectroscopic methods. All of these compounds were isolated for the first time from A. molle and their in vitro antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Quercetin (4) and its glycosides (1–2, 5–11) showed potent free radical scavenging activity.
著者
Daisuke Furushima Hiroshi Yamada Michiko Kido Yuko Ohno
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.3, pp.409-418, 2018-03-01 (Released:2018-03-01)
参考文献数
40

Improvement in patient waiting time in dispensing pharmacies is an important element for patient and pharmacists. The One-Dose Package (ODP) of medicines was implemented in Japan to support medicine adherence among elderly patients; however, it also contributed to increase in patient waiting times. Given the projected increase in ODP patients in the near future owing to rapid population aging, development of improved strategies is a key imperative. We conducted a cross-sectional survey at a single dispensing pharmacy to clarify the impact of ODP on patient waiting time. Further, we propose an improvement strategy developed with use of a discrete event simulation (DES) model. A total of 673 patients received pharmacy services during the study period. A two-fold difference in mean waiting time was observed between ODP and non-ODP patients (22.6 and 11.2 min, respectively). The DES model was constructed with input parameters estimated from observed data. Introduction of fully automated ODP (A-ODP) system was projected to reduce the waiting time for ODP patient by 0.5 times (from 23.1 to 11.5 min). Furthermore, assuming that 40% of non-ODP patients would transfer to ODP, the waiting time was predicted to increase to 56.8 min; however, introduction of the A-ODP system decreased the waiting time to 20.4 min. Our findings indicate that ODP is one of the elements that increases the waiting time and that it might become longer in the future. Introduction of the A-ODP system may be an effective strategy to improve waiting time.
著者
Hiroaki Takemoto Jun Takahashi Sumiko Hyuga Hiroshi Odaguchi Nahoko Uchiyama Takuro Maruyama Tadatoshi Yamashita Masashi Hyuga Naohiro Oshima Yoshiaki Amakura Takashi Hakamatsuka Yukihiro Goda Toshihiko Hanawa Yoshinori Kobayashi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.2, pp.247-253, 2018-02-01 (Released:2018-02-01)
参考文献数
33
被引用文献数
2

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline β1 receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.
著者
Lucia Renee Ruhaak Jenny Felth Pernilla Christina Karlsson Joseph James Rafter Robert Verpoorte Lars Bohlin
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.34, no.5, pp.774-778, 2011-05-01 (Released:2011-05-01)
参考文献数
35
被引用文献数
23 26

Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors. Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process. They have also been shown to inhibit cancer cell proliferation. Anti-inflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the development of colon cancer, which makes this subject interesting to study further. In the present work, the six cannabinoids tetrahydrocannabinol (Δ9-THC), tetrahydrocannabinolic acid (Δ9-THC-A), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG) and cannabigerolic acid (CBGA), isolated from Cannabis sativa, were evaluated for their effects on prostaglandin production. For this purpose an in vitro enzyme based COX-1/COX-2 inhibition assay and a cell based prostaglandin production radioimmunoassay were used. Cannabinoids inhibited cyclooxygenase enzyme activity with IC50 values ranging from 1.7·10−3 to 2.0·10−4 M.
著者
Jun Shimokawa
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.66, no.2, pp.105-115, 2018-02-01 (Released:2018-02-01)
参考文献数
153
被引用文献数
1

The divergent total syntheses of three types of heteropolycyclic natural products, namely gelsedine-type alkaloids, amathaspiramide alkaloids, and erythrina alkaloids, are outlined. A strategy involving a late-stage pluripotent common synthetic intermediate prepared via original and innovative transformations was employed. A brief description of the philosophy and criteria for choosing the synthetic targets and common synthetic precursors, as well as details regarding the development of the overall synthetic schemes from a common intermediate are discussed.
著者
Adriana Meri Mestrimer Felipe Vinicius Pires Rincão Fabrício José Benati Rosa Elisa Carvalho Linhares Karen Janaina Galina Cleyton Eduardo Mendes de Toledo Gisely Cristiny Lopes João Carlos Palazzo de Mello Carlos Nozawa
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.29, no.6, pp.1092-1095, 2006 (Released:2006-06-01)
参考文献数
22
被引用文献数
22 29

Crude extract (CE) and aqueous (AqF) and ethyl acetate (EtOAcF) fractions of Guazuma ulmifolia LAM., Sterculiaceae and the corresponding AqF, EtOAcF of Stryphnodendron adstringens (MART.) COVILLE, Leguminosae were tested for their antiviral activity against poliovirus 1 (P-1) and bovine herpesvirus 1 (BHV-1) in HEp-2 cultured cells. The antiviral activity was monitored by plaque assay and immunofluorescence assay (IFA) under virucidal and therapeutic protocols. The therapeutic protocol demonstrated statistically significant positive results with both plants and for both virus strains. The highest percentages of viral inhibition were found for G. ulmifolia EtOAcF which inhibited BHV-1 and P-1 replication by 100% and 99%, respectively (p<0.05, Student's t-test). For S. adstringens, AqF was the most efficient, inhibiting BHV-1 and P-1 by 97% and 93%, respectively (p<0.05). In the virucidal protocol, G. ulmifolia CE inhibited the replication of BHV-1 and P-1 by 60% and 26%, respectively (p<0.05), while, for S. adstringens, inhibition of 62% (p<0.05) was demonstrated only with EtOAcF for P-1. IFA demonstrated that the greatest reduction in fluorescent cell number occurred with G. ulmifolia, under the therapeutic protocol for both virus strains. However, AqF and EtOAcF of S. adstringens were most efficient with the virucidal protocol for P-1. In conclusion, we demonstrated that G. ulmifolia and S. adstringens inhibited BHV-1 and P-1 replication, as well as, blocked the synthesis of viral antigens in infected cell cultures.
著者
Kiyoko Kaneko Yasuo Aoyagi Tomoko Fukuuchi Katsunori Inazawa Noriko Yamaoka
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.37, no.5, pp.709-721, 2014-05-01 (Released:2014-05-01)
参考文献数
42
被引用文献数
11 24

Purines are natural substances found in all of the body’s cells and in virtually all foods. In humans, purines are metabolized to uric acid, which serves as an antioxidant and helps to prevent damage caused by active oxygen species. A continuous supply of uric acid is important for protecting human blood vessels. However, frequent and high intake of purine-rich foods reportedly enhances serum uric acid levels, which results in gout and could be a risk factor for cardiovascular disease, kidney disease, and metabolic syndrome. In Japan, the daily intake of dietary purines is recommended to be less than 400 mg to prevent gout and hyperuricemia. We have established an HPLC method for purine analysis and determined purines in a total of 270 foodstuffs. A relatively small number of foods contained concentrated amounts of purines. For the most part, purine-rich foods are also energy-rich foods, and include animal meats, fish meats, organs such as the liver and fish milt, and yeast. When the ratio of the four purine bases (adenine, guanine, hypoxanthine, and xanthine) was compared, two groups of foods were identified: one that contained mainly adenine and guanine and one that contained mainly hypoxanthine. For patients with gout and hyperuricemia, the amount of total purines and the types of purines consumed, particularly hypoxanthine, are important considerations. In this context, the data from our analysis provide a purine content reference, and thereby clinicians and patients could utilize that reference in nutritional therapy for gout and hyperuricemia.
著者
Masashi Kitamura Masako Aragane Kou Nakamura Tatsushi Adachi Kazuhito Watanabe Yohei Sasaki
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.8, pp.1303-1306, 2018-08-01 (Released:2018-08-01)
参考文献数
15
被引用文献数
1

Cannabis sativa L. is cultivated worldwide for a variety of purposes, but its cultivation and possession are regulated by law in many countries, necessitating accurate detection methods. We previously reported a DNA-based C. sativa identification method using the loop-mediated isothermal amplification (LAMP) assay. Although the LAMP technique can be used for on-site detection, our previous protocol took about 90 min from sampling to detection. In this study, we report an on-site protocol that can be completed in 30 min for C. sativa identification based on a modified LAMP system. Under optimal conditions, the LAMP reaction started at approximately 10 min and was completed within 20 min at 63°C. It had high sensitivity (10 pg of purified DNA). Its specificity for C. sativa was confirmed by examining 20 strains of C. sativa and 50 other species samples. With a simple DNA extraction method, the entire procedure from DNA extraction to detection required only 30 min. Using the protocol, we were able to identify C. sativa from various plant parts, such as the leaf, stem, root, seed, and resin derived from C. sativa extracts. As the entire procedure was completed using a single portable device and the results could be evaluated by visual detection, the protocol could be used for on-site detection and is expected to contribute to the regulation of C. sativa.
著者
Yo Muraki Midori Yamasaki Hirohisa Takeuchi Kimio Tohyama Noriyasu Sano Takanori Matsuo
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
pp.c17-00811, (Released:2018-01-06)
参考文献数
36

Pulmonary hypertension (PH) is a life-threatening lung disease. Despite the availability of several approved drugs, the development of a new treatment method is needed because of poor prognosis. Tissue selective drug delivery systems can avoid the adverse effects of current therapy and enhance efficacy. We evaluated the possibility of delivering drugs to the lungs of a PH rat model using fluorescence dye-labeled nanosized liposomes. To evaluate the tissue distribution following systemic exposure, fluorescent dye-labeled, 40-180 nm liposomes with and without polyethylene glycol (PEG) were intravenously administered to a monocrotaline-induced PH (MCT) rat model and tissue fluorescence was measured. Fluorescent dye-containing liposomes were intratracheally administered to the MCT model to evaluate the distribution of the liposome-encapsulated compound following local administration to reduce systemic exposure. The lung vascular permeability, plasma concentration of surfactant protein (SP)-D, lung reactive oxygen species (ROS) production, and macrophage marker gene cluster of differentiation (CD68) expression were measured. PEG and 80-nm liposome accumulation in the lung was elevated in the MCT model compared to that in normal rats. The intratracheally administered liposomes were delivered selectively to the lungs of the MCT model. The lung vascular permeability, plasma SP-D concentration, and CD68 expression were significantly elevated in the lungs of the MCT model, and were all significantly and positively correlated to liposome lung accumulation. Liposomes can accumulate in the lungs of an MCT model by enhancing vascular permeability by the inflammatory response. Therefore, drug encapsulation in liposomes could be an effective method of drug delivery in patients with PH.
著者
Ken Takeda Ken-ichiro Suzuki Aki Ishihara Miyoko Kubo-Irie Rie Fujimoto Masako Tabata Shigeru Oshio Yoshimasa Nihei Tomomi Ihara Masao Sugamata
出版者
The Pharmaceutical Society of Japan
雑誌
Journal of Health Science (ISSN:13449702)
巻号頁・発行日
vol.55, no.1, pp.95-102, 2009 (Released:2009-02-01)
参考文献数
31
被引用文献数
150 167

Nanomaterials are being used increasingly for commercial purposes, yet little is known about the potential health hazards such materials may pose to consumers and workers. Here we show that nano-sized titanium dioxide (TiO2), which is used widely as a photo-catalyst and in consumer products, administered subcutaneously to pregnant mice is transferred to the offspring and affects the genital and cranial nerve systems of the male offspring. Nanoparticles identified as TiO2 by energy-dispersive X-ray spectroscopy were found in testis and brain of exposed 6-week-old male mice. In the offspring of TiO2-injected mice, various functional and pathologic disorders, such as reduced daily sperm production and numerous caspase-3 (a biomarker of apoptosis) positive cells in the olfactory bulb of the brain, were observed. Our findings suggest the need for great caution to handle the nanomaterials for workers and consumers.
著者
Masao Toyota Takuji Shimamura Hikari Ishii Matt Renner John Braggins Yoshinori Asakawa
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.50, no.10, pp.1390-1392, 2002 (Released:2002-10-01)
参考文献数
5
被引用文献数
26 32

The ether extract of the New Zealand liverwort Radula marginata afforded a new cannabinoid type bibenzyl compound named perrottetinenic acid, and two new bibenzyls, together with a known cannabinoid, perrottetinene. Their structures were established by two dimensional (2D) NMR spectral data. The structure of perrottetinenic acid was a similar to that of Δ1-tetrahydrocannabinol, a known hallucinogen. Cannabinoid type bibenzyls have been isolated from liverwort Radula perrottetii, though have not previously been reported from the liverwort R. marginata.
著者
Yasushi Hori Manami Fujisawa Kenji Shimada Akira Oda Shinichiro Katsuyama Keiji Wada
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.27, no.4, pp.486-491, 2004 (Released:2004-04-01)
参考文献数
17
被引用文献数
11 13

We have established a new method of HPLC analysis for the rapid separation from human serum and the quantification of 4-O-methylpyridoxine (MPN), which is contained in Ginkgo biloba seeds, and which, when consumed in large amounts, causes vomiting and convulsions. As a result of using IPCC-MS3 (GL Science, Tokyo, Japan), an ion-pair reagent, in the mobile phase, we succeeded in separating MPN in the deproteinized serum sample which was introduced directly onto the reverse-phase HPLC column. For the calibration curve of MPN standard solution, prepared with fluorescence detection at an excitation wavelength of 290 nm and an emission wavelength of 400 nm, a good linear relationship was obtained within the HPLC injection range of 10 ng—10 pg (in terms of the injected sample concentration, range: 1.0 μg/ml—1 ng/ml), allowing the detection of minute amounts, with the limit of detection (concentration of injected sample: 500 pg/ml) being 5 pg. In addition, when MPN solution was added to human reference serum to give a concentration of 0.002 μg/ml, the mean recovery rate was 92.5%, with RSD=7.09% (n=5). The time required for one analysis using this method is approximately 30 min, and thus it offers the advantages of greater speed and superior analytical sensitivity over the conventional methods, which require solid-phase extraction. We employed our new method to determine both the serum levels of MPN in 5 patients with Ginkgo biloba seed poisoning and the levels of free-form MPN in such seeds obtained in 8 regions of Japan.
著者
Yu Fukuoka El-Sayed Khafagy Takahiro Goto Noriyasu Kamei Kozo Takayama Nicholas A. Peppas Mariko Takeda-Morishita
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.5, pp.811-814, 2018-05-01 (Released:2018-05-01)
参考文献数
14
被引用文献数
1

In previous studies we showed that the complexation hydrogels based in poly(methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)] rapidly release insulin in the intestine owing to their pH-dependent complexation properties; they also exhibit a high insulin-loading efficiency, enzyme-inhibiting properties, and mucoadhesive characteristics. Cell-penetrating peptides (CPPs), such as oligoarginines [hexa-arginine (R6), comprising six arginine residues], have been employed as useful tools for the oral delivery of therapeutic macromolecules. The aim of our study was to investigate the combination strategy of using P(MAA-g-EG) hydrogels with R6-based CPPs to improve the intestinal absorption of insulin. A high efficiency of loading into crosslinked P(MAA-g-EG) hydrogels was observed for insulin (96.1±1.4%) and R6 (46.6±3.8%). In addition, immediate release of the loaded insulin and R6 from these hydrogels was observed at pH 7.4 (80% was released in approximately 30 min). Consequently, a strong hypoglycemic response was observed (approximately 18% reduction in blood glucose levels) accompanied by an improvement in insulin absorption after the co-administration of insulin-loaded particles (ILP) and R6-loaded particles (ALP) into closed rat ileal segments compared with that after ILP administration alone. These results indicate that the combination of P(MAA-g-EG) hydrogels with CPPs may be a promising strategy for the oral delivery of various insulin preparations as an alternative to conventional parenteral routes.
著者
Tomohito Tsukamoto Eiko Sakai Shunsuke Iizuka Marcos Taracena-Gándara Fuminori Sakurai Hiroyuki Mizuguchi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.41, no.7, pp.1089-1095, 2018-07-01 (Released:2018-07-01)
参考文献数
37

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 system is now widely used as a genome editing tool. CRISPR-associated endonuclease in Prevotella and Francisella 1 (Cpf1) is a recently discovered Cas endonuclease that is designable and highly specific with efficiencies comparable to those of Cas9. Here we generated the adenovirus (Ad) vector carrying an Acidaminococcus sp. Cpf1 (AsCpf1) expression cassette (Ad-AsCpf1) for the first time. Ad-AsCpf1 was applied to primary human hepatocytes prepared from humanized mice with chimeric liver in combination with the Ad vector expressing the guide RNA (gRNA) directed to the Adeno-associated virus integration site 1 (AAVS1) region. The mutation rates were estimated by T7 endonuclease I assay around 12% of insertion/deletion (indel). Furthermore, the transduced human hepatocytes were viable (ca. 60%) at two weeks post transduction. These observations suggest that the Ad vector-mediated delivery of the CRISPR/AsCpf1 system provides a useful tool for genome manipulation of human hepatocytes.
著者
Mitsuyoshi Okita Yuki Yayoshi Kousuke Ohara Akio Negishi Hayato Akimoto Naoko Inoue Sachihiko Numajiri Shigeru Ohshima Seiichi Honma Shinji Oshima Daisuke Kobayashi
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.40, no.10, pp.1730-1738, 2017-10-01 (Released:2017-10-01)
参考文献数
21

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.
著者
Tomoichiro Asano Midori Fujishiro Akifumi Kushiyama Yusuke Nakatsu Masayasu Yoneda Hideaki Kamata Hideyuki Sakoda
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.30, no.9, pp.1610-1616, 2007-09-01 (Released:2007-09-01)
参考文献数
44
被引用文献数
29 36

Inositol phospholipids phosphorylated on D3-position of their inositol rings (3-phosphoinositides) are known to play important roles in various cellular events. Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110α or p110β. Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. Accumulated PI(3,4,5)P3 activates several serine/threonine kinases containing a PH (pleckstrin homology) domain, including Akt, atypical PKCs, p70S6 kinase and GSK.In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus.
著者
Mahitab Elsayed Daisuke Kobayashi Toshio Kubota Naoya Matsunaga Ryusei Murata Yuko Yoshizawa Natsuki Watanabe Tohru Matsuura Yuya Tsurudome Takashi Ogino Shigehiro Ohdo Takao Shimazoe
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.39, no.8, pp.1238-1246, 2016-08-01 (Released:2016-08-01)
参考文献数
64
被引用文献数
2 7

Bisphosphonates and statins are known to have antitumor activities against different types of cancer cell lines. In the present study, we investigated the antiproliferative effects of the combination of zoledronic acid (ZOL), a bisphophosphonate, and fluvastatin (FLU), a statin, in vitro on two types of human pancreatic cancer cell lines, Mia PaCa-2 and Suit-2. The pancreatic cancer cell lines were treated with ZOL and FLU both individually and in combination to evaluate their antiproliferative effects using WST-8 cell proliferation assay. In this study, we demonstrated a potent synergistic antiproliferative effect of both drugs when used in combination in both cell lines. Moreover, we studied the molecular mechanism behind this synergistic effect, which was inhibited by the addition of the mevalonate pathway products, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Furthermore, we aimed to determine the effect of ZOL and FLU combination on RhoA and Ras guanosine 5′-triphosphate (GTP)-proteins. The combination induced a marked accumulation in RhoA and unprenylated Ras. GGPP and FPP reversed the increase in the amount of both proteins. These results indicated that the combination treatment impaired RhoA and Ras signaling pathway by the inhibition of geranylgeranylation and/or farnesylation. This study provides a potentially effective approach for the treatment of pancreatic cancer using a combination treatment of ZOL and FLU.
著者
Takuya Izawa Koji Nakayama Noritaka Uchida Kazuhiro Nojima
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
pp.c17-00938, (Released:2018-02-22)
参考文献数
30

Dehydroacetic acid (1) was found to induce photoisomerization, converting aldrin (3) and dieldrin (4) into photoaldrin (5) and photodieldrin (6), respectively, not only when irradiated with artificial light at wavelengths longer than 290 nm in air but also when exposed to sunlight in air. By contrast, sodium dehydroacetate (2) induced both photoisomerization, primarily converting 3 to 5 and photoepoxidation, partially forming 6. Thus, because 2 is usually used as a water-soluble antiseptic, photo-erethism might occur due to the isomerization and epoxidation properties of this compound. The difference between the photoreactivity of 1 and that of 2 might be attributed to the spin density of the odd electron on the carbon atom in the respective radicals that were formed after photo-excited 1 and 2 caused H-abstraction.
著者
Naofumi Seira Naoki Yanagisawa Akiko Suganami Takuya Honda Makiko Wasai John W. Regan Keijo Fukushima Naoto Yamaguchi Yutaka Tamura Takayoshi Arai Toshihiko Murayama Hiromichi Fujino
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.40, no.10, pp.1806-1812, 2017-10-01 (Released:2017-10-01)
参考文献数
31
被引用文献数
1

Increases in the expression of prostaglandin E2 (PGE2) are widely known to be involved in aberrant growth in the early stage of colon cancer development. We herein demonstrated that the novel indole compound MW-03 reduced PGE2-induced cAMP formation by catalization to an inactive metabolite by inducing 15-hydroxyprostaglandin dehydrogenase through the activation of peroxisome proliferator-activated receptor-γ. MW-03 also inhibited colon cancer cell growth by arresting the cell cycle at the S phase. Although the target of MW-03 for cell cycle inhibition has not yet been identified, these dual anti-cancer effects of MW-03 itself and/or its leading compound(s) on colon cancer cells may reduce colon cancer development and, thus, have potential as a novel treatment for the early stage of this disease.