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 26

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
Kounosuke Oisaki
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.10, pp.907-919, 2018-10-01 (Released:2018-10-01)
参考文献数
40

To conduct organic synthesis in the field of pharmaceutical science, methodologies that can easily and quickly supply compounds with high drug-likeness are highly desirable. Based on the original catalyst design concept “Radical-Conjugated Redox Catalysis (RCRC)” established during my research, various C(sp3)–H functionalizations and protein modifications have been developed, taking advantage of the high reactivity and chemoselectivity of the single-electron transfer process. This review focuses on the eight-year research efforts by my collaborators and me, from conception to results.
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
Yağız Anıl Çiçek David C. Luther Jessica A. Kretzmann Vincent M. Rotello
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.42, no.3, pp.304-311, 2019-03-01 (Released:2019-03-01)
参考文献数
83

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has revolutionized therapeutic gene editing by providing researchers with a new method to study and cure diseases previously considered untreatable. While the full range and power of CRISPR technology for therapeutics is being elucidated through in vitro studies, translation to in vivo studies is slow. To date there is no totally effective delivery strategy to carry CRISPR components to the target site in vivo. The complexity of in vivo delivery is furthered by the number of potential delivery methods, the different forms in which CRISPR can be delivered as a therapeutic, and the disease target and tissue type in question. There are major challenges and limitations to delivery strategies, and it is imperative that future directions are guided by well-conducted studies that consider the full effect these variables have on the eventual outcome. In this review we will discuss the advances of the latest in vivo CRISPR/Cas9 delivery strategies and highlight the challenges yet to be overcome.
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
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 34

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
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 26

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
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 27

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
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
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
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
150 170

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
Yuko Yamakage Hitomi Tsuiji Takao Kohno Himari Ogino Takashi Saito Takaomi C. Saido Mitsuharu Hattori
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.42, no.3, pp.354-356, 2019-03-01 (Released:2019-03-01)
参考文献数
16

Reelin is a secreted protein that antagonizes the deposition and toxicity of amyloid β peptide (Aβ). Therefore, augmentation of Reelin activity may ameliorate Alzheimer’s disease (AD). We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS-3) cleaves and inactivates Reelin in the mouse brain. In the present study, we investigated the effect of reducing ADAMTS-3 on deposition of Aβ by crossbreeding drug-inducible ADAMTS-3 conditional knock-out (cKO) mice with “next-generation” AD model mice. We found that reducing ADAMTS-3 inhibited deposition of Aβ significantly in AppNL-F mice, which produce human wild-type Aβ. On the other hand, reducing ADAMTS-3 had no effect in AppNL-G-F mice, which produce the Arctic mutant Aβ (E22G) that forms protofibrils more efficiently than does wild-type Aβ. Thus, the findings suggest that the administration of an inhibitor against ADAMTS-3 will prevent the progression of AD pathology caused by deposition of wild-type Aβ.
著者
Shiho Nagata Tetsuro Marunouchi Kouichi Tanonaka
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b18-00785, (Released:2019-01-10)
参考文献数
38

Protein quality control (PQC) in the heart plays an important role to maintain cellular protein homeostasis. Impairment of PQC may cause the development of heart failure. It is well known that histone deacetylase 6 (HDAC6) is an essential enzyme for regulating the cellular PQC response. In this study, we aimed at examining the association between HDAC6 and the chaperone system and the effects of HDAC6 inhibition in the development of heart failure following myocardial infarction (MI). MI was induced by coronary artery ligation. Coronary artery-ligated and sham-operated rats were divided into groups that were orally administered suberoylanilide hydroxamic acid (SAHA) or vehicle from the 2nd to 8th week after the operation. The cardiac function and protein expression levels in the viable left ventricle were analyzed by echocardiography, western blotting, and immunohistochemistry at the 2nd and 8th weeks after the operation. The deacetylase activity of HDAC6 was markedly elevated during the development of heart failure after MI. In the failing heart, a decrease in heat-shock protein (HSP) contents and an accumulation of ubiquitinated proteins were observed, indicating PQC dysfunction. Inhibition of HDAC6 activity by SAHA treatment enhanced the translocation of heat-shock transcription factor 1 to the nucleus and induced the expression of HSP, resulting in maintenance of cellular protein homeostasis. The cardiac pump function after MI was also improved by SAHA administration. Our findings suggest that inhibition of HDAC6 activity is a novel approach for the treatment of heart failure following MI.
著者
Keiko MORITO Toshiharu HIROSE Junei KINJO Tomoki HIRAKAWA Masafumi OKAWA Toshihiro NOHARA Sumito OGAWA Satoshi INOUE Masami MURAMATSU Yukito MASAMUNE
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.24, no.4, pp.351-356, 2001 (Released:2002-04-26)
参考文献数
37
被引用文献数
309 335

The human estrogen receptor (hER) exists as two subtypes, hER α and hER β, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER α or hER β protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER β than to hER α. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 β-estradiol. Equol induces transcription most strongly with hER α and hER β. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half the activity of 17 β-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.
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 15

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
3

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.