著者

Shinji Oshima Kazuhiko Senoo Akio Negishi Hayato Akimoto Kousuke Ohara Naoko Inoue Shigeru Ohshima Nobuaki Kutsuma Kazuhiko Juni 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.39, no.3, pp.313-322, 2016-03-01 (Released:2016-03-01)

参考文献数

20

被引用文献数

2 6

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Article 25-2 of the Japanese Pharmacists’ Act was revised in June 2014, establishing the position of pharmacists as “advisors on the use of pharmaceuticals.” Prior to the Act’s revision, we investigated the perceptions of patients and pharmacists about pharmacists’ roles using a social science methodology. We also examined current opinions and necessary factors for the future growth and development of pharmacists. This questionnaire survey was conducted using an internet method. Patients and pharmacists answered 12 questions. Responses from 529 patients and 338 pharmacists were analyzed. For all items, pharmacists’ awareness of their roles exceeded patients’ awareness of the roles. In this study, the difference between pharmacist and patient awareness was larger than in similar research conducted in the United States. The greatest difference was observed in three items: “Understanding the effects of the drugs the patients are taking” (rate of high ratings: pharmacists 80.2%, patients 37.8%), “Understanding the health changes caused by the drugs dispensed to the patients” (pharmacists 80.2%, patients 28.4%), and “Consciously protecting patients from the adverse effects of drugs” (pharmacists 82.8%, patients 42.2%), indicating role discrepancy. Partition analysis indicated the three factors for a pharmacist to be regarded as a drug therapy or medication specialist: “The patient regards the pharmacist as his/her family or regular pharmacist,” “The pharmacist is making it easy for a patient to talk with him/her” and “The pharmacist is aware of a patient’s use of products other than prescribed drugs, such as over the counter (OTC) medications or health foods and nutritional supplements.” Future efforts are necessary to resolve role discrepancy and implement ongoing monitoring.

著者

Insaf Bahrini Rikinari Hanayama

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.6, pp.977-981, 2019-06-01 (Released:2019-06-01)

参考文献数

26

被引用文献数

3

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Hepatitis C virus (HCV) infection leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in 50–80% of the cases. Interferons (IFNs) and the nucleoside analog ribavirin form the basis of the treatment of this infection but are not considered sufficiently effective and cause several side effects. In this study, we developed a novel viral-specific drug delivery method. Enveloped viruses, including HCV, expose an anionic phospholipid, phosphatidylserine (PS), on their surface to mediate their binding and entry into cells for infection. To target such exposed PS on HCV, we developed a chimeric recombinant protein containing human IFN and mouse lactadherin (also known as milk fat globule epidermal growth factor 8), which binds with high affinity to PS. The IFN–lactadherin fusion protein showed a high binding affinity toward PS and HCV and consequently blocked viral replication in the infected cells more efficiently than conventional IFN. Overall, these data suggest that conjugation with lactadherin facilitates the delivery of any protein drug to PS-exposing enveloped viruses.

著者

坂田 眞砂代 河合 透 大隈 邦夫 伊原 博隆 平山 忠一

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.16, no.11, pp.1065-1068, 1993-11-15 (Released:2008-04-10)

参考文献数

23

被引用文献数

11 12

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We describe a method for the removal of endotoxins from various crude antigen solutions originating from gram-negative bacteria using aminated poly(γ-methyl L-glutamate) (PMLG) spherical particles. The aminated PMLG adsorbents showed high affinity for various purified endotoxins at an ionic strength of μ=0.1. The endotoxin-adsorbing capacity of the adsorbent increased with increase in the amino-group content of the adsorbent. The adsorbent (3.2 meq/g amino-group content) showed the highest affinity for endotoxin at ionic strengths ranging from μ=0.025-0.8. The adsorption of Bordetella pertussis antigen to the adsorbent decreased with increasing amino-group content of the adsorbent at an ionic strength of μ=0.2. The adsorption of B. bronchiseptica protein to the adsorbent increased with increasing amino-group content of the adsorbent, but decreased with increasing ionic strength. The adsorbent (3.2 meq/g of amino-group content) selectively reduced endotoxin in crude antigen solutions originating from gram-negative bacteria, B. pertussis, B. bronchiseptica and Pasteurella multocida, even at a high ionic strength (μ=0.2-0.4) without affecting the recovery of the protective antigens.

著者

Gul Halise Inci Gul Mustafa Vespalainen Jouko ERCIYAS Ercin HANNINEN Osmo

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.5, pp.631-637, 2003-05-01

参考文献数

38

被引用文献数

2 23

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Acetophenone derived mono-Mannich bases (Ig1&mdash;Ig4), 1-aryl-3-amino-1-propanone hydrochlorides, which are known to have cytotoxicity in Jurkat cells, were synthesized. Then, they were converted to corresponding azine derivatives (D1&mdash;D4), <i>N</i>, <i>N</i>&prime;-bis(3-amino-1-aryl-propylidene)hydrazine dihydrochlorides, which are bifunctional agents. The aryl part was replaced by phenyl in Ig1, Ig2, Ig3, D1, D2, and D3, and by <i>p</i>-hydroxyphenyl in Ig4 and D4. The amine part was replaced by dimethylamine in Ig1, D1, Ig4 and D4, by piperidine in Ig2 and D2, and by morpholine in Ig3 and D3. The aim of this study was to investigate whether the modification in chemical structure, converting the mono-Mannich base to a corresponding azine derivative, improves the cytotoxicity. In addition, the effect of the representative compound, D3, <i>N</i>, <i>N</i>&prime;-bis(3-morpholine-4-yl-1-phenylpropylidene)hydrazine dihydrochloride, on cellular glutathione level after 1 h exposure in phosphate buffer at 37 &deg;C was also determined to provide information on a possible mechanism of cytotoxic action. Compounds D2&mdash;D4 are reported for the first time in this study. Except for Ig2 and D2, the cytotoxicity of mono-Mannich bases, Ig1, Ig3 and Ig4 and corresponding azine derivatives, D1, D3 and D4 were higher than the reference compound 5-FU. Azine derivatives D1 and D4 had almost equal cytotoxic potency with corresponding mono-Mannich bases Ig1 and Ig4, respectively. On the other hand, azine derivatives D2 and D3, had 1.28 and 1.90-times less cytotoxicity in Jurkat cells compared with the mono-Mannich bases, Ig2 and Ig3, respectively, from which they are derived. Azine derivative D3 dose-dependently decreased the total cellular glutathione level, suggesting that azine derivatives may exert cytotoxicity by thiol alkylation. Azine derivatives with equal or less cytotoxic potency compared to the mono-Mannich bases they are derived from seemed to be less suitable derivatives for the development of new cytotoxic compounds.

著者

Qiaomei Dai Meiqiao Wang Yaozhang Li Ji Li

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-00083, (Released:2019-04-23)

参考文献数

43

被引用文献数

11

---

To study the role of asarinin on collagen-induced arthritis (CIA) and its treatment mechanism on dendritic cells (DCs) and T cells. Before the onset of arthritis, asarinin were given orally to CIA mouse. Macroscopic scoring and micrometer caliper measurement were used to assess arthritis. The occurrence of cartilage destruction and bone erosion were assessed by histology of knee. Sandwich ELISA and PCR were used to assess the level of cytokines in hindpaw and arthritic joint. The CD11c MicroBeads were employed to isolate CD11c+ cells from the spleen. Quantitative PCR was used to determine DCs surface molecules of spleen. Macroscopic score and the frequency of arthritis were inhibited by asarinin. Swelling of hindpaws, inflammatory cell infiltration in the synovium, cartilage destruction, and bone erosion were delayed with asarinin. Asarinin treatment suppressed the expression of Th1 cytokines and increased the levels of Th2 cytokines (IL-10), TGF-β and Foxp3 in the synovium and hindpaw, however T-bet mRNA levels in synovium decreased. Lower expression of TLR9 and NF-kB were found in DCs after asarinin treatment. There was no difference in the expression of ICAM-1, OX40-L, and 4-1BBL in spleen DCs between the asarinin group and model control group. Asarinin can treat CIA. TLR9/NF-κB pathway may be involved in the asarinin treatment of CIA by skewing the balance of Th1/Th2/Treg to a Th2 type.

著者

Masahiko Imai Hiromasa Yokoe Masayoshi Tsubuki Noriko Takahashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b18-01002, (Released:2019-04-12)

参考文献数

14

被引用文献数

16

---

Cancer is the leading cause of death and there is a particularly pressing need to develop effective treatments for breast and prostate cancer. In the current study, we show the inhibitory effects of cinnamic acid derivatives, including caffeic acid phenethyl ester (CAPE, 1), on the growth of breast and prostate cancer cells. Among the compounds examined, 3,4,5-trihydroxycinnamic acid decyl ester (6) showed the most potent inhibition of cancer cell growth by the induction of apoptosis. Compound 6 could be a new anti-cancer agent for use against breast and prostate cancer.

著者

Weibin Du Chiharu Fukano Mari Yonemoto Tomokazu Matsuoka Keisuke Masuyama Katsuyo Ohashi-Doi

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.4, pp.601-606, 2019-04-01 (Released:2019-04-01)

参考文献数

29

被引用文献数

5

---

Subcutaneous allergen immunotherapy (SCIT) with non-standardized house dust (HD) extracts has been used in Japan since 1963 for house dust mite (HDM)-allergic patients. Since the potencies of HD extracts are unknown, the allergenic potency of HD extracts was examined by comparing with a standardized HDM allergen extracts. The major allergen content of HDM in the extracts was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). The immunoglobulin E (IgE) inhibitory activities of the extracts were measured by a competitive ELISA. The extract concentrations giving 50% inhibition of IgE binding (log10 IC50) were determined from dose–response curves and defined as inhibitory activities. A linear regression line was constructed from the log10 IC50 values of the standardized HDM extract to interpolate the relative potency of the HD extract with strength of 1 : 10 w/v (HD 1 : 10). The amounts of major allergens (Der f 1, Der p 1 and Der 2) were 116.3 µg/mL in the HDM allergen extract (100000 Japanese Allergy Units [JAU]/mL) and 0.77 µg/mL in the HD 1 : 10. The inhibitory activity (log10 IC50 values) of HD 1 : 10 was 2.389 ± 0.078, indicating the allergenic potency was between 200 and 2000 JAU/mL. Based on regression analysis (R2 >0.99), the allergenic potency of HD 1 : 10 was estimated to be 842 ± 128 JAU/mL. The present study determined the major allergen content of HD extract, which contributes to its allergenic potency. The allergenic potency of HD 1 : 10 was ca. 100-fold less than that of HDM allergen extract.

著者

Kazunari Iwao Rushiana Tokie Kawai Masako Oda Hiroshi Saitoh

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.9, pp.1566-1571, 2017-09-01 (Released:2017-09-01)

参考文献数

23

被引用文献数

1

---

The objective of this study was to evaluate the interactions between various drugs and aojiru (green juice), a popular health food in Japan, using a simple centrifugation method. The mixture of drug solution and aojiru suspension was gently shaken and centrifuged. The drug concentration in the supernatant fluid was then determined by HPLC. The concentration of rhodamine 123 (Rho-123), a model compound, in the supernatant fluid significantly decreased after mixing with aojiru, indicating extensive binding of Rho-123 to the insoluble components of aojiru. When administered into rat small intestinal loops together with aojiru, the plasma Rho-123 concentrations became much smaller than those when administered alone. This result strongly suggested that a strong interaction observed in vitro was well reflected in modulated absorption. Among seven drugs tested, chlorpromazine and imipramine exerted binding properties to aojiru similar to or greater than Rho-123. As a small part of both Rho-123 and imipramine was released when the aojiru precipitate was resuspended, their binding to aojiru was considered to be tight. The binding of diltiazem, fexofenadine, glibenclamide, metformin, and norfloxacin to aojiru was much weaker or almost negligible compared with that of chlorpromazine and imipramine. The present results suggest that aojiru can decrease the intestinal absorption of some clinically relevant drugs through tight binding in the small intestine and that the present centrifugation method is useful for predicting in vivo interactions between drugs and aojiru.

著者

佐藤 哲男 細川 正清 渥美 亮 鈴木 亘 伯水 英夫 永井 栄一

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.5, pp.662-664, 1994-05-15 (Released:2008-04-10)

参考文献数

18

被引用文献数

79 131

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We measured the plasma concentrations of 7-ethyl-10-[4-(1-piperidino)-1-piperidine] carbonyloxycamptothecin (CPT-11) and the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), after treatment with CPT-11 to rats pretreated with bis-p-nitrophenylphosphate (BNPP) which is a specific inhibitor of carboxylesterase, and non-pretreated rats. The plasma level of SN-38 was decreased in the BNPP-pretreated group compared with these of non-pretreated group, indicating that the esterase involved in CPT-11 metabolism is a carboxylesterase. We also characterized the molecular species of carboxylesterase involved in CPT-11 metabolism using enzyme preparations purified from liver microsomes. Thirteen carboxylesterase isozyme activities towards CPT-11 were compared and guinea pig GLP1 was found to have the highest activity, while human HU1 isozyme had relatively lower activity than those of animal species. In studies on the kinetic parameters of the hydrolysis of CPT-11 by the purified carboxylesterase isozymes the highest Vmax value of the isozymes was found in human HU1 and the smallest was seen in rat RL1. The Vmax/Km for RL1 showed the largest value of 21.7 nmol/mg protein/mM.

著者

藤田 靖之 八重樫 隆 澤田 誠吾 尾山 廣 芳本 忠 鶴 大典

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.5, pp.648-652, 1995-05-15 (Released:2008-04-10)

参考文献数

22

被引用文献数

5 5

---

A hydrolytic enzyme which catalyzes hydrolysis of the ester-linkage of a series of 17-O-acyl derivatives of 7-ethylcamptothecin-21-(2-dimethylamino) ethylamide [acyl derivatives of 22E] was purified from rat liver and its properties were characterized. It hydrolyzed the ester-linkage of all 22E derivatives tested as well as p-nitrophenyl acetate at pH 8-9 but had no effect on 7-ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11 : irinotecan), unlike CPT-11 converting carboxylesterase, which was previously purified from rat serum [Tsuji T. et al., J. Pharmacobio-Dyn., 14, 341 (1991)]. The enzyme had no effect on either acetyl choline or butyrylcholine. It was inhibited by several organophosphorous compounds such as diisopropyl fluorophosphate (DFP), bis-(pnitrophenyl) phosphate and paraoxon, but was insensitive to inhibitors specific for choline esterases. These results indicate that this liver esterase is clearly distinct from choline esterase and serum CPT-11 converting enzyme and is able to convert pro-drugs, O-acyl derivatives of 22E, to an antitumor agent.

著者

Nanami Shigetomi Kenta Kamiya Toru Takamori Naoki Yoshimura Sayaka Ozawa Keiichi Hirono Fukiko Ichida Masato Taguchi

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.1, pp.110-115, 2019-01-01 (Released:2019-01-01)

参考文献数

23

被引用文献数

2

---

The purpose of this study was to determine the serum protein binding of tadalafil in children with protein-losing enteropathy (PLE) and to evaluate the specific binding of the drug to human serum-derived proteins in vitro. Seventeen serum samples from two PLE patients used after biochemical tests were collected, and the unbound fraction of tadalafil was determined by an ultrafiltration method. The serum albumin concentrations observed in patients #1 and #2 were 2.4–4.2 and 2.9–3.5 g/dL, respectively. The ranges of unbound fraction of tadalafil in patients #1 and #2 were 3.9–13 and 5.0–7.0%, respectively. This suggested that serum albumin was at least a binding carrier for tadalafil because the unbound fraction of tadalafil and serum albumin were slightly correlated. The unbound fraction of tadalafil at the total concentration of 300 ng/mL was negatively dependent on the serum albumin concentration (range: 1.0–5.0 g/dL) in vitro. In the presence of albumin, the additive effect of γ-globulin on the unbound fraction of tadalafil was marginal, but the addition of α1-acid glycoprotein to test samples decreased the unbound fraction of the drug. The decrease in the unbound fraction of tadalafil was greater at low albumin levels (2 g/dL). The addition of lipoprotein to test samples also decreased the unbound fraction of tadalafil, suggesting that lipoprotein was also a binding carrier of the drug. These results suggested that the disposition and/or response to tadalafil in PLE patients was altered by the change in protein bindings of the drug.

著者

Kosuke Shimizu Miki Takada Tomohiro Asai Kenji Irimura Kazuhiko Baba Naoto Oku

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.6, pp.783-786, 2002 (Released:2002-06-01)

参考文献数

19

被引用文献数

10 13

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To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4β-aminoalkyl-4′-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.

著者

Naoto Okada Kazuyoshi Kawazoe Kazuhiko Teraoka Toshihide Kujime Masahiro Abe Yasuo Shinohara Kazuo Minakuchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.10, pp.1622-1626, 2013-10-01 (Released:2013-10-01)

参考文献数

21

被引用文献数

27 42

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Denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand, inhibits the activation of osteoclasts. Some clinical trials have shown that denosumab suppresses bone resorption in patients with advanced cancer, but hypocalcemia has been reported as a serious adverse effect after the administration of denosumab. It is difficult to predict hypocalcemia in such cases because the risk factors for denosumab-induced hypocalcemia have not been reported. Accordingly, the aim of the present study was to identify the risk factors for hypocalcemia induced by denosumab. We retrospectively reviewed the records of patients who had received denosumab at Tokushima University Hospital between April 2012 and May 2013. Fifty-three patients were analyzed and eleven patients had hypocalcemia after administration of denosumab. Univariate logistic regression analysis revealed that the patients who had not been administered zoledronic acid before receiving denosumab or had lower creatinine clearance (CCr) appeared to have a higher risk of hypocalcemia (p<0.05). The cut off value of CCr was 50.4 mL/min calculated by receiver-operator characteristics curves. Moreover, multivariate logistic regression analysis revealed that non-administration of zoledronic acid (odds ratio 10.43, p<0.05) and CCr less than 50.0 mL/min (odds ratio 5.90, p<0.05) were independent risk factors for denosumab-induced hypocalcemia. These findings provide useful information regarding the monitoring of hypocalcemia in patients receiving denosumab.

著者

Jiang Saho Jun Zhou Xiao Jun

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.1, pp.66-68, 2003-01-01

参考文献数

16

被引用文献数

1 39

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The epidermal permeability barrier appears to be regulated primarily by the lamellar arrangement of lipid bilayers between coneocytes of the stratum corneum and presents a significant barrier to the transdermal delivery of drugs. The aim of the present study was to investigate the effects of oleic acid on the ultrastructure of stratum corneum lipids in rat skin. Wistar rats were treated topically with 10% oleic acid/propylene glycol for 2 h, the structure of stratum corneum was examined by electron microscopy using osmium tetroxide or ruthenium tetroxide postfixation, and the epidermal barrier function was evaluated in a lanthanum tracer study. Ultrastructural examination revealed that there was a marked alteration in the stratum corneum and the tracer penetrated into the intercellular spaces of the stratum corneum after application of oleic acid. These results suggest that ruthenium tetroxide postfixation is a powerful tool for the study of the stratum corneum lipid structure. Oleic acid might increase the epidermal permeability through a mechanism involving the perturbation of stratum corneum lipid bilayers and lacunae formation to enhance transdermal drug delivery.

著者

Congyun Jin Yoshiaki Yao Atsushi Yonezawa Satoshi Imai Hiroki Yoshimatsu Yuki Otani Tomohiro Omura Shunsaku Nakagawa Takayuki Nakagawa Kazuo Matsubara

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.11, pp.1990-1995, 2017-11-01 (Released:2017-11-01)

参考文献数

22

被引用文献数

13

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Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase.

著者

Aurpita Shaha Hiroyuki Mizuguchi Yoshiaki Kitamura Hiromichi Fujino Masami Yabumoto Noriaki Takeda Hiroyuki Fukui

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.9, pp.1440-1447, 2018-09-01 (Released:2018-09-01)

参考文献数

44

被引用文献数

23

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The significant correlation between nasal symptom scores and level of histamine H1 receptor (H1R) mRNA in nasal mucosa was observed in patients with pollinosis, suggesting that H1R gene is an allergic disease sensitive gene. We demonstrated that H1R and interleukin (IL)-9 gene are the allergic rhinitis (AR)-sensitive genes and protein kinase Cδ (PKCδ) signaling and nuclear factor of activated T-cells (NFAT) signaling are involved in their expressions, respectively. Honey bee products have been used to treat allergic diseases. However, their pathological mechanism remains to be elucidated. In the present study, we investigated the mechanism of the anti-allergic effect of royal jelly (RJ) and Brazilian green propolis (BGPP). Treatment with RJ and BGPP decreased in the number of sneezing on toluene 2,4-diissocyanate (TDI)-stimulated rats. The remarkable suppression of H1R mRNA in nasal mucosa was observed. RJ and BGPP also suppressed the expression of IL-9 gene. RJ and BGPP suppressed phorbol-12-myristate-13-acetate-induced Tyr311 phosphorylation of PKCδ in HeLa cells. In RBL-2H3 cells, RJ and BGPP also suppressed NFAT-mediated IL-9 gene expression. These results suggest that RJ and BGPP improve allergic symptoms by suppressing PKCδ and NFAT signaling pathways, two important signal pathways for the AR pathogenesis, and suggest that RJ and BGPP could be good therapeutics against AR.

著者

Jiangang Chen Wenfang Lu Hao Chen Xiaoli Bian Guangde Yang

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b18-00661, (Released:2018-11-30)

参考文献数

40

被引用文献数

3 10

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In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15 ± 0.01 mM, 0.086 ± 0.01 mM and 0.32 ± 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

著者

Kosuke Baba Reiko Hiramatsu Benjamart Suradej Riho Tanigaki Sayaka Koeda Tomonori Waku Takao Kataoka

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.12, pp.1757-1768, 2018-12-01 (Released:2018-12-01)

参考文献数

45

被引用文献数

1 10

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The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus. In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1. In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface. Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells. Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein. Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker). Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity. These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.

著者

Takashi Yamauchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.28, no.8, pp.1342-1354, 2005 (Released:2005-08-01)

参考文献数

129

被引用文献数

112 153

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Much has been learned about the activity-dependent synaptic modifications that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. A good candidate for the storage mechanism is Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). CaM kinase II is one of the most prominent protein kinases, present in essentially every tissue but most concentrated in brain. Although it has been about a quarter of a century since the finding, CaM kinase II has been of the major interest in the region of brain science. It plays a multifunctional role in many intracellular events, and the expression of the enzyme is carefully regulated in brain regions and during brain development. Neuronal CaM kinase II regulates important neuronal functions, including neurotransmitter synthesis, neurotransmitter release, modulation of ion channel activity, cellular transport, cell morphology and neurite extension, synaptic plasticity, learning and memory, and gene expression. Studies concerning this kinase have provided insight into the molecular basis of nerve functions, especially learning and memory, and indicate one direction for studies in the field of neuroscience. This review presents the molecular structure, properties and functions of CaM kinase II, as a major component of neurons, based mainly developed on findings made in our laboratory.

著者

Hiroaki KUBO Tasashi OSAWA Kohki TAKASHIMA Masakazu MIZOBE

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.19, no.5, pp.741-747, 1996-05-15 (Released:2008-04-10)

参考文献数

17

被引用文献数

27 29

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To improve the bioavailability of the sparingly water-soluble drug, 1-(3, 4-dimethoxyphenyl)-2, 3-bis(methoxycarbonyl)-4-hydroxy-6, 7, 8-trimethoxynaphthalene (TA-7552), the usefulness of the co-grinding method with D-mannitol was investigated. The co-grinding was performed at various weight ratios of TA-7552 and D-mannitol using a ball mill. The particle size was markedly reduced with increasing amount of D-mannitol. A mixture ratio greater than or equal to 1 : 3 of the drug and D-mannitol produced submicron-sized particles. In dogs, bioavailability increased with increasing amount of D-mannitol. The 1 : 9 coground mixture gave complete absorption, as did a lecithin solution of the drug. Even co-ground powders with lower amounts of D-mannitol provided relatively high bioavailability in comparison with ground drug powder alone of a similar particle size. Further, pharamacological examination using rats indicated that the inhibition of cholesterol absorption was intestified with the reduction of particle size. These findings suggest that the co-grinding method with D-mannitol is useful for enhancing the bioavailability and pharmacological effectiveness of this sparingly water-soluble drug.