著者
Satoshi Yamaori Yoshimi Okushima Kazufumi Masuda Mika Kushihara Takashi Katsu Shizuo Narimatsu Ikuo Yamamoto Kazuhito Watanabe
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.36, no.7, pp.1197-1203, 2013-07-01 (Released:2013-07-01)
参考文献数
39
被引用文献数
2 11

Our recent work has shown that cannabidiol (CBD) exhibits the most potent direct inhibition of human cytochrome P450 1A1 (CYP1A1) among the CYP enzymes examined. However, the mechanism underlying this CBD inhibition remains to be clarified. Thus, to elucidate the structural requirements for the potent inhibition by CBD, the effects of CBD and its structurally related compounds on CYP1A1 activity were investigated with recombinant human CYP1A1. Olivetol, which corresponds to the pentylresorcinol moiety of CBD, inhibited the 7-ethoxyresorufin O-deethylase activity of CYP1A1; its inhibitory effect (IC50=13.8 µM) was less potent than that of CBD (IC50=0.355 µM). In contrast, d-limonene, which corresponds to the terpene moiety of CBD, only slightly inhibited CYP1A1 activity. CBD-2′-monomethyl ether (CBDM) and CBD-2′,6′-dimethyl ether inhibited CYP1A1 activity with IC50 values of 4.07 and 23.0 µM, respectively, indicating that their inhibitory effects attenuated depending on the level of methylation on the free phenolic hydroxyl groups in the pentylresorcinol moiety of CBD. Cannabidivarin inhibited CYP1A1 activity, although its inhibitory potency (IC50=1.85 µM) was lower than that of CBD. The inhibitory effects of Δ9-tetrahydrocannabinol and cannabielsoin (IC50s ≈10 µM), which contain a free phenolic hydroxyl group and are structurally constrained, were less potent than that of CBDM, which contains a free phenolic hydroxyl group and is rotatable between pentylresorcinol and terpene moieties. These results suggest that the pentylresorcinol structure in CBD may have structurally important roles in direct CYP1A1 inhibition, although the whole structure of CBD is required for overall inhibition.
著者
大村 智
出版者
公益社団法人日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.42, no.10, pp.979-983, 2006-10-01
参考文献数
11
著者
大橋 一智 上田 浩史 山崎 正利 木村 貞夫 安部 茂 山口 英世
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 (ISSN:00316903)
巻号頁・発行日
vol.112, no.12, pp.919-925, 1992-12-25
被引用文献数
19

The biological activity of a preparation of heat killed cells of Enterococcus faecalis, FK-23 which was isolated from the feces of a healthy human, was investigated in C3H/He mice. Intraperitoneal injection of the preparation caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice 6 h later. As a parameter of the activation of macrophages, the effect of the FK-23 preparation on the production of tumor necrosis factor (TNF) was examined. The mice were given two consecutive intravenous injections of the preparation at a dose of 10μg/mouse and, 3 h later, of 300μg/mouse. The TNF level in the sera reached 99 U/ml in mice 2 h after the second injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro and increased the capacity of neutrophils to adhere to plastic plates and to release active oxygens, but did not induce blastogenic transformation of lymphocytes. These results suggest that the FK-23 preparation is a biological response modifier (BRM) with various activities on phagocytes similar to a streptococcal antitumor agent, OK432.
著者
手塚 雅勝 鈴木 弘美 鈴木 康夫 原 征彦 岡田 昌二
出版者
公益社団法人日本薬学会
雑誌
衛生化学 (ISSN:0013273X)
巻号頁・発行日
vol.43, no.5, pp.311-315, 1997-10-31
参考文献数
13
被引用文献数
10

The effects of catechins obtained from the hot water extract of green tea leaves on two human type-A influenza virus strains of Aichi/2/68 and PR/8/34 were studied. In this study, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin gallate (EGCg), the crude catechins containing these catechins and (+)-catechin were used. Consequently it was observed that catechins used in this study had an inhibitory effect on the hemolytic activity to red blood cells induced by these two type-A virus strains under acidic conditions (pH 5.1 or 5.4) although they did not have an influence on the agglutination activity to red blood cells induced by the same virus strains. After incubation of (-)-ECg and (-)-EGCg with A/Aichi/2/68 virus, MDCK cells, virus-sensitive cells, were infected with the virus and the ability of virus proliferation was measured in terms of an index of the agglutination activity of the virus to red blood cells. The used two catechins, (-)-ECg and (-)-EGCg, inhibited the virus proliferation at concentrations of 100μg/ml and 50μg/ml, respectively. Furthermore, at a concentration of 2.0 mg/ml these two catechins were found to inhibit the activity of neuraminidase on the surface of the virus membrane by 71.3% and 60.8%, respectively. From the above-mentioned results, it is considered that among the catechins contained in green tea leaves, such two catechins as (-)-ECg and (-)-EGCg inhibit the activity of neuraminidase present on the surface of human influenza virus in order to block the invasion of the influenza virus into virus-sensitive cells.
著者
野口 照久 原 博
出版者
公益社団法人日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.32, no.1, pp.19-23, 1996-01-01
著者
乙黒 一彦
出版者
公益社団法人日本薬学会
雑誌
ファルマシア (ISSN:00148601)
巻号頁・発行日
vol.41, no.6, pp.551-554, 2005-06-01
著者
JaeHo Lee SeungJun Lee ByungMan Lee KyungBaeg Roh DeokHoon Park EunSun Jung
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b15-00305, (Released:2015-07-15)
参考文献数
14
被引用文献数
4

For screening of skin-whitening ingredients that modulate inhibition of melanogenesis, tyrosinase promoter-based assay using a 3D spheroid culture technique is a beneficial tool to improve the accuracy of raw material screening in cosmetics through mimicking of the in vivo microenvironment. Although the advantages of high-throughput screening (HTS) are widely known, there has been little focus on specific cell-based promoter assays for HTS in identifying skin-whitening ingredients that inhibit accumulation of melanin. The aim of this study was therefore to develop a large-scale compatible assay through pTyr-EGFP, an enhanced green fluorescent protein (EGFP)-based tyrosinase-specific promoter, to seek potential melanogenesis inhibitors for cosmetic use. Herein, a stably transfected human melanoma cell line expressing EGFP under the control of a 2.2-kb fragment derived from the tyrosinase gene was generated. Spontaneous induction of the tyrosinase promoter by 3D spheroid culture resulted in increased expression of EGFP, providing a significant correlation with the tyrosinase mRNA level, and subsequent inhibition of tyrosinase activity. Importantly, the pTyr-EGFP system provided successful tracking of the changes in the live image and real-time monitoring. Thus tyrosinase promoter-based fluorescent assay using a 3D spheroid culture can be useful as a screening system for exploring the efficiency of anti-melanogenesis ingredients.
著者
Kiyosei Takasu
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.64, no.7, pp.656-667, 2016-07-01 (Released:2016-07-01)
参考文献数
68
被引用文献数
1 9

The search for new drugs that could treat tropical protozoan diseases, such as malaria or neglected tropical diseases (NTDs), motivates many medicinal chemists. New classes of antiprotozoal drugs that act through a novel mechanism of action must be developed. This review presents our efforts toward finding new candidate treatments for malaria, American trypanosomiasis, human African trypanosomiasis and leishmaniasis based on π-delocalized lipophilic cations (DLCs). DLCs, such as rhodacyanines, azarhodacyanines, β-carbolinium salts, and phenoxazinium salts, displayed strong antiprotozoal activities with highly selective indices. Several DLCs displayed moderate to excellent in vivo efficacies against Plasmodium berghei when administered intraperitoneally or orally. This review also discusses chemical biology approaches to understanding the mechanism of action underlying the antimalarial rhodacyanines.
著者
Annie Shirwaikar Arun Shirwaikar Kuppusamy Rajendran Isaac Sam Raj Punitha
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.29, no.9, pp.1906-1910, 2006 (Released:2006-09-01)
参考文献数
39
被引用文献数
85 171

Berberine is a benzyl tetra isoquinoline alkaloid which is widely used as an antimicrobial and an antidiarrhoeal. As berberine containing plants are virtually used in all forms of traditional medicine, our study aimed to examine the antioxidant activity of berberine using 2,2-diphenyl 1-picrylhydrazyl (DPPH) radical scavenging, nitric oxide scavenging, lipid peroxidation, superoxide scavenging, iron chelating activity and 2,2-azino bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging methods. The IC50 values for all the models were calculated by regression analysis. In all the models tested, berberine showed its ability to scavenge the free radicals in a concentration dependent manner. The present study thereby justifies the therapeutic potential of berberine.
著者
千原 呉郎
出版者
公益社団法人日本薬学会
雑誌
藥學雜誌 (ISSN:00316903)
巻号頁・発行日
vol.108, no.3, pp.171-186, 1988
被引用文献数
6 7

The most important problem in cancer research is to increase comfortably the survival time and to prevent completely recurrence after surgical resection in cancer patients. Cytocidal anticancer chemotherapeutics have detrimental side effects and destroy host defence mechanisms, and are not useful for cancer patients. On the other hand, there is several evidence suggesting the existence of intrinsic resistance to cancer. The examples are an equilibrium state with proliferation and regression in a small amount of cancer cells and spontaneous regression of cancer. An increase in this resistance may be one of the most important problem to find new anticancer drugs. In Oriental medicine practiced in Asian countries from olden times, the fundamental principle is to regulate homeostasis of the whole body and to bring the diseased person to a normal state, rather than to attack the focus directly. On the basis of such a concept, the antitumor activity of numerous folk remedies has been reexamined and isolated a polysaccharide with marked antitumor activity and named as lentinan. Lentinan is a strictly purified β-1, 6 : β-1, 3-D-glucan, and exerts prominent antitumor activities in murine allogeneic, syngeneic and autochthonous hosts, prevents chemical and viral oncogeneses, and suppresses tumor metastasis in several clinical models. The antitumor action of lentinan is host-mediated. Comparing with other well-known immunostimulants, such as BCG, C. parvum and LPS, lentinan appears to represent a unique class of immunopotentiator, a T-cell oriented adjuvant in which macrophages play some parts. First, lentinan triggers the increased production of various kinds of bioactive serum factors associated with immunity and inflammation, such as CSF, IL-1, IL-3, vascular dilatation hemorrhage inducer and acute-phase protein inducer, by direct impact of macrophages or indirectly via lentinan-stimulated T-cells, which results in the induction of many immunobiological changes in the host. Augmented IL-1 production amplifies the maturation of immature effector cells to mature cells capable of responding to IL-2 and other cytokines, but lentinan do not augment production of IL-2. This is the most important characteristics of lentinan, because this suggests a contact point between new immunology and Oriental medicine. Lentinan augments differentiation of various kinds of important cells in the host defence. These results clearly explain the requirment of intact macrophages and T-cell compartments for antitumor activity of lentinan. Lentinan has only a little toxic side effect in in vivo application to animals and human. An excellent result was obtained in 4 year's follow-up of the randomized control study of lentinan in Phase III on the patients with advanced and recurrent stomach, colo-rectal, breast cancer and malignant lymphoma. These results suggest that lentinan might be more effective for micrometastasis after surgery. Lentinan is a hopeful drug for cancer patients.
著者
Yusuke Watanabe Yuji Ikegaya
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.40, no.7, pp.1111-1115, 2017-07-01 (Released:2017-07-01)
参考文献数
28
被引用文献数
3

Caffeine promotes memory consolidation. Memory consolidation is thought to depend at least in part on hippocampal sharp waves (SWs). In the present study, we investigated the effect of bath-application of caffeine in spontaneously occurring SWs in mouse acute hippocampal slices. Caffeine induced an about 100% increase in the event frequency of SWs at concentrations of 60 and 200 µM. The effect of caffeine was reversible after washout of caffeine and was mimicked by an adenosine A1 receptor antagonist, but not by an A2A receptor antagonist. Caffeine increased SWs even in dentate-CA3 mini-slices without the CA2 regions, in which adenosine A1 receptors are abundantly expressed in the hippocampus. Thus, caffeine facilitates SWs by inhibiting adenosine A1 receptors in the hippocampal CA3 region or the dentate gyrus.
著者
Kazuma Higashisaka Kazuya Nagano Yasuo Yoshioka Yasuo Tsutsumi
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.40, no.3, pp.243-248, 2017-03-01 (Released:2017-03-01)
参考文献数
61
被引用文献数
22

In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now an important part of our daily lives. Despite our increasing exposure to nanoparticles, however, information regarding the absorption, distribution, metabolism, excretion, and toxicity of nanoparticles remains limited. In this review, we introduce our group’s ongoing research into the biological effects and toxicities of nanoparticles, which we broadly refer to as “nano-safety research.” In addition to determining the biological effects of nanoparticles and elucidating the underlying mechanisms of those effects, we are also exploring the associations among the physicochemical properties and kinetics of nanoparticles. Furthermore, we are currently developing a battery of biomarkers that we hope will be used to predict the biological effects of nanoparticles during the early stages of development. Our research provides valuable basic information on the safety of nanoparticles. We hope that this information will be used for the development of better assessments of nanoparticles safety and for the creation of more appropriate regulations to ensure not only the safety but also the sustainability of nanotechnology.
著者
Hironori Takeuchi Yoshihiro Ueda Takumi Furuta Takeo Kawabata
出版者
公益社団法人日本薬学会
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.65, no.1, pp.25-32, 2017-01-01 (Released:2017-01-01)
参考文献数
27
被引用文献数
14

A short-step total synthesis of the natural glycosides pterocarinin C and tellimagrandin II (eugeniin) has been performed by sequential and site-selective functionalization of free hydroxy groups of unprotected D-glucose. The key reactions are β-selective glycosidation of a gallic acid derivative using unprotected D-glucose as a glycosyl donor and catalyst-controlled site-selective introduction of a galloyl group into the inherently less reactive hydroxy group of the glucoside.
著者
Hideharu Maruta Naoyuki Okita Ryoko Takasawa Fumiaki Uchiumi Tsutomu Hatano Sei-ichi Tanuma
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.30, no.3, pp.447-450, 2007 (Released:2007-03-01)
参考文献数
34
被引用文献数
9 20

The formation of ATP produced from poly(ADP-ribose) [(ADP-R)n] has been suggested to be required to repair damaged DNA. Here we investigate whether this ATP is involved in DNA replication processes during DNA repair. Poly(ADP-ribosyl)ated mid-S phase cell nuclei, which were isolated from synchronized HeLa S3 cells followed by the treatment with a DNA damaging agent, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), were revealed to retain DNA replication synthesizing activity during preincubation for de-poly(ADP-ribosyl)ation only in the presence of pyrophosphate (PPi) before DNA synthesis was started by adding 3 mM ATP. This DNA replication activity was not maintained in the presence of a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase (PARG), Oenothein B (Oen B) during the preincubation with PPi. In the preincubation with PPi, μM orders of ATP was produced from (ADP-R)n. These results point to an important function of ATP generated from (ADP-R)n in nuclei for the maintenance of replication apparatus during DNA repair.
著者
Sat Byul Park Kyu-Nam Kim Eunju Sung Suk Young Lee Ho Cheol Shin
出版者
公益社団法人日本薬学会
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
pp.b15-00623, (Released:2016-02-25)
参考文献数
25
被引用文献数
6

Chronic Fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of seventy eight subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the Fatigue Severity Scale (FSS), Visual Analog Scale (VAS) and Multidimensional Fatigue Inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p= 0.0242), VAS (p =0.0009) and MFI (p= 0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.
著者
久保寺 昭子 毛利 哲郎 鶴藤 丞
出版者
公益社団法人日本薬学会
雑誌
薬学雑誌 (ISSN:00316903)
巻号頁・発行日
vol.87, no.5, pp.511-515, 1967-05

Effect of 10 chelating agents on the excretion of radiostrontium from the body was investigated in mice. Sodium salts and/or monocalcium-sodium salts of these chelating agents were used as test materials. Preliminery toxicity tests were carried out to estimate their approximate maximum safety doses. The sodium salts were generally more toxic and brought about some convulsion with occasional death which were attributed to the decrease of Ca^<2+> ion in the blood. The monocalcium-sodium salts were applicable in 10-folds as compared with their equivalent sodium salts. The chelating agents and radioactive strontium were simultaneously injected into different parts of the body. The animals were killed 24 hours after the injection, and then reduced to ashes individually in an electric furnace after removing the digestive tracts and bladders. Radioactivity of the ashes was assayed to determine the percentage retention of radioactive strontium in the carcasses. Monocalcium-disodium salt of bis(dicarboxyaminoethyl) ether was found to be one of the most effective agents, same as calcium sodium citrate which had been previously reported.