著者

Makoto Urai Keiko Kataoka Satoshi Nishida Kazuhisa Sekimizu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.11, no.5, pp.230-237, 2017-10-31 (Released:2017-11-22)

参考文献数

22

被引用文献数

7

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Vegetables are eaten as part of a healthy diet throughout the world, and some are also applied topically as a traditional medicine. We evaluated the innate immunostimulating activities of hot water extracts of various vegetables using the silkworm muscle contraction assay system, and found that broccoli, Brassica oleracea var. italica, contains a strong innate immunostimulant. We purified the innate immunostimulant from broccoli, and characterized the chemical structure by chemical analyses and NMR spectroscopy. The innate immunostimulant comprised galacturonic acid, galactose, glucose, arabinose, and rhamnose, and had a pectic-like polysaccharide structure. To determine the structural motif involved in the innate immunostimulating activity, we modified the structure by chemical and enzymatic treatment, and found that the activity was attenuated by pectinase digestion. These findings suggest that a pectic-like polysaccharide purified from broccoli has innate immune-stimulating activity, for which the polygalacturonic acid structure is necessary.

著者

Mohammad M. Rahman Mayra A. Machuca Anna Roujeinikova

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.13, no.1, pp.52-58, 2019-02-28 (Released:2019-03-16)

参考文献数

46

被引用文献数

1

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Periplasmic binding proteins (PBPs) of Gram-negative bacteria sense essential nutrients and mediate their uptake by ATP-binding cassette (ABC) transporters. The gene for a PBP of H. pylori SS1, annotated as GlnH, is located within the glnPQH operon encoding an ABC importer system. In this study, GlnH has been expressed in E. coli and purified to > 98% homogeneity. The recombinant protein was folded according to the circular dichroism (CD) analysis and behaved as a monomer in solution. Crystals of GlnH have been grown by the hanging-drop vapour-diffusion method using polyethylene glycol (PEG) 4000 as a precipitating agent. The crystals belonged to the primitive monoclinic space group P21 with unit cell parameters a = 38.67, b = 93.36, c = 64.13 Å, β = 93.72°. A complete X-ray diffraction data set was collected to 1.3 Å resolution from a single crystal using synchrotron radiation. Molecular replacement using this data revealed that the asymmetric unit contains a single molecule. This is a key step towards elucidation of the structural basis of the GlnH function.

著者

Xinke Zhang Peng Li Shaohua Guo Shuqi Wang Dasheng Liu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.12, no.6, pp.341-346, 2018-12-31 (Released:2019-01-24)

参考文献数

13

被引用文献数

8

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Plant invasion is one of the major threats to natural ecosystems. The alligator weed grows rapidly within a small span of time and is easily available all over the world. β-Carboline and quercetin are considered as excellent bioactive components of the alligator weed. In our study LC-MS/MS methods were performed for the detection and determination of the bioactive constituents, ꞵ-carboline and quercetin in leaves, in multiple reaction monitoring (MRM) mode. The effects of methanol extract on cardiomyocyte apoptosis induced by doxorubicin using H9c2 cells were evaluated by MTT assay and Annexin V-FITC/PI staining assay. A sensitive and selective liquid chromatography tandem mass spectrometry was developed and validated for the determination of ꞵ-carboline and quercetin in this plant. According to in vitro cell evaluation experiments, methanol extracts significantly prevented cardiomyocyte apoptosis induced by doxorubicin.

著者

Jeremy Duncan Shakevia Johnson Xiao-Ming Ou

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.6, no.3, pp.112-122, 2012-06-30 (Released:2014-06-13)

参考文献数

82

被引用文献数

2 12

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Monoamine oxidases play an integral role in brain function. Both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) regulate neurochemistry by degrading monoamine neurotransmitters (serotonin, dopamine, and norepinephrine). Any alteration in MAO levels can have devastating effects on the brain and behavior by lowering or raising neurotransmitter levels and producing toxic reactive oxygen species. In this review article, MAO is examined in terms of function and genetic organization, with special focus on recent discoveries related to the transcriptional regulation of MAO. In recent studies, transcriptional regulation involves a repressor protein, R1, for MAO-A and an activator protein, KLF11 (a Krüppel-like factor; also referred to as transforming growth factor-beta early inducible gene 2, TIEG2), for both MAO-A and MAO-B, by binding to Sp/KLF sites in the core promoters of MAO and regulating MAO gene expression. Furthermore, KLF11 may influence MAO-B expression and augment glyceraldehyde-3 phosphate dehydrogenase (GAPDH) to upregulate MAO-B transcription upon exposure to ethanol. Finally, we review recent progress in MAO research and highlight the roles that MAOs play in several psychiatric conditions, including chronic stress, major depressive disorder and alcohol dependence. Further research in this area is needed to better understand MAOs, their transcription factors and signaling pathways in psychiatric illnesses in order to develop new strategies for pharmacological advancement.

著者

Guohua Han Jufeng Xia Jianjun Gao Yoshinori Inagaki Wei Tang Norihiro Kokudo

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.9, no.1, pp.1-12, 2015-02-28 (Released:2015-03-18)

参考文献数

88

被引用文献数

29 78

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Resveratrol (3, 5, 4'-trihydroxystilbene) is a phytoalexin contained in a variety of plants, such as grapes, berries and especially in the dried roots of Polygonum cuspidatum Sieb. et Zucc. It has been shown to exhibit anti-oxidative and anti-inflammation activity, and to reverse the effects of aging. Its ability to suppress cell proliferation, induce apoptosis and suppress the metastasis and invasion in a number of cell lines has prompted a large interest from people for its use as an anti-tumor component. In this review, evidence of resveratrol's anti-tumor effects and molecular mechanisms are recapitulated. First, we present the anti-apoptosis, anti-invasion/metastasis and anti-inflammation effect of resveratrol; second, the main signaling pathways involved in these activities are described and summarized with the studies of different tumors involved. Resveratrol not only induces apoptosis of tumor cells through intrinsic/extrinsic pathways and cell cycle arrest, but also inhibits the invasion and metastasis abilities of tumors via modulating collagen degradation-related molecular targets. Altogether, the present findings suggest the anti-tumor potential of resveratrol against various types of cancers.

著者

Satoshi Nishida Yasuo Ono Kazuhisa Sekimizu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.10, no.1, pp.49-56, 2016 (Released:2016-03-12)

参考文献数

34

被引用文献数

4 27

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Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products. We selected a highly active LAB to activate the innate immunity in silkworm by using the silkworm muscle contraction assay, as well. The assay revealed that Lactococcus lactis 11/19-B1 was highly active on the stimulation of the innate immunity in silkworm. L. lactis 11/19-B1 solely fermented milk with casamino acid and glucose. This strain would be a starter strain to make yogurt. Compared to commercially available yogurt LAB, L. lactis 11/19-B1 has higher activity on silkworm contraction. Silkworm normally ingested an artificial diet mixed with L. lactis 11/19-B1 or a yogurt fermented with L. lactis 11/19-B1. Interestingly, silkworms that ingested the LAB showed tolerance against the pathogenicity of Pseudomonas aeruginosa. These data suggest that Lactococcus lactis 11/19-B1 would be expected to be useful for making yogurt and probiotics to activate innate immunity.

著者

Mitsuru Nozawa Miho Goto Yuko Wada Miyuki Kumazawa Ken-ichi Shimokawa Fumiyoshi Ishii

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.12, no.1, pp.16-20, 2018-02-28 (Released:2018-03-19)

参考文献数

16

被引用文献数

4

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We measured and compared the physicochemical properties (pH, yield value, and squeeze force) of a drug for dermatomycosis, terbinafine hydrochloride-containing cream (brand-name product), and 12 generic products to clarify the characteristics of each product. On pH measurement, the pH value of the brand-name product, Lamisil, was 4.8, and those of the generic products ranged from 4.3 to 5.5, showing no marked difference. Furthermore, the yield value of Lamisil, as an index of cream ductility, was 122.2 dyn/cm2, and those of the generic products ranged from 42.1 to 1,621.5 dyn/cm2. In particular, the value of a generic product, Taiyo (42.1 dyn/cm2), was significantly lower, whereas that of another one, Viras (1,621.0 dyn/cm2), was significantly higher. In addition, the squeeze force was measured by attaching a HapLog® to the thumb and second finger. The value of Lamisil was 12.9 N, and those of the generic products ranged from 8.0 to 15.4 N. The values of generic products, Mylan (8.6 N), Tebinaceil (9.0 N), and Kelger (8.0 N), were significantly lower, whereas that of another one, Viras (15.4 N), was significantly higher. These results showed that there were marked differences in the pharmaceutical properties between the generic and brand-name products. The above pharmaceutical characteristics of drugs facilitated the presentation of reasons for differences in the sense of use, which characterizes external preparations, suggesting that products appropriate for individual patients can be recommended.

著者

Yuko Wada Yukie Takaoka Mitsuru Nozawa Miho Goto Ken-ichi Shimokawa Fumiyoshi Ishii

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.10, no.6, pp.300-306, 2016 (Released:2017-01-15)

参考文献数

16

被引用文献数

6

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We measured the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time of medicinal and over-the-counter (OTC) tape preparations containing felbinac. When measuring the pH of each preparation, Felnabion (pH 4.5) was weakly acidic, and EMEC and Tokuon (pH 7.0) were neutral. When measuring the water-vapor permeability of each preparation, that of a generic product, EMEC (380 g/m2/24h), was twice as high as that of a brand-name product, Seltouch (189 g/m2/24 h). The adhesive force was measured using the ball tack test. The adhesive forces of OTC drugs, Salomethyl, Homepass, and Tokuhon (1.04 g), were higher than that of Seltouch (0.06 g). Concerning peeling-force measurement, the peeling-forces of a generic product, Falzy (4.15 N), and an OTC drug, Omuneed (4.89 N), were higher than that of Seltouch (0.91 N). The elongation rates of a generic product, Sumilu (319%), and OTC drugs, Nabolin (298%) and Homepass (299%), were higher than that of Seltouch (251%), but that of Tokuhon (72%) was lower. The support flexibilities of EMEC (150 degrees) and Tokuhon (131 degrees) were higher than that of Seltouch (96 degrees). In addition, the peeling time of Seltouch was 120 min or more, whereas those of EMEC and Nabolin were 1.4 and 0.2 min, respectively. These results suggest that the differences in pharmaceutical properties, such as the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time, among the preparations markedly influence patients' subjective comfortableness. The results of this study facilitated individuals’ comfortableness-matched drug selection.

著者

Yasuhiko Matsumoto Kazuhisa Sekimizu

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.10, no.1, pp.14-18, 2016 (Released:2016-03-12)

参考文献数

26

被引用文献数

6

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Silkworm shows hyperglycemia after intake of diet containing large amount of glucose. The hyperglycemic silkworm model is useful for evaluation of anti-diabetic drugs. A hot water extract of Rehmanniae Radix, an herbal medicine, showed hypoglycemic effect against the hyperglycemic silkworms. This method is applicable for quick and simple evaluation of the hypoglycemic activities of different batches of Rehmanniae Radix. Our findings suggest that silkworms have a lot of merit as experimental animals for evaluation of various herbal medicines.

著者

Rima Salama Jintana Sattayasai Arun Kumar Gande Nison Sattayasai Mike Davis Eric Lattmann

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.6, no.1, pp.18-23, 2012-02-29 (Released:2014-06-13)

参考文献数

12

被引用文献数

1

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The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydro-andrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

著者

Atsushi Miyashita Yuuki Hirai Kazuhisa Sekimizu Chikara Kaito

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

pp.2015.01000, (Released:2015-01-25)

参考文献数

11

被引用文献数

2 16

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The search for new antibiotics or antifungal agents is crucial for the chemotherapies of infectious diseases. The limited resource of soil bacteria makes it difficult to discover such new drug candidate. We, therefore, focused on another bacterial resource than soil bacteria, the microbial flora of insect species. In the present study, we isolated 40 strains of bacteria and fungi from the mycangia of three species of stag beetle, Dorcus hopei binodulosus, Dorcus rectus, and Dorcus titanus pilifer. We identified those species with their ribosomal DNA sequences, and revealed that Klebsiella spp. are the most frequent symbiont in the stag beetle mycangia. We examined whether these microorganisms produce antibiotics against a Gram-negative bacterium, Escherichia coli, a Gram-positive bacterium, Staphylococcus aureus, or a fungus, Cryptococcus neoformans. Culture supernatants from 33, 29, or 18 strains showed antimicrobial activity against E. coli, S. aureus, or C. neoformans, respectively. These findings suggest that bacteria present in the mycangia of stag beetles are useful resources for screening novel antibiotics.

著者

Jufeng Xia Jianjun Gao Yoshinori Inagaki Norihiro Kokudo Munehiro Nakata Wei Tang

出版者

バイオ&ソーシャル・サイエンス推進国際研究交流会

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.7, no.1, pp.1-8, 2013-02-28 (Released:2014-06-13)

参考文献数

75

被引用文献数

8 28

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ABSTRACT: Numerous studies have documented that in cancer therapy flavonoids extracted from traditional Chinese medicine have anti-tumor activity or can enhance efficiency of chemotherapy in combination with chemotherapeutics. Thus, an awareness of flavonoids is needed by physicians and medical researchers. This review provides evidence about anti-hepatocellular carcinoma activity of flavonoids. First, as a common employed in vitro model, profile of HepG2 is shown. Second, the intracellular signaling pathways induced by flavonoids which inhibit the HepG2 cell line are summarized. Third, study situation of anti-HBV/HCV activity of flavonoids is shown. Our review is aimed at providing an understanding of anti-HBV/HCV activity and anti-HCC mechanisms of flavonoids, and an outlook on flavonoids application on cancer therapy.