著者

Hyun-Kyung Chang Mal-Soon Shin Hye-Young Yang Jin-Woo Lee Young-Sick Kim Myoung-Hwa Lee Jullia Kim Khae-Hawn Kim Chang-Ju Kim

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.8, pp.1597-1602, 2006 (Released:2006-08-01)

参考文献数

41

被引用文献数

83 144

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Prostate cancer is one of the most common non-skin cancers in men. Amygdalin is one of the nitrilosides, natural cyanide-containing substances abundant in the seeds of plants of the prunasin family that have been used to treat cancers and relieve pain. In particular, D-amygdalin (D-mandelonitrile-β-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. Apoptosis, programmed cell death, is an important mechanism in cancer treatment. In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells. In the present results, DU145 and LNCaP cells treated with amygdalin exhibited several morphological characteristics of apoptosis. Treatment with amygdalin increased expression of Bax, a pro-apoptotic protein, decreased expression of Bcl-2, an anti-apoptotic protein, and increased caspase-3 enzyme activity in DU145 and LNCaP prostate cancer cells. Here, we have shown that amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. The present study reveals that amygdalin may offer a valuable option for the treatment of prostate cancers.

著者

Harumi Okuyama Yoichi Fujii Atsushi Ikemoto

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.46, no.3, pp.157-177, 2000-06-01 (Released:2008-04-14)

参考文献数

183

被引用文献数

16 27

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Classic lipid nutrition for the prevention of chronic, elderly-onset diseases was apparently established before 1960, assuming that hypercholesterolemia is the major risk factor and that raising the polyunsaturated/saturated (P/S) ratio of dietary fatty acids is hypocholesterolemic. However, the hypocholesterolemic effect of linoleic acid (LA) was found to be transient. Furthermore, hypercholesterolemia itself is unlikely to be a serious risk factor for diseases in the elderly because serum cholesterol level is positively correlated with longevity. Instead, a high n-6/n-3 ratio of dietary fatty acids was found to increase thrombotic tendency, decrease peripheral blood flow and lead to persistent inflammation, which was proposed to be the major risk factor for atherosclerosis and related diseases. Based on animal experiments and epidemiological studies, we recommend a reduction in the intake of LA from a current value of >6 en% to half, and a reduced n-6/n-3 ratio from the current value of >4 to 2. Simply decreasing LA intake would produce the recommended n-6 and n-3 fatty acid balance in Japan due to the typical Japanese diet, but both decreasing the intake of LA and increasing that of n-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is necessary in Western industrialized countries for the effective prevention of atherosclerosis and related diseases, as well as of apoplexy, allergic hyper-reactivity and cancers typical in Western populations.

著者

藤田 貢 洪 卿秀 伊東 八重 三沢 悟 竹内 尚人 仮家 公夫 西室 悟司

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.9, pp.1194-1196, 1995-09-15 (Released:2008-04-10)

参考文献数

11

被引用文献数

47 72

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Intraduodenal administration of nattokinase (NK) at a dose of 80mg/kg, resulted in the degradation of fibrinogen in plasma suggesting transport of NK across the intestinal tract in normal rats. The action of NK on the cleavage of fibrinogen in the plasma from blood samples drawn at intervals after intraduodenal administration of the enzyme was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis with an anti-fibrinogen γ chain antibody. The 270 kDa fragment carrying antigenic sites for the binding of the anti-fibrinogen γ chain antibody appeared within 0.5h and was then degraded gradually to a 105kDa fragment via a 200 kDa fragment. This suggests that fibrinogen was degraded to a 105 kDa fragment via several intermediates (270 and 200kDa). In parallel with the degradation process, plasma recalcification times were remarkably prolonged. NK was also detected in the plasma from blood samples drawn 3 and 5 h after administration of the enzyme by SDS-PAGE and Western blotting analysis with an anti-NK antibody. The results indicate that NK is absorbed from the rat intestinal tract and that NK cleaves fibrinogen in plasma after intraduodenal administration of the enzyme.

著者

Hidetomo Yokoo Eiichi Yamamoto Sayaka Masada Nahoko Uchiyama Genichiro Tsuji Takashi Hakamatsuka Yosuke Demizu Ken-ichi Izutsu Yukihiro Goda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.9, pp.872-876, 2021-09-01 (Released:2021-09-01)

参考文献数

23

被引用文献数

12

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N-Nitrosodimethylamine (NDMA) is a probable human carcinogen. This study investigated the root cause of the presence of NDMA in ranitidine hydrochloride. Forced thermal degradation studies of ranitidine hydrochloride and its inherent impurities (Imps. A, B, C, D, E, F, G, H, I, J, and K) listed in the European and United States Pharmacopeias revealed that in addition to ranitidine, Imps. A, C, D, E, H, and I produce NDMA at different rates in a solid or an oily liquid state. The rate of NDMA formation from amorphous Imps. A, C, and E was 100 times higher than that from crystalline ranitidine hydrochloride under forced degradation at 110 °C for 1 h. Surprisingly, crystalline Imp. H, bearing neither the N,N-dialkyl-2-nitroethene-1,1-diamine moiety nor a dimethylamino group, also generated NDMA in the solid state, while Imp. I, as an oily liquid, favorably produced NDMA at moderate temperatures (e.g., 50 °C). Therefore, strict control of the aforementioned specific impurities in ranitidine hydrochloride during manufacturing and storage allows appropriate control of NDMA in ranitidine and its pharmaceutical products. Understanding the pathways of the stability related NDMA formation enables improved control of the pharmaceuticals to mitigate this risk.

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

58 96

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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

Toshihiko Ishizaka Sachie Okada Emi Tokuyama Junji Mukai Takahiro Uchida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.56, no.10, pp.1395-1399, 2008-10-01 (Released:2008-10-01)

参考文献数

18

被引用文献数

9 10

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The aim of the study was to suppress the bitterness and improve the palatability of pediatric prednisolone powder (PP) by the addition of simple sucrose syrup (SS) and various beverages and foods. Bitterness suppression was evaluated using the human gustatory sensory test. The suppression of the bitterness and improvement of palatability of PP by addition of SS solutions was investigated using standard taste substances: sucrose for sweetness, tartaric acid for sourness, and sodium chloride as saltiness. Dilution with SS solutions of up to 50% (w/w) was successful in bitterness-suppression and improvement of palatability, but at 80% (w/w) SS, the palatability of the diluted solution was reduced. The kinematic viscosities of SS solutions were therefore evaluated using the Uberorde viscosity meter, to see whether the high viscosity of the more concentrated solutions was responsible for the reduced palatability. The kinematic viscosity of the 80% SS was 16.60 mm2/s. Judging from above information, the palatability might become worse when the kinematic viscosity of syrup exceeded 15 mm2/s. Finally, the ability of various beverages and foods with low viscosity to suppress the bitterness and improve the palatability of PP were examined. The additions of orange juice or a carbonated lemon drink to simple syrup solution were most effective in suppressing bitterness and improving palatability of PP.

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

被引用文献数

1

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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

Maaged Akiel Jawaher Alsughayyir Ahmed M. Basudan Hassan S. Alamri Ayed Dera Tlili Barhoumi Abdullah M. Al Subayyil Yasser S. Basmaeil Fahad M. Aldakheel Raid Alakeel Hazem K. Ghneim Yazeed A. Al-Sheikh Yasser Alraey Saeed Asiri Mohammad A. Alfhili

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.3, pp.372-378, 2021-03-01 (Released:2021-03-01)

参考文献数

33

被引用文献数

12

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The prevalence of cancer-associated anemia (CIA) is high, and the mechanisms governing its development remain poorly understood. Eryptosis, the suicidal cell death of red blood cells (RBCs), may account for CIA as it is triggered by clinically approved chemotherapeutics including cisplatin and paclitaxel. Physcion (PSN), an anthraquinone extracted from rhubarb and other plants, has shown great promise as an anticancer agent. However, the potential toxicity of PSN to RBCs remains elusive. RBCs were isolated from heparinized blood, and incubated with 10–100 µM of PSN for 24 h at 37 °C. Hemolysis was photometrically calculated from hemoglobin concentration in the medium at 405 nm, while flow cytometry was employed to investigate cardinal markers of eryptosis. Phosphatidylserine (PS) exposure was detected by Annexin-V-fluorescein isothiocyanate (FITC), intracellular calcium by Fluo4/AM, cellular volume from forward scatter (FSC), and oxidative stress by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). PSN induced overt hemolysis at 50 and 100 µM which was not mediated through calcium influx, protein kinase C, casein kinase 1α, or receptor-interacting protein 1. Moreover, PSN caused significant increase in Annexin-V-FITC and Fluo4 fluorescence with no appreciable influence on FSC or DCF values. Accordingly, PSN stimulates premature eryptosis characterized by PS externalization and intracellular calcium overload without cell shrinkage or oxidative damage. In conclusion, this report shows, for the first time, that PSN is cytotoxic to RBCs by inducing hemolysis and programmed cell death which may limit its success as a chemotherapeutic agent.

著者

Yuki Asai Takumi Tashiro Yoshihiro Kondo Makoto Hayashi Hiroki Arihara Saki Omote Ena Tanio Saena Yamashita Takashi Higuchi Ei Hashimoto Momoko Yamada Hinako Tsuji Yuji Hayakawa Ryohei Suzuki Hiroya Muro Yoshiaki Yamamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.4, pp.614-620, 2023-04-01 (Released:2023-04-01)

参考文献数

33

被引用文献数

1

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Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.

著者

Noriko Saito-Tarashima Akiho Murai Noriaki Minakawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.5, pp.310-315, 2022-05-01 (Released:2022-05-01)

参考文献数

59

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DNA and RNA are ubiquitous molecules responsible for storage and transmission of genetic information and together comprise the central dogma of molecular biology. However, the recent emergence of synthetic genetic polymers is providing an opportunity to challenge the fundamental principles of life. Herein, we describe the ongoing attempts to rewrite the central dogma with 4′-thioDNA and 4′-thioRNA, which feature a sulfur instead of an oxygen atom in the furanose ring moiety. Using reconstituted Escherichia coli gene expression machinery, studies have shown that the genetic information conserved in 4′-thioDNA can be transcribed to 4′-thioRNA and eventually translated into protein, mirroring the processes that occur in nature. Such studies underscore the feasibility of controlling life by substances other than DNA and RNA.

著者

Md Mahadi Hassan Ahmed Fouad Abdelwahab Mohammed Khaled M. Elamin Hari Prasad Devkota Yoshitaka Ohno Keiichi Motoyama Taishi Higashi Teruko Imai

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.11, pp.1117-1120, 2020-11-01 (Released:2020-11-01)

参考文献数

7

被引用文献数

5

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Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity. Among 11 CyDs, sulfobutylether (SBE)-β-CyD showed the highest solubilizing effect for Zerumbone. Phase solubility diagrams of SBE-β-CyD/Zerumbone in 10% methanol solution showed AL type, and the stability constant was 756 M−1. SBE-β-CyD also formed the solid complex with Zerumbone by kneading for 90 min. Importantly, the dissolution rate of Zerumbone was improved by complexation with SBE-β- and hydroxypropyl (HP)-β-CyDs, and its supersaturation was maintained for several hours. The solubilizing effects by SBE-β-CyD was greater than that of HP-β-CyD. Moreover, SBE-β-CyD/Zerumbone complex also retained the cytotoxic activity of Zerumbone. These results suggest that CyDs, especially SBE-β-CyD, were useful to improve the solubility of Zerumbone.

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

103 150

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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

Kouichi Yoshizaki Hari Prasad Devkota Hiroharu Fujino 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.61, no.3, pp.344-350, 2013-03-01 (Released:2013-03-01)

参考文献数

24

被引用文献数

9 23

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A new dammarane-type triterpenoid saponin, chikusetsusaponin VII (1), and nineteen known triterpenoid saponins, ginsenoside Rb1 (2), ginsenoside Rb3 (3), ginsenoside Rc (4), ginsenoside Rd (5), ginsenoside Re (6), ginsenoside Rg1 (7), ginsenoside Rg2 (8), ginsenoside Rh1 (9), notoginsenoside R1 (10), notoginsenoside R2 (11), notoginsenoside Fe (12), chikusetsusaponin IVa (13), chikusetsusaponin IV (14), chikusetsusaponin V (15), chikusetsusaponin VI (16), chikusetsusaponin FK6 (17), gypenoside XVII (18), 28-desglucosylchikusetsusaponin IV (19), and zingibroside R1 (20), were isolated from rhizomes, taproots, and lateral roots of Panax japonicus C. A. Meyer, so-called “Satsuma-ninjin,” grown in southern Miyazaki Prefecture, Japan. The structure of new chikusetsusaponin VII was elucidated on the basis of spectral and physicochemical evidence. Although the chemical composition of the rhizome was found to be similar to that of the “Chikusetsu-ninjin,” the saponin composition of lateral root of “Satsuma-ninjin” was found to be close to that of lateral root of P. ginseng. The total yield of oleanolic acid saponins of the taproot was less than that of rhizome, but the total yield of dammarane-type saponins of the taproot was found to be similar to that of rhizome.

著者

Xiaolu FENG Jincai LU Hailiang XIN Lei ZHANG Yuliang WANG Kexuan TANG

出版者

The Pharmaceutical Society of Japan

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.3, pp.423-429, 2011-03-01 (Released:2011-03-01)

参考文献数

25

被引用文献数

19 32

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The aim of this study was to ascertain the anti-arthritic active fraction of Capparis spinosa L. (Capparidaceae) fruits and its chemical constituents. The adjuvant arthritic rat model was developed to evaluate the anti-arthritic effects of different fractions of ethanol extraction from C. spinosa L. The fraction eluted by ethanol-water (50:50, v/v) had the most significant anti-arthritic activity. The chemical constituents of this fraction were therefore studied; seven known compounds were isolated and identified as: (1) P-hydroxy benzoic acid; (2) 5-(hydroxymethyl) furfural; (3) bis (5-formylfurfuryl) ether; (4) daucosterol; (5) α-D-fructofuranosides methyl; (6) uracil; and (7) stachydrine.

著者

Yujiro Kameyama Maki Matsuhama Chie Mizumaru Rieko Saito Tsuyoshi Ando Seiko Miyazaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.12, pp.1301-1313, 2019-12-01 (Released:2019-12-01)

参考文献数

60

被引用文献数

13

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A pharmacopoeia’s core mission is to protect public health by creating and making available public standards to help ensure the quality of drugs. In recent years, pharmacopoeias around the world have harmonized their standards in the present context of globalized drug supply chains and markets. For example, the Pharmacopoeial Discussion Group has worked to harmonize excipient monographs and general chapters. In addition, the International Meeting of World Pharmacopoeias has been held by the WHO to discuss information exchange and international collaboration, among other topics. To contribute further to the protection of public health in the globalized drug market, we conducted a comparative study of the pharmacopoeias in Japan, Europe, and the United States. We aimed to examine current differences among the Japanese Pharmacopoeia, the European Pharmacopoeia, and the United States Pharmacopeia–National Formulary and to identify areas that require further collaboration among the three pharmacopoeias. In this study, we analyzed monographs and general chapters listed in the three pharmacopoeias. We identified the features of the monographs and general chapters listed in each pharmacopoeia, as well as differences across the pharmacopoeias. Moreover, on the basis of our findings, we suggest standards that require further collaboration among the pharmacopoeias in certain preferred areas. The comparison data produced by this study are expected to be used to develop strategies for future revisions of pharmacopoeias around the world.

著者

Masafumi Noda Narandalai Danshiitsoodol Takemasa Sakaguchi Keishi Kanno Masanori Sugiyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.12, pp.1886-1890, 2021-12-01 (Released:2021-12-01)

参考文献数

39

被引用文献数

8

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A lactic acid bacterial strain, Lactobacillus plantarum SN35N, which has been isolated from the pear, secretes negatively charged acidic exopolysaccharide (EPS) to outside cells. We have previously found that the SN35N-derived acidic EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.35) promoting inflammation. The aim of this study is to find other health benefits of EPS. EPS has been found to exhibit an inhibitory effect against the influenza virus (Alphainfluenzavirus Influenza A virus) and feline calicivirus (Vesivirus Feline calicivirus), which is recognized as a model of norovirus. Although more studies on the structure–function relationship of EPSs are needed, SN35N-derived EPS is a promising lead for developing not only anti-inflammatory agents, but also antiviral substances.

著者

Yisa Han Tongtong Lan Xuezhen Ma Ning Yang Chuhui Wang Zhen Xu Zhao Chen Meng Tao Hui Li Haitao Wang Yang Song

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.8, pp.1145-1151, 2023-08-01 (Released:2023-08-01)

参考文献数

48

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Inositol hexaphosphate (IP6), a widely found natural bioactive substance in grains, effectively inhibits the progression of colorectal cancer (CRC) when used in combination with inositol (INS). We previously showed that supplementation of IP6 and INS upregulated the claudin 7 gene in orthotropic CRC xenografts in mice. The aim of this study was to elucidate the role of claudin 7 in the inhibition of CRC metastasis by IP6 and INS, and explore the underlying mechanisms. We found that IP6, INS and their combination inhibited the epithelial–mesenchymal transition (EMT) of colon cancer cell lines (SW480 and SW620), as indicated by upregulation of claudin 7 and E-cadherin, and downregulation of N-cadherin. The effect of IP6 and INS was stronger compared to either agent alone (combination index < 1). Furthermore, the silencing of the claudin 7 gene diminished the anti-metastatic effects of IP6 and INS on SW480 and SW620 cells. Consistent with in vitro findings, the combination of IP6 and INS suppressed CRC xenograft growth in a mouse model, which was neutralized by claudin 7. Taken together, the combination of IP6 and INS can inhibit CRC metastasis by blocking EMT of tumor cells through upregulation of claudin 7.

著者

Eriko Uchida Yoshitaka Kondo Akiko Amano Shingo Aizawa Takayuki Hanamura Hitoshi Aoki Kenichi Nagamine Takeshi Koizumi Naoki Maruyama Akihito Ishigami

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.11, pp.1744-1747, 2011-11-01 (Released:2011-11-01)

参考文献数

20

被引用文献数

7 18

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It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.

著者

Shin Nakao Keiichi Kojima Yuki Sudo

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1357-1363, 2021-10-01 (Released:2021-10-01)

参考文献数

51

被引用文献数

10

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In life science research, methods to control biological activities with stimuli such as light, heat, pressure and chemicals have been widely utilized to understand their molecular mechanisms. The knowledge obtained by those methods has built a basis for the development of medicinal products. Among those various stimuli, light has the advantage of a high spatiotemporal resolution that allows for the precise control of biological activities. Photoactive membrane protein rhodopsins from microorganisms (called microbial rhodopsins) absorb visible light and that light absorption triggers the trans–cis photoisomerization of the chromophore retinal, leading to various functions such as ion pumps, ion channels, transcriptional regulators and enzymes. In addition to their biological significance, microbial rhodopsins are widely utilized as fundamental molecular tools for optogenetics, a method to control biological activities by light. In this review, we briefly introduce the molecular basis of representative rhodopsin molecules and their applications for optogenetics. Based on those examples, we discuss the high potential of rhodopsin-based optogenetics tools for basic and clinical research in pharmaceutical sciences.

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 99

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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.