Hiroshi Koyama

Gunma University, Maebashi, Gunma, Japan

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Publications (70)97.27 Total impact

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    ABSTRACT: During a previous study that aimed to identify anticancer agents within primate‑consumed plants, the present group identified that Eugenia aquea (E. aquea) possessed potential as a source of anticancer agents. The ethanol extract of E. aquea leaves exhibited strong inhibitory activity against the proliferation of the human breast adenocarcinoma MCF‑7 cell line. The inhibition of proliferation was determined using an MTT assay. The present study was performed to isolate the active compound within the E. aquea leaves that generated the aforementioned activity, and resulted in the isolation of 2',4'‑dihydroxy‑6‑methoxy‑3,5‑dimethylchalcone, which was identified through the analysis of spectroscopic data. This compound was examined for its inhibitory activity against the MCF‑7 cell line using a MTT assay, and the ability of 2',4'‑dihydroxy‑6‑methoxy‑3,5‑dimethylchalcone to induce apoptosis through the activation of the poly(adenosine diphosphate‑ribose) polymerase (PARP) protein was also investigated. The results of the present study revealed that the isolated compound inhibited cell proliferation in a dose‑dependent manner, possessed an IC50 of 74.5 μg/ml (250 μM) and promoted apoptosis via the activation of PARP. It was concluded that these results indicated a requirement for additional investigations into 2',4'‑dihydroxy‑6‑methoxy‑3,5‑dimethylchalcone in order to provide a basis for the use of this compound in the management of cancer.
    Oncology letters 05/2015; 9(5):2303-2306. DOI:10.3892/ol.2015.2981 · 1.55 Impact Factor
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    ABSTRACT: Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36−/− mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36−/− mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue 125I-BMIPP and the glucose analogue 18F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36−/− mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36−/− mice after cold exposure. These findings strongly suggest that CD36−/− mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation.
    Biochemical and Biophysical Research Communications 01/2015; 457(4). DOI:10.1016/j.bbrc.2014.12.124 · 2.30 Impact Factor
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    ABSTRACT: Prostate cancer has become a leading cause of mortality in humans. Previous studies have shown the potential anticancer properties of kaempferol‑3‑O‑rhamnoside in breast cancer cell lines. In the present study, the anticancer potential of kaempferol‑3‑O‑rhamnoside was investigated in LNCaP human prostate cancer cell lines. The inhibition of cell proliferation was investigated using MTT assays, whereas its ability to induce the caspase‑cascade pathway was investigated by western blotting. The results showed that kaempferol‑3‑O‑rhamnoside inhibits the proliferation of LNCaP cells in a dose‑dependent manner by upregulating the expression of caspase‑8, caspase‑9, caspase‑3 and poly (ADP‑ribose) polymerase proteins. Although further studies are required, the results of the present study indicate the potential application of kaempferol‑3‑O‑rhamnoside in cancer treatment.
    01/2015; 3(1):115-117. DOI:10.3892/br.2014.385
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    ABSTRACT: The effects of selenium on pre β-HDL formation were observed in a human primary hepatocyte (Hc cells) under a basal state condition, to represent the human liver in healthy conditions. The Hc cells were cultured in a medium supplemented with 0-10 μM sodium selenite. The effects of sodium selenite supplementation on several target proteins and genes related to pre β-HDL formation were measured by western blot analysis and real-time PCR, respectively. Protein expressions of GPx-1 and apolipoprotein A-I (apo A-I) were upregulated after treatment with sodium selenite. These results were confirmed by increased mRNA expressions of these two genes. The optimum effects of sodium selenite supplementation on protein and mRNA expressions of apoA-I and GPx-1 occurred at 50 nM; however, higher concentrations reduced the effect. In contrast, the expression levels of other pre β-HDL formation-related proteins and mRNA, apolipoprotein A-II (apo A-II) and ATP-binding cassette transporter-1 (ABCA-1), were not significantly affected. These results suggest that sodium selenite supplementation might play a role in pre β-HDL formation in Hc cells under basal state at low doses but not at high doses. Thus, an appropriate dose of selenium supplementation is essential for achieving the therapeutic potential of selenium supplementation for preventing CVD events in healthy individuals.
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    ABSTRACT: A 90-day randomized, double-blind, placebo-controlled, pre-post trial was conducted in four groups of Indonesian children aged 12–24 months: placebo, probiotic, zinc, and a combination of probiotic and zinc (n = 12 per group). Microencapsulated Lactobacillus plantarum IS-10506 of dadih origin was supplemented at a dose of 1010CFU/day as a probiotic. Zinc was supplemented as 20 mg zinc sulfate monohydrate (8 mg zinc elemental). Blood and stool samples were collected at baseline and at the endof the study period. Fecal sIgA was assessed by ELISA and serum zinc concentrations by ICP-MS. Fecal sIgA increased significantly in the probiotic group (30.33 ± 3.32 μg/g; p < 0.01) and in the combination probiotic and zinc group (27.55 ± 2.28 μg/g; p < 0.027), as compared with the placebo group (13.58 ± 2.26 μg/g). Changes in serum zinc concentrations in the combination probiotic and zinc group showed the highest elevation at the end of the study period. A combination of probiotic L. plantarum IS-10506 at a dose of 1010CFU/day and 8 mg of elemental zinc supplementation showed a potential ability to improve the zinc status of pre-school children. Taken together, supplementation with the probiotic L. plantarum IS-10506 and zinc for 90 days resulted in a significantly increased humoral immune response, as well as improved zinc status, in young children.
    Journal of Trace Elements in Medicine and Biology 10/2014; 28(4). DOI:10.1016/j.jtemb.2014.07.009 · 2.37 Impact Factor
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    ABSTRACT: Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate?consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 µg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine?resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 µg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 µg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC50 of 106 µM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.
    07/2014; 2(4):579-583. DOI:10.3892/br.2014.271
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    ABSTRACT: To establish guidelines for the selenium supplementation in radiotherapy we assessed the benefits and risks of selenium supplementation in radiotherapy. Clinical studies on the use of selenium in radiotherapy were searched in the PubMed electronic database in January 2013. Sixteen clinical studies were identified among the 167 articles selected in the initial search. Ten articles were observational studies, and the other 6 articles reported studies on the effects of selenium supplementation in patients with cancer who underwent radiotherapy. The studies were conducted worldwide including European, American and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium levels were common parameters used to assess the effects of radiotherapy and the selenium supplementation status. Selenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200-500 mug/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of selenium supplementation.
    Radiation Oncology 05/2014; 9(1):125. DOI:10.1186/1748-717X-9-125 · 2.55 Impact Factor
  • Obesity Research & Clinical Practice 10/2013; 7. DOI:10.1016/j.orcp.2013.08.078 · 1.18 Impact Factor
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    ABSTRACT: Selenium is an essential nutrient for human health, and maternal selenium concentration has been reported to be associated with pregnancy outcome. To further investigate the possible role of selenium (Se) in miscarriage, we conducted a case-control study to evaluate the correlations among selenium status, glutathione peroxidase activity, and spontaneous abortion. A total of 46 subjects with normal pregnancies and 25 subjects with spontaneous abortion were recruited, and their serum selenium concentrations and serum glutathione peroxidase activities were analyzed. The total serum selenium concentrations in subjects with normal pregnancies were significantly higher than those of subjects with spontaneous abortion; however, the glutathione peroxidase activities were similar in both groups. We further separated the subjects into smoking and nonsmoking groups, and the logistic regression analysis suggested that total serum selenium concentration, but not serum glutathione peroxidase activity or smoking, was significantly correlated with the incidence of miscarriage. The present study thus reaffirms that low serum selenium levels are associated with miscarriage and that selenium plays an important role in pregnancy maintenance.
    Biological trace element research 05/2013; 154(1). DOI:10.1007/s12011-013-9701-0 · 1.75 Impact Factor
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    ABSTRACT: Background & Aims: This study examined the effects of education, occupation, social networks and psychological factors on all-cause mortality in a middle-aged Japanese cohort. Methods: The cohort study (n: 11,565) was conducted from 1993 until 2011. The subjects were middle-aged males and females living in rural (n: 4,501; deaths: 669) and urban (n: 7,064; deaths: 1,190) areas in Gunma, Japan. Cox proportional hazards model was applied to investigate how various factors affect mortality risk. Results: In the age-adjusted model, higher educated rural males had significantly lower risks (junior high school: 1.00; high school: 0.76; junior college: 0.57), though rural females had a U-shaped risk pattern with the lowest significant risk (0.63) in the high school group. Also, males who were non-married or non-participated or heavily drinking or never exercised or BMI less than 18.5 or having chronic diseases or depression had significantly higher mortality risks. Current smoking was only one universal factor that was still significantly affected increased risk of mortality across both areas and genders. Conclusions: In the rural area, educational levels were related to mortality risk, but the risk patterns were different from genders. Males of poorer social networks had higher mortality risks.
    The Kitakanto Medical Journal 03/2013; 63(1):21-32. DOI:10.2974/kmj.63.21
  • Hiroshi Koyama · Mutakin · Rizky Abdulah · Chiho Yamazaki · Satomi Kameo
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    ABSTRACT: The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 μg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2013; 68(1):1-10. DOI:10.1265/jjh.68.1
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    ABSTRACT: Background and aim: Previous evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity. Methods: Plasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n=78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group. Results: In the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r=0.390, P<0.05) and with fatty acid binding protein-4 (FABP4) (r=0.474, P<0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r=-467, P<0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r=0.413, P<0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r=-0.429, P<0.05). Conclusions: These results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.
    Journal of Trace Elements in Medicine and Biology 11/2012; 27(2). DOI:10.1016/j.jtemb.2012.09.006 · 2.37 Impact Factor
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    ABSTRACT: Primate-consumed plants are assumed to be a promising source of therapeutic agents since primates can survive and be cured from any disease by their daily consumed food. In the course of our study to search for anticancer agents, we evaluated 42 species of plants usually consumed by primates for their antiproliferative activity against cell lines of human breast adenocarcinoma (MCF-7). In this study, crude ethanol extracts of the plants were tested using MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay. The results showed that four extracts of Dysoxylum caulostachyum, Eugenia aquea, Garcinia celebica, and Psychotria valentonic leaves strongly inhibited the MCF-7 cell proliferation with IC50 values of 12, 58, 87, and 87 μg/ml, respectively. Further examination on the fractions of the four extracts indicated that the ethyl acetate fraction of D. caulostachyum, the n-hexane fractions of E. aquea and G. celebica, and the water fraction of P. valentonic were the most active fractions with the IC50 of 78 , 24, 60, and 23 μg/ml, respectively. These results suggest that primate-consumed plants might have potential as a source of anticancer agents.
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    ABSTRACT: Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.
    Oncology letters 05/2012; 3(5):1069-1072. DOI:10.3892/ol.2012.596 · 1.55 Impact Factor
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  • The Kitakanto Medical Journal 01/2012; 62(1):41-51. DOI:10.2974/kmj.62.41
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    ABSTRACT: SUMMARYPlasmodium falciparum has for some time been developing resistance against known anti-malarial drugs, and therefore a new drug is urgently needed. Selenium (Se), an essential trace element, in the form of inorganic Se, selenite (SeO32-), has been reported to have an anti-plasmodial effect, but its mechanism is still unclear. In the present study, we evaluated the anti-plasmodial effect of several Se compounds against P. falciparum in vitro. The anti-plasmodial effect of several Se compounds was analysed and their apoptosis-inducing activity was evaluated by morphological observation, DNA fragmentation assay and mitochondrial function analysis. SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial effects with 50% inhibition concentration at 9, 10, 45, and 65 μm, respectively, while selenate and methylselenocysteine up to 100 μm have no effect on parasite growth. The effective Se compounds caused the parasites to become shrunken and pyknotic and significantly increased mitochondrial damage against P. falciparum compared to the untreated control. In conclusion, SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial activities that induce apoptosis-like cell death in P. falciparum, and the anti-plasmodial effects of Se seem to be based on its chemical forms. The apoptosis-like cell-death mechanism in P. falciparum can be beneficial to respond to the growing problem of drug resistance.
    Parasitology 08/2011; 138(14):1-11. DOI:10.1017/S0031182011001399 · 2.56 Impact Factor
  • Rizky Abdulah · Kenji Kobayashi · Chiho Yamazaki · Hiroshi Koyama
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    ABSTRACT: Prostate cancer is one of the leading causes of cancer-related deaths among males. Although use of the micro-nutrient selenium in prostate cancer clinical trials is limited, the outcomes indicate that selenium is a promising treatment. Furthermore, selenium inhibits prostate cancer through multiple mechanisms, and it is beneficial in controlling the development of this disease. This review highlights the latest epidemiological and biomolecular research on selenium in prostate cancer, as well as its prospects for future clinical use.
    International Journal of Oncology 08/2011; 39(2):301-9. DOI:10.3892/ijo.2011.1035 · 3.03 Impact Factor
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    ABSTRACT: Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p < 0.05) and decreases in the plasma Se concentration (p < 0.05) and in serum albumin (p < 0.05) after surgery were observed. Since albumin is a Se-containing protein and represents a negative acute phase protein that provides amino acids for the production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.
    Biological trace element research 06/2011; 144(1-3):388-95. DOI:10.1007/s12011-011-9107-9 · 1.75 Impact Factor
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    ABSTRACT: Depression is a common mental disorder. Several studies suggest that lifestyle and health status are associated with depression. However, only a few large-scale longitudinal studies have been conducted on this topic. The subjects were middle-aged and elderly Japanese adults between the ages of 40 and 69 years. A total of 9,650 respondents completed questionnaires for the baseline survey and participated in the second wave of the survey, which was conducted 7 years later. We excluded those who complained of depressive symptoms in the baseline survey and analyzed data for the remaining 9,201 individuals. In the second-wave survey, the DSM-12D was used to determine depression. We examined the risks associated with health status and lifestyle factors in the baseline survey using a logistic regression model. An age-adjusted analysis showed an increased risk of depression in those who had poor perceived health and chronic diseases in both sexes. In men, those who were physically inactive also had an increased risk of depression. In women, the analysis also showed an increased risk of depression those with a BMI of 25 or more, in those sleeping 9 hours a day or more and who were current smokers. A multivariate analysis showed that increased risks of depression still existed in men who had chronic diseases and who were physically inactive, and in women who had poor perceived health and who had a BMI of 25 or more. These results suggest that lifestyle and health status are risk factors for depression. Having a chronic disease and physical inactivity were distinctive risk factors for depression in men. On the other hand, poor perceived health and a BMI of 25 or more were distinctive risk factors for depression in women. Preventive measures for depression must therefore take gender into account.
    BMC Psychiatry 02/2011; 11(20):20. DOI:10.1186/1471-244X-11-20 · 2.21 Impact Factor

Publication Stats

574 Citations
97.27 Total Impact Points


  • 1987–2014
    • Gunma University
      • Department of Public Health
      Maebashi, Gunma, Japan
  • 2007
    • Tokyo University and Graduate School of Social Welfare
      Edo, Tōkyō, Japan
  • 2004
    • Jobu University
  • 2002
    • Hokuriku University
      Kanazawa, Ishikawa, Japan
  • 2000
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 1998
    • Tohoku University
      • Department of Environmental Bioscience
      Sendai, Kagoshima, Japan