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Wadhwa R.,Japan National Institute of Advanced Industrial Science and Technology | Singh R.,Japan National Institute of Advanced Industrial Science and Technology | Gao R.,Japan National Institute of Advanced Industrial Science and Technology | Shah N.,Japan National Institute of Advanced Industrial Science and Technology | And 6 more authors.
PLoS ONE | Year: 2013

Background:Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX).Methodology/Principal Findings:Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected.Conclusion:We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine. © 2013 Wadhwa et al. Source


Kashima N.,Osaka City University | Fujikura Y.,Osaka City University | Komura T.,Osaka City University | Fujiwara S.,Osaka City University | And 3 more authors.
Biogerontology | Year: 2012

Methods for quantitative oral administration of various substances to Caenorhabditis elegans are needed. Previously, we succeeded in oral administration of hydrophilic substances using liposomes. However, an adequate system for delivery of hydrophobic chemicals was not available. In this study, we developed a method for oral administration of lipidsoluble substances to C. elegans. γ-cyclodextrin (γCD), which delivers hydrophobic chemicals, was used to make micro-particles of inclusion compounds that can be ingested by bacteriophagous nematodes, which do not distinguish these micro-particles from their food bacteria. Successful oral delivery of the hydrophobic fluorescent reagent 3,3′-dioctadecyloxacarbocyanine perchlorate into the intestines of C. elegans was observed. Oral administration of the hydrophobic antioxidants tocotrienol, astaxanthin, or c-tocopherol, prolonged the nematode lifespan; tocotrienol rendered them resistant to infection with the opportunistic pathogen Legionella pneumophila. In contrast, older conventional delivery methods that involve incorporation of chemicals into the nematode growth medium or pouring chemicals onto the plate produced weaker fluorescence and no longevity effects. Our method efficiently and quantitatively delivers hydrophobic solutes to nematodes, and a minimum effective dose was estimated. In combination with our liposome method, this γCD method expands the usefulness of C. elegans for the discovery of functional food factors and for screening drug candidates. © 2012 Springer Science+Business Media B.V. Source


Yaguchi Y.,Osaka City University | Komura T.,Osaka City University | Kashima N.,Osaka City University | Tamura M.,Osaka City University | And 4 more authors.
European Journal of Nutrition | Year: 2014

Results: Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1.Conclusions: Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).Purpose: Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans.Methods: Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects. © 2014, Springer-Verlag Berlin Heidelberg. Source


Furuishi T.,Hoshi University | Ishigami T.,Hoshi University | Endo T.,Hoshi University | Nagase H.,Hoshi University | And 3 more authors.
Pharmazie | Year: 2015

Actinidin (ATD) is a cysteine protease found in kiwifruit. It is used to tenderize meat and to enhance the digestion of proteins in the small intestine. However, ATD is unstable during freeze-drying, which alters its bioactivity. It is well known that sugars have the ability to protect proteins from the stress of freezedrying. In this study, we investigated the protective effect of various saccharides on the stability of ATD during freeze-drying. The ATD activities of the samples containing γ-cyclodextrin (CyD) showed only a small decrease, and compared with trehalose and sucrose, γ-CyD was a more effective stabilizer for ATD. Secondary structural changes in freeze-dried ATD were observed by circular dichroism spectroscopy and compared with the changes in stabilized samples. There was a close relationship between the α-helix content and the stabilization. The sugars stabilized the protein by suppressing the changes in the α-helix. Fourier transform infrared spectroscopy measurement showed that the amide I band of ATD with γ-CyD was shifted to a lower wavenumber compared with other sugars. Therefore, stronger hydrogen bonds may be formed between ATD and γ-CyD than between ATD and other sugars. The suppression of changes in the protein secondary structure accompanying the formation of hydrogen bonding between the protein and the sugar also contributed to the protective effect of the sugars. Source


Hirogaki K.,Industrial Research Institute of Ishikawa | Kamitani J.,Industrial Research Institute of Ishikawa | Kimizu M.,Industrial Research Institute of Ishikawa | Yamamoto T.,Industrial Research Institute of Ishikawa | And 8 more authors.
Sen'i Gakkaishi | Year: 2010

Inclusion complex of cyclodextrin (CD) with vitamin E (VE) or iodine was fixed onto a fabric using water based polyisocyanate as a crosslinker, and their durability and anti-oxidant activity or bactericidal activity were discussed. γ-CD complex was used for VE and α-, β-, or methylated β-CD complex were used for iodine. The poly (ethylene terephthalate) fabric was dipped into a suspension of a complex and polyisocyanate, and the fabric was cured to prepare a network of the complex and polyisocyanate. When a complex was fixed on the fabric with empty CD of its same kind showed higher fixed rate of VE or iodine. The fabric showed higher durability when a complex was fixed using treating solution with lower ratio of a complex and higher ratio of a catalyst on polyisocyanate at higher curing temperature. For the fabric with the highest durability, 20 % of VE remained on the fabric even after 50-times wash. Anti-oxidant activity of the fabric was evaluated from the quenching of 2,2-diphenyl-l-picrylhydrazyl radical. The iodine-fixed fabric showed bactericidal activity after 10-times wash, which came up to the anti-bacterial standard of textile for general-use (orange ravel) of Japan Textile Evaluation Technology Council (SEK). Source

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