CycloChem Co.

Chūō-ku, Japan

CycloChem Co.

Chūō-ku, Japan

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Nakatani Y.,Osaka City University | Yaguchi Y.,Osaka City University | Komura T.,Osaka City University | Nakadai M.,Osaka City University | And 3 more authors.
European Journal of Nutrition | Year: 2017

Purpose: Sesamin, a polyphenolic compound found in sesame seeds, has been reported to exert a variety of beneficial health effects. We have previously reported that sesamin increases the lifespan of Caenorhabditis elegans. In this study, we investigated the molecular mechanisms underlying the longevity effect of sesamin in C. elegans. Methods: Starting from three days of age, Caenorhabditis elegans animals were fed a standard diet alone or supplemented with sesamin. A C. elegans genome array was used to perform a comprehensive expression analysis. Genes that showed differential expression were validated using real-time PCR. Mutant or RNAi-treated animals were fed sesamin, and the lifespan was determined to identify the genes involved in the longevity effects of sesamin. Results: The microarray analysis revealed that endoplasmic reticulum unfolded protein response-related genes, which have been reported to show decreased expression under conditions of SIR-2.1/Sirtuin 1 (SIRT1) overexpression, were downregulated in animals supplemented with sesamin. Sesamin failed to extend the lifespan of sir-2.1 knockdown animals and of sir-2.1 loss-of-function mutants. Sesamin was also ineffective in bec-1 RNAi-treated animals; bec-1 is a key regulator of autophagy, and is necessary for longevity induced by sir-2.1 overexpression. Furthermore, the heterozygotic mutation of daf-15, which encodes the target of rapamycin (TOR)-binding partner Raptor, abolished lifespan extension by sesamin. Moreover, sesamin did not prolong the lifespan of loss-of-function mutants of aak-2, which encodes the AMP-activated protein kinase (AMPK). Conclusions: Sesamin extends the lifespan of C. elegans through several dietary restriction-related signaling pathways, including processes requiring SIRT1, TOR, and AMPK. © 2017 Springer-Verlag Berlin Heidelberg


Terao K.,Cyclochem Co. | Nakata D.,Cyclochem Co. | Jo A.,Cyclochem Co. | Urano A.,Cyclochem Co. | And 6 more authors.
Journal of Inclusion Phenomena and Macrocyclic Chemistry | Year: 2014

In the present study investigated the effect of curcumin (CUR) alpha (α), beta (β) and gamma (γ) cyclodextrin (CD) complexes on its solubility and bioavailability. CUR the active principle of turmeric is a natural antioxidant agent with potent anti-inflammatory activity along with chemotherapeutic and chemopreventive properties. Poor solubility and poor oral bioavailability are the main reasons which preclude CUR use in therapy. Extent of complexation was β-CD complex (82 %) > γ-CD (71 %) > α-CD (65 %). Pulverization method resulted in significant enhancement of CUR (0.002 mg/ml) solubility with CUR α-CD complex (0.364 mg/ml) > CUR β-CD complex (0.186 mg/ml) > CUR γ-CD complex (0.068 mg/ml). Gibbs-free energy and in silico molecular docking studies favour formation of α-CD complex > β-CD complex > γ-CD complex. With reference to CUR, relative bioavailability of CUR α-CD, CUR β-CD and CUR γ-CD complexes were 460, 365 and 99 % respectively. CUR-CD complexes exhibited increased bioavailability with an increase in t/, tmax, Cmax, AUC, Ka, and MRT; and a decrease in Ke, clearance and Vd values. AUC increase was CUR α-CD complex > CUR β-CD complex > CUR γ-CD complex. Significant difference (p < 0.05) was observed between CUR α-CD complex and CUR γ-CD complex by one-way ANOVA and Dunnett's post hoc test for multiple comparison analysis. Correlation observed between in vitro, in vivo and in silico methods indicates potential of in silico and in vitro methods in CD selection. © 2013 Springer Science+Business Media Dordrecht.


Ikeda S.,Nagoya University of Arts and Sciences | Uchida T.,Nagoya University of Arts and Sciences | Ichikawa T.,Nagoya University of Arts and Sciences | Watanabe T.,Oryza Oil and Fat Chemical Co. | And 4 more authors.
Bioscience, Biotechnology and Biochemistry | Year: 2010

To determine the bioavailability of tocotrienol complex with γ-cyclodextrin, the effects of tocotrienol/γ-cyclodextrin complex on tocotrienol concentration in rat plasma and tissues were studied. Rats were administered by oral gavage an emulsion containing tocotrienol, tocotrienol with γ-cyclodextrin, or tocotrienol/γ-cyclodextrin complex. At 3h after administration, the plasma γ-tocotrienol concentration of the rats administered tocotrienol/γ-cyclodextrin complex was higher than that of the rats administered tocotrienol and γ-cyclodextrin. In order to determine the effect of complexation on tocotrienol absorption, rats were injected with Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoprotein by lipoprotein lipase, and then administered by oral gavage an emulsion containing tocotrienol, tocotrienol with γ-cyclodextrin, or tocotrienol/γ-cyclodextrin complex. The plasma γ-tocotrienol concentration of the Triton-treated rats administered tocotrienol/γ-cyclodextrin complex was higher than that of the other Triton-treated rats. These results suggest that complexation of tocotrienol with γ-cyclodextrin elevates plasma and tissue tocotrienol concentrations by enhancing intestinal absorption.


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.


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.


Uekaji Y.,CycloChem Co. | Jo A.,CycloChem Co. | Ohnishi M.,CycloChem Co. | Nakata D.,CycloChem Co. | Terao K.,CycloChem Co.
Procedia Engineering | Year: 2012

We previously reported the bioavailability enhancement of lipophilic Coenzyme Q10 (CoQ10) by complexing with γ- Cyclodextrin (γCD). Here, we report on its mechanism. Hydrophobic CoQ10 generally agglutinates but the dissociated CoQ10 from γCD was captured by bile acid to form nanometer molecular micelle without aggregation and therefore both solubility and bioavailability could be enhanced. Furthermore, we succeeded in the expansion of this finding to personal care field by the use of Dipotassium glycyrrhizate (GZK2) instead of bile acid. The skin absorptions of actives could be significantly enhanced by the combination of cosme-ceutical-γCD complexes with GZK2. © 2012 Published by Elsevier Ltd.


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.


Ikeda H.,Tokyo Institute of Technology | Ikuta N.,CycloChem Co. | Nakata D.,CycloChem Co. | Fukumi H.,CycloChem Co. | Terao K.,CycloChem Co.
Journal of Inclusion Phenomena and Macrocyclic Chemistry | Year: 2012

A 1H NMR study that explored the ability of α-cyclodextrin (α-CD) to preferentially bind (R)-α-lipoic acid is presented. The interaction between α-CD and (R)-α-lipoic acid was found to be stronger than that between α-CD and (S)-α-lipoic acid. Structures for the (R)-α-lipoic acid/α-CD and (S)-α-lipoic acid/α-CD inclusion complexes were constructed using restraints derived from ROESY spectra and MM2 molecular mechanics calculations. The models built for both complexes have the 1,2-dithiolane ring and the carboxyl moiety of α-lipoic acid oriented toward the secondary and primary hydroxy sides of α-CD, respectively. © 2011 Springer Science+Business Media B.V.


PubMed | Japan National Institute of Advanced Industrial Science and Technology, DAI DAN Co., CycloChem Co., Osaka Prefecture University and Zuiron Private Ltd.
Type: Journal Article | Journal: PloS one | Year: 2016

Ashwagandha (Withania somnifera) is an Ayurvedic herb commonly used in world-renowned traditional Indian home medicine system. Roots of Ashwagandha have been traditionally known to possess a variety of therapeutic and health promoting potentials that have not been sufficiently supported by laboratory studies. Nevertheless, most, if not all, of the preventive and therapeutic potentials have been assigned to its bioactive components, steroidal alkaloids and lactones. In contrast to the traditional use of roots, we have been exploring bioactivities in leaves of Ashwagandha. Here, we report that the leaves possess higher content of active Withanolides, Withaferin-A (Wi-A) and Withanone (Wi-N), as compared to the roots. We also established, for the first time, hydroponic cultivation of Ashwagandha and investigated the effect of various cultivation conditions on the content of Wi-A and Wi-N by chemical analysis and bioassays. We report that the Withanone/Withaferin A-rich leaves could be obtained by manipulating light condition during hydroponic cultivation. Furthermore, we recruited cyclodextrins to prepare extracts with desired ratio of Wi-N and Wi-A. Hydroponically grown Ashwagandha and its extracts with high ratio of withanolides are valuable for cancer treatment.


It is an object of the present invention to provide a method for preparing a water extract of ashwagandha, which comprises increasing the amounts of withanone and withaferin A contained as active ingredients in the water extract of ashwagandha leaves. In addition, it is another object of the present invention to more economically and simply provide a pharmaceutical composition comprising ashwagandha leaves. The present invention relates to a method for preparing a water extract of ashwagandha leaves, which comprises extracting ashwagandha leaves with water in the presence of cyclodextrin, and a method for enhancing the anticancer activity of the water extract of ashwagandha leaves. The present invention also relates to a pharmaceutical composition for treating or preventing cancer, comprising the water extract of ashwagandha leaves. The present invention further relates to a pharmaceutical composition comprising dry powders of ashwagandha leaves and cyclodextrin.

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