Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

Uchida, Ryota; Iwamoto, Kosuke; Nagayama, Suetada; Miyajima, Atsushi; Okamoto, Hinako; Ikuta, Naoko; Fukumi, Hiroshi; Terao, Keiji; Hirota, Takashi

doi:10.3390/ijms160510105

Cited by 17 publications

(23 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Gamma CD, widely accepted as food constituent, consists of 8 glucose monomers arranged in the form of a cyclic ring. It has been reported to enhance the bioavailability of hydrophobic ingredients such as coenzyme Q10 [52–54]. We recruited CDs for aqueous extraction of bioactives from Ashwagandha leaves.…”

Section: Resultsmentioning

confidence: 99%

Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts

Kaul

Ishida²,

Tamura³

et al. 2016

PLoS ONE

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts

Kaul

Ishida²,

Tamura³

et al. 2016

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…Then, we examined where the enantioselective absorption occurred in the gastrointestinal tract. We previously reported that RLA was rapidly absorbed from the stomach to some extent [ 41 ]. Based on this, we evaluated the absorption separately from the stomach and small intestine after administration of the racemic mixture to pylorus ligated rats.…”

Section: Discussionmentioning

confidence: 99%

“…The procedure of surgery and administration was performed as previously reported [ 41 ]. Briefly, under isoflurane anesthesia, the abdomen was opened, the pylorus was slightly lifted and ligated with cotton thread, and then the incision was closed immediately with suture and an adhesive was applied.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Uchida

Okamoto

Ikuta

et al. 2015

IJMS

Self Cite

View full text Add to dashboard Cite

α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance.

show abstract

“…γCD, widely accepted for use in food, pharmaceutical, agricultural and chemical industry constitutes of 8 glucose monomers arranged in the form of a cyclic ring. It has been reported to enhance the bioavailability of hydrophobic ingredients such as coenzyme Q10 42 - 44 .…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin

Wadhwa¹,

Nigam²,

Bhargava³

et al. 2016

J. Cancer

Self Cite

View full text Add to dashboard Cite

Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for a variety of health promoting and therapeutic potentials. We investigated the molecular mechanism of anticancer and anti-metastasis activities of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells revealed activation of DNA damage signaling involving upregulation of GADD45α and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE is capable of disrupting mortalin-p53 complexes. We provide experimental evidence and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to nuclear translocation and activation of p53 resulting in growth arrest in cancer cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and several other key regulators of cell migration accountable for its anti-metastasis activity. Of note, we found that whereas CAPE was unstable in the culture medium (as it gets degraded into caffeic acid by secreted esterases), its complex with gamma cyclodextrin (γCD) showed high efficacy in anti-tumor and anti-metastasis assays in vitro and in vivo (when administered through either intraperitoneal or oral route). The data proposes that CAPE-γCD complex is a potent anti-cancer and anti-metastasis reagent.

show abstract

Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

Cited by 17 publications

References 44 publications

Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts

Novel Methods to Generate Active Ingredients-Enriched Ashwagandha Leaves and Extracts

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin

Contact Info

Product

Resources

About