Effect of β-Cyclodextrin Derivatives on the Diosgenin Absorption in Caco-2 Cell Monolayer and Rats

Okawara, Masaki; Tokudome, Yoshihiro; Todo, Hiroaki; Sugibayashi, Kenji; Hashimoto, Fumie

doi:10.1248/bpb.b13-00560

Cited by 24 publications

(14 citation statements)

References 19 publications

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“…Moreover, the LC-MS technique was used for bioavailability studies of diosgenin in inclusion complexes with cyclodextrins in Caco-2 cell monolayers and rat jejunum. Interestingly, bioavailability of diosgenin in the presence of β -cyclodextrin derivatives was near 4- to 11-fold higher than that of diosgenin suspension [135]. The same research group evaluated, again by using LC-MS, the effect of diosgenin liquid crystals combined with cyclodextrin to increase the bioavailability of this steroid, after oral administration to rats [136].…”

Section: Methodsmentioning

confidence: 99%

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

Jesus

Martins

Gallardo

et al. 2016

Journal of Analytical Methods in Chemistry

210

125

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Diosgenin, a steroidal sapogenin, occurs abundantly in plants such as Dioscorea alata, Smilax China, and Trigonella foenum graecum. This bioactive phytochemical not only is used as an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry, but has revealed also high potential and interest in the treatment of various types of disorders such as cancer, hypercholesterolemia, inflammation, and several types of infections. Due to its pharmacological and industrial importance, several extraction and analytical procedures have been developed and applied over the years to isolate, detect, and quantify diosgenin, not only in its natural sources and pharmaceutical compositions, but also in animal matrices for pharmacodynamic, pharmacokinetic, and toxicological studies. Within these, HPLC technique coupled to different detectors is the most commonly analytical procedure described for this compound. However, other alternative methods were also published. Thus, the present review aims to provide collective information on the most recent pharmacological data on diosgenin and on the most relevant analytical techniques used to isolate, detect, and quantify this compound as well.

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Section: Methodsmentioning

confidence: 99%

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

Jesus

Martins

Gallardo

et al. 2016

Journal of Analytical Methods in Chemistry

210

125

View full text Add to dashboard Cite

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“…The peak level of DG in the skin was observed at 6 h after oral administration. The plasma concentration of an orally administered DG reached C max (132:5 ± 48:2 ng/mL) at 5:01 ± 0:55 h with an AUC of 4121:9 ± 1354:7 ng • h/mL and an absolute oral bioavailability of 4:45 ± 1:46% [32,33]. Similarly, Liu et al have demonstrated that treatment with DG resulted in a C max of 42:1 ± 30:4 ng/mL at 11:3 ± 3:9 h along with an AUC 0-60 h of 1309:3 ± 849:8 ng h/mL and t 1/2 of 10:4 ± 4:2 h [48].…”

Section: Bioavailability and Pharmacokinetic Studies Of Diosgeninmentioning

confidence: 96%

“…However, DG is destabilized when it is exposed to hydrochloric acid [31]. DG is strongly hydrophobic (with Log P = 5:7), and it is insoluble in water [32,33]. The solubility of DG is around 0.7 ng/mL in aqueous medium [34].…”

Section: Chemistry Of Diosgeninmentioning

confidence: 99%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson’s disease, Alzheimer’s disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

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“…The aqueous solubility of DG was determined to be 0.7 ng/ml (1.69 nm). [9] It was also revealed that the low solubility of DG led to poor bioavailability and gastrointestinal mucosal toxicity. [10] As poor solubility has been recognized as a frequently encountered challenge in the field of pharmaceutics, different approaches have been employed to improve the solubility and bioavailability of poorly watersoluble compounds including DG.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Liao

Jung

et al. 2017

Chem Biol Drug Des

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Water-soluble arginyl-diosgenin (Arg-DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg-DG conjugate was characterized using FT-IR, 1 H NMR, 13 C NMR, and HPLC-MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg-DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg-DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg-DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg-DG conjugate improved the bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg-DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering. K E Y W O R D SALP assay, arginyl-diosgenin conjugate, bone tissue engineering, cytotoxicity, tube formation assay | INTRODUCTIONDiosgenin [(25R)-spirost-5-en-3ß-ol] (DG) is a major naturally occurring steroid saponin, which is abundantly distributed in the rootstock of yams (Dioscorea sp.) and other plants such as Smilax bockii warb and Trigonella foenum graecum. [1,2] DG has exhibited biological effects in the treatment of various diseases such as hypercholesterolemia, climacteric syndromes including diabetic neuropathy and even cancer. [3][4][5][6] It has also been claimed to have an osteogenic property. DG was reported to inhibit osteoclastogenesis and enhance osteoblastic cell differentiation and the synthesis of cellular bone matrix protein. [7,8] It has been hypothesized that DG could be a potential activator of bone formation and potential therapeutic agent for bone-related diseases including osteoporosis.[8]However, the medical application of DG is considerably limited because of its solubility problem and associated toxicity. The aqueous solubility of DG was determined to be 0.7 ng/ml (1.69 nm).[9] It was also revealed that the low solubility of DG led to poor bioavailability and gastrointestinal mucosal toxicity. [10] As poor solubility has been recognized as a frequently encountered challenge in the field of pharmaceutics, different approaches have been employed to improve the solubility and bioavailability of poorly watersoluble compounds including DG. [11] For instance, an inclusion of complexation of DG and β-cyclodextrin was formed. [12] Iron oxide nanoparticles loaded with DG were prepared. [13] Improving the solubility of DG and decreasing its intrinsic cytotoxicity or at least avoiding any additional toxicity against normal cells are the major challenges to its biomedical application. Numerous efforts have been made to chemically modify this compound to improve its applicable biological activities. Diosgenyl saponin, dioscin analogues were designed to improve its anticancer a...

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Effect of β-Cyclodextrin Derivatives on the Diosgenin Absorption in Caco-2 Cell Monolayer and Rats

Cited by 24 publications

References 19 publications

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

Diosgenin: Recent Highlights on Pharmacology and Analytical Methodology

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

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