Li S et al. (2016), Absorption and Transport of Sea Cucumber Saponi...

ECB-ART-44765

Mar Drugs 2016 Jun 17;146:. doi: 10.3390/md14060114.

Show Gene links Show Anatomy links

Absorption and Transport of Sea Cucumber Saponins from Apostichopus japonicus.

Li S , Wang Y , Jiang T , Wang H , Yang S , Lv Z .

???displayArticle.abstract???
The present study is focused on the intestinal absorption of sea cucumber saponins. We determined the pharmacokinetic characteristics and bioavailability of Echinoside A and Holotoxin A₁; the findings indicated that the bioavailability of Holotoxin A₁ was lower than Echinoside A. We inferred that the differences in chemical structure between compounds was a factor that explained their different characteristics of transport across the intestine. In order to confirm the absorption characteristics of Echinoside A and Holotoxin A₁, we examined their transport across Caco-2 cell monolayer and effective permeability by single-pass intestinal perfusion. The results of Caco-2 cell model indicate that Echinoside A is transported by passive diffusion, and not influenced by the exocytosis of P-glycoprotein (P-gp, expressed in the apical side of Caco-2 monolayers as the classic inhibitor). The intestinal perfusion also demonstrated well the absorption of Echinoside A and poor absorption of Holotoxin A₁, which matched up with the result of the Caco-2 cell model. The results demonstrated our conjecture and provides fundamental information on the relationship between the chemical structure of these sea cucumber saponins and their absorption characteristics, and we believe that our findings build a foundation for the further metabolism study of sea cucumber saponins and contribute to the further clinical research of saponins.

???displayArticle.pubmedLink??? 27322290
???displayArticle.pmcLink??? PMC4926073
???displayArticle.link??? Mar Drugs

Genes referenced: LOC100887844 LOC115919910 LOC582726

???attribute.lit??? ???displayArticles.show???

References [+] :

Aminin, Immunomodulatory Properties of Cucumariosides from the Edible Far-Eastern Holothurian Cucumaria japonica. 2001, Pubmed, Echinobase

Aminin, Immunomodulatory Properties of Cucumariosides from the Edible Far-Eastern Holothurian Cucumaria japonica. 2001, Pubmed , Echinobase
Artursson, Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. 1991, Pubmed
Artursson, Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. 1990, Pubmed
Bordbar, High-value components and bioactives from sea cucumbers for functional foods--a review. 2011, Pubmed , Echinobase
Borlak, Expression of drug-metabolizing enzymes, nuclear transcription factors and ABC transporters in Caco-2 cells. 2003, Pubmed
Cattoor, Transport of hop bitter acids across intestinal Caco-2 cell monolayers. 2010, Pubmed
Cook, Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat. 2003, Pubmed
Fossati, Use of simulated intestinal fluid for Caco-2 permeability assay of lipophilic drugs. 2008, Pubmed
Han, [Mechanism of oral absorption of panaxnotoginseng saponins]. 2006, Pubmed
Han, Antifungal active triterpene glycosides from sea cucumber Holothuria scabra. 2009, Pubmed , Echinobase
Hill, Triterpenoids. 2012, Pubmed
Hillgren, In vitro systems for studying intestinal drug absorption. 1995, Pubmed
Hu, Soyasaponin I and sapongenol B have limited absorption by Caco-2 intestinal cells and limited bioavailability in women. 2004, Pubmed
Kalinin, Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: some trends in the evolution of this group of toxins. 1996, Pubmed , Echinobase
Kerr, In vivo and in vitro biosynthesis of saponins in sea cucumbers. 1995, Pubmed , Echinobase
Kitagawa, Saponin and sapogenol. XV. Antifungal glycosides from the sea cucumber Stichopus japonicus selenka. (2). Structures of holotoxin A and holotoxin B. 1976, Pubmed , Echinobase
Lau, Evaluation of a novel in vitro Caco-2 hepatocyte hybrid system for predicting in vivo oral bioavailability. 2004, Pubmed
Levitt, Use of laminar flow and unstirred layer models to predict intestinal absorption in the rat. 1988, Pubmed
Lu, Transport properties are not altered across Caco-2 cells with heightened TEER despite underlying physiological and ultrastructural changes. 1996, Pubmed
Maubon, Analysis of drug transporter expression in human intestinal Caco-2 cells by real-time PCR. 2007, Pubmed
Murota, Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids. 2002, Pubmed
Odani, Studies on the absorption, distribution, excretion and metabolism of ginseng saponins. II. The absorption, distribution and excretion of ginsenoside Rg1 in the rat. 1983, Pubmed
Palmgrén, Characterization of Caco-2 cell monolayer drug transport properties by cassette dosing using UV/fluorescence HPLC. 2004, Pubmed
Park, Relationships between chemical structures and functions of triterpene glycosides isolated from sea cucumbers. 2014, Pubmed , Echinobase
Prokof'eva, Biological activities of steroid glycosides from starfish. 2003, Pubmed , Echinobase
Salphati, Evaluation of a single-pass intestinal-perfusion method in rat for the prediction of absorption in man. 2001, Pubmed
Song, Intestinal permeability of metformin using single-pass intestinal perfusion in rats. 2006, Pubmed
Sparg, Biological activities and distribution of plant saponins. 2004, Pubmed
Sutton, Comparison of the gravimetric, phenol red, and 14C-PEG-3350 methods to determine water absorption in the rat single-pass intestinal perfusion model. 2001, Pubmed
Walgren, Transport of quercetin and its glucosides across human intestinal epithelial Caco-2 cells. 1998, Pubmed
Walter, Transport of peptidomimetic renin inhibitors across monolayers of a human intestinal cell line (Caco-2): evidence for self-enhancement of paracellular transport route. 1995, Pubmed
Zakeri-Milani, Predicting human intestinal permeability using single-pass intestinal perfusion in rat. 2007, Pubmed
Zou, Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert. 2003, Pubmed , Echinobase

	Figure 1. ESI-MS spectra of Echinoside A in negative mode.
	Figure 2. Chemical structure of Holotoxin A1.
	Figure 3. Chemical structure of Echinoside A.
	Figure 4. HPLC-chromatogram of Echinoside A and Holotoxin A1.
	Figure 5. (a) Plasma concentrations-time curves of Echinoside A after oral administration; (b) plasma concentrations-time curves of Echinoside A after intravenous administration; and (c) plasma concentrations-time curves of Holotoxin A1 after intravenous administration. (means ± SD, n = 5).
	Figure 6. (a) AP-to-BL transport of different concentration of Echinoside A across Caco-2 monolayers; and (b) BL-to-AP transport of different concentration of Echinoside A across Caco-2 monolayers, (means ± SD, n = 3).

	Figure 8. Peff values of Echinoside A and Holotoxin A1 at 1, 5, 25 μg/mL, as well as 50 μg/mL with the addition of verapamil using single-pass intestinal perfusion (means ± SD, n = 5).