holothurin and stichoposide

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.

Topics: Animals; Biological Availability; Biological Transport; Caco-2 Cells; Cell Line, Tumor; Glycosides; Holothurin; Humans; Intestinal Absorption; Intestinal Mucosa; Male; Rats; Rats, Wistar; Saponins; Sea Cucumbers; Stichopus; Triterpenes

Escherichia coli heat-labile enterotoxin B subunit (LTB) (2 micrograms), supplemented with a trace amount of the holotoxin (LT) (0.02-20 ng), was examined for the adjuvant effect on antibody (Ab) responses against influenza inactivated haemagglutinin (HA) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5 micrograms), prepared from PR8 (H1N1) virus, together with LT-containing LTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The inoculation of the vaccine with the LT-containing LTB induced significantly high primary and secondary anti-HA IgA and IgG Ab responses in the nasal wash and the serum, while the vaccine with LTB or less than 2 ng of LT induced little response. The synergistic adjuvant effect was maximal in the concentration of LTB supplemented with 0.2-2 ng of LT. Under these conditions, the augmented IgA and IgG Ab responses, which are cross-protective to PR8 HA molecules, provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccine within the same subtype. These results suggest that LTB containing a trace amount of LT can be used as a potent adjuvant for nasal vaccination of humans against influenza.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Viral; Bacterial Toxins; Dose-Response Relationship, Immunologic; Drug Synergism; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Escherichia coli Proteins; Female; Glycosides; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Holothurin; Humans; Immunoglobulin A; Immunoglobulin G; Influenza Vaccines; Influenza, Human; Mice; Mice, Inbred BALB C; Orthomyxoviridae; Recombinant Proteins; Sea Cucumbers; Triterpenes

The membrane activity of 6 triterpenic glycosides was studied with respect to ionic permeability of the liposomes and flat bilayer lipid membranes. It was shown that the rate of the glycoside effect depended on both the sterol level in the membrane and the sterol type (cholesterol, ergosterol). The activity of cauloside C, a plant glycoside markedly depended on pH of the medium. The carbohydrate chain played an important role in the membrane activity of the glycosides. Correlation in the effect of triterpenic glycosides on the model lipid and cell membranes was noted.

Topics: Cell Membrane; Glycosides; Holothurin; Lipid Bilayers; Liposomes; Marine Toxins; Oleanolic Acid; Saponins; Structure-Activity Relationship; Triterpenes