Immunomodulatory Properties of Frondoside A, a Major Triterpene Glycoside from the North Atlantic Commercially Harvested Sea Cucumber Cucumaria frondosa

Abstract

Frondoside A, a major triterpene glycoside from North Atlantic commercially harvested sea cucumber Cucumaria frondosa, possesses strong immunomodulatory properties in subtoxic doses. Frondoside A stimulates lysosomal activity of mouse macrophages in vivo at a maximal effective stimulatory dose of 0.2 microg per mouse and is maintained over 10 days. This glycoside also shows a 30% stimulation of lysosomal activity in mouse macrophages in vitro at concentrations of 0.1-0.38 microg/mL. Frondoside A enhances macrophage phagocytosis of the bacterium Staphylococcus aureus in vitro at a maximal effective concentration of 0.001 microg/mL. Frondoside A stimulates reactive oxygen species formation in macrophages in vitro at a maximal effective concentration of 0.001 microg/mL. Frondoside A stimulates an increase in the number of antibody plaque-forming cells (normally B-cells in spleen) in vivo with a maximal stimulatory effect at a concentration of 0.2 microg per mouse (stimulatory index, 1.86). Frondoside A has a weak effect upon immunoglobulin (Ig) M production after immunization with sheep erythrocytes in mice. Frondoside A does not stimulate Ig production in mice and does not significantly enhance the ovalbumin-stimulated IgM and IgG antibody levels in ovalbumin-immunized mice. Hence frondoside A is an immunostimulant of cell-based immunity including phagocytosis without a significant effect on amplification of humoral immune activity or adjuvant properties. Therefore, frondoside A may provide curative and/or preventive treatment options against diseases wherein a depleted immune status contributes to the pathological processes.

Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades

“…For instance, Frondoside A 43 , reported as the major triterpene glycoside from sea cucumber Cucumaria frondosa, possesses immunomodulatory properties [124]. This group suggested that Frondoside A 43 induced prolonged lysosomal activity of mouse macrophages in vivo and in vitro with different concentrations, and stimulated the phagocytosis process of macrophages.…”

Improved Innate Immune Responses by Frondanol A5, a Sea Cucumber Extract, Prevent Intestinal Tumorigenesis

“…The reduction primarily occurs through growth inhibition and induction of apoptosis (12). Further, Collin et al demonstrated that Frondoside A, a component of Frondanol ® A5, inhibited microtubule formation in an angiogenesis assay, and also stimulated innate immunity in vivo (33-34). Dietary supplementation of Frondanol ® A5 in combination with other natural agents enhanced its anti-inflammatory properties (35).…”

Characterization and comparison of proteomes of albino sea cucumber Apostichopus japonicus (Selenka) by iTRAQ analysis

“…In a typical procedure, frozen mixed intestines and frozen mixed body walls from treatment and control groups were ground well to powder with a cold mortar and pestle, and kept in a liquid nitrogen bath in a styrofoam box during the entire procedure [13]. Protein concentration was determined by the Bradford colorimetric method (Bio-Rad) following standard protocol.…”

“…A total of six samples were obtained for each group in the end. The M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 7 samples were homogenized with a cold mortar and pestle in a liquid nitrogen bath [13]. And total RNA was extracted using RNAiso Plus (TaKaRa Bio Group, DaLian).…”