Immunomodulatory Properties of Cucumariosides from the Edible Far-Eastern Holothurian Cucumaria japonica

Abstract

Holothurian triterpene glycosides (cucumariosides) are known to possess multiple biological activities. Here we show that cucumariosides from the Far Eastern edible holothurian (sea cucumber), Cucumaria japonica, and their semisynthetic derivatives possess potent immunomodulatory properties. Intraperitoneal injection of cucumariosides (0.2-20 ng per mouse) induced macrophage lysosomal activity in a dose-dependent manner (up to 250% of control). The stimulatory effect was related to the chemical structure of cucumariosides and was especially influenced by the number and position of sulfate groups in the carbohydrate moiety of the molecules. In vitro, an inhibitory rather than a stimulatory effect of cucumariosides on phagocytosis and release of tumor necrosis factor-alpha (TNF-alpha) was found. Virtually all cucumariosides inhibited latex bead phagocytosis by human peripheral blood granulocytes in a dose-dependent manner. Also, the lipopolysaccharide-induced TNF-alpha production by immune cells in human blood diluted with RPMI-1640 was decreased, without a clear relation to the structure and dose of the compounds. The data are discussed in terms of possible mechanisms underlying immunomodulatory properties of triterpene glycosides from C. japonica.

Anti-cancer Effects of Triterpene Glycosides, Frondoside A and Cucumarioside A2-2 Isolated from Sea Cucumbers

“…Similar results were reported by Miamoto et al They demonstrated that the desulfated derivatives inhibit more significantly tumor cell growth than glycosides with C-6 sulfates in monosaccharide units [26]. In comparison to anti-cancer activity, the macrophage lysosomal activity and increase of intracellular Ca ++ concentrations were also demonstrated to be related to chemical structures of Cucumariosides and be influenced by the number and positions of sulfate groups in the carbohydrate moiety of the molecules [27,28]. On the other hands, Cucumarioside A 2 -2 was the most active in inducing a rapid increase in cytosolic Ca ++ content, when compared to the polysulfated derivative of A 2 -2 [28].…”

“…Our study also indicated that the acetyl group at C-16 of the aglycone in Frondoside A may play a significant role in Frondoside A cytotoxicity since Frondoside A has more potent effects than Cucumarioside A 2 -2 on cytotoxicity, cell cycle changes and apoptosis [13]. Similarly, monosulfated Cucumariosides A 2 -2 and A 4 -2 were among the most active compounds for stimulating peritoneal macrophage lysosomal activity, while desulfation of their carbohydrate moiety completely abolished this activity [27]. However, they demonstrated that lysosomal activity and cytoxicity of cucumariosides depends on structures of both aglycone and carbohydrate chain but there is no direct correlation between two activities of the glycosides [34].…”

“…The LD 50 of Frondoside A and Cucumarioside A 2 -2 for mice was 9.9 mg/kg and 10 mg/kg, respectively after intraperitoneal injection [27,29]. This suggests that acute toxicity for these two compounds is similar and generally low.…”

Nutritional Composition of Selected Species of Sea cucumbers from Waters around Jaffna Peninsula, Sri Lanka

“…*Correspondence: ketharani@gmail.com modulatory activities due to the presence of compounds such as sulponamides and diketones (Aminin et al, 2001). Many Asians believe sea cucumbers should be eaten to treat ailments such as cancer and arthritis, as well as intestinal and urinary dysfunctions (Purcell, 2010).…”

Immunomodulatory Properties of Sea Cucumber Triterpene Glycosides

“…The effect was seen at picogram doses of cucumariosides with a maximum stimulation around 20 ng/mouse (Aminin et al 2001).…”