Recent Advances in Researches on Physiologically Active Substances in Holothurians

In this report, we reviewed recent literature on physiologically active substances from sea cucumbers (SCs) andtheir activities together with results obtained from our study. Preventive properties against lipid metabolism were reported inrats using a whole SC preparation with no particular constituent specified. Administration of the preparation lowered serumand hepatic cholesterol levels and improved the HDL/LDL ratio. These functions may be attributed to the stimulatory effectof the extract on the secretion of cholesterol in feces. Novel fucosylated chondroitin sulfates (FCSs) from Ludwigothureagrisea significantly induced fibroblast growth factor 2-dependent angiogenesis in human umbilical vein endothelial cells (HU-VECs). The proangiogenetic activity seemed attributable to the action of the sulfated fucose branches on the polysaccharide.SCs contain mycosporine-like amino acids (MAAs) that are capable of absorbing UV. A biogenetic precursor of MAAs wasfirst reported in SCs. The anti-proliferative effects of a branched chain fatty acid from a sea cucumber on prostate cancercells was reported with the activity of 5-lipoxygenase. Glycosphingolipid constituents in SCs have been systematically ana-lyzed over the past ten years. The results showed that the gangliosides in several SCs differed from those of mammals in thata sialic acid of SC gangliosides directly binded to glucose of cerebroside. Neuritogenic activity of the glycosphingolipids wasdemonstrated in vitro experiments and may lead to the development of therapeutic products for neurological disorders. Ourstudy also showed that sphingoid bases, the hydrolyzed products of glycosphingolipids from SCs, induced significant apoptosisin several tumor cell lines.

Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria.In this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in periodontitis.Minimal inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against P.gingivalis,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely important.Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane.This information,coupled with the association of treatment lipids with P.gingivalis lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial activity.Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P.gingivalis stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and virulence.Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.