Glycosides from edible sea cucumbers stimulate macrophages via purinergic receptors

Abstract

Since ancient times, edible sea cucumbers have been considered a jewel of the seabed and used in Asian folk medicine for stimulation of resistance against different diseases. However, the power of this sea food has not been established on a molecular level. A particular group of triterpene glycosides was found to be characteristic metabolites of the animals, responsible for this biological action. Using one of them, cucumarioside A2-2 (CA2-2) from the edible Cucumaria japonica species as an example as well as inhibitory analysis, patch-clamp on single macrophages, small interfering RNA technique, immunoblotting, SPR analysis, computer modeling and other methods, we demonstrate low doses of CA2-2 specifically to interact with P2X receptors (predominantly P2X4) on membranes of mature macrophages, enhancing the reversible ATP-dependent Ca2+ intake and recovering Ca2+ transport at inactivation of these receptors. As result, interaction of glycosides of this type with P2X receptors leads to activation of cellular immunity.

Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity

“…Compounds with immunomodulatory activities have been isolated from edible sea cucumber species such as Cucumaria japonica, C. frondosa and Stichopus japonicus (Aminin et al, 2016; Aminin et al, 2008; Aminin et al, 2006; Song, Y. et al, 2013). Among these anti-infective molecules, polysaccharides are the most studied group (Kale et al, 2013; Song, Y. et al, 2013; Wang et al, 2017).…”

“…In addition, some triterpene glycosides, which are prominent secondary metabolites in sea cucumbers, also possessed immune-boosting effects (Bahrami and Franco, 2016). Two examples, cucumariosides and frondoside, were also reported to promote cellular immunity through stimulation of phagocystosis and lysosomal activities (Aminin et al, 2016; Aminin et al, 2001; Aminin et al, 2008). In our case, the main constituents detected in the bioactive H. atra fraction are aspidospermatidine and inosine.…”

“…Among the many medicinal properties linked with sea cucumbers, sea cucumbers are also traditionally consumed for its immune boosting properties (Chen, 2004). In tandem, metabolites with in vitro or in vivo immunomodulatory activities have been isolated from several sea cucumber species (Aminin et al, 2016; Aminin et al, 2008; Aminin et al, 2006; Song, Y. et al, 2013). Therefore, sea cucumber is an opportune organism for discovery of novel and potent anti-infective entities.…”

Toxic Properties of Holothurian’s Triterpene Glycosides

“…Это приводит к усилению адгезии клеток и их пролиферации, формированию в них активных форм кислорода, увеличению лизосомальной активности, фагоцитоза и синтеза некоторых цитокинов. В конечном итоге происходит активирование всего клеточного звена иммунитета [67]. В то же время обнаружено, что иммуномодулирующая активность тритерпеновых зависит от их химической структуры и наличия в них сульфатных групп.…”

Sulfated Glycosides from the Sea Cucumbers Block Ca2+ Flow in Murine Neuroblastoma Cells

“…The membrane targets of glycoside action are the purinergic receptors of the P2X family (P2X1 and P2X4 types) that provide Ca 2+ conductivity in the macrophage membranes. The immunomodulatory effect of cucumarioside A 2 -2 is observed due to its action as an allosteric modulator of purinergic receptors, binding to them and enhancing the response of cells to ATP [4][5][6][7][8][9].…”