Opuntiol and opuntioside-I an anti-atherogenic agent interfering with chemotaxis via IPLA₂B-dependent F-actin polymerization in human monocyte

Opuntia dilleni (KER-GAW) HAW belongs to the genus Opuntia (Fam. Cactaceae) and has shown remarkable effects as an anti-inflammatory agent. In this study we evaluate the effect of opuntiol and opuntioside-I against MCP-1 dependent chemotaxis. Monocytes Chemoattractant Protein-1 (MCP-1) being a β-chemokine exhibits chemotactic activity via activating signal transducing phospholipases (PLA₂) calcium independent iPLA₂β and calcium dependent cPLA₂α. We discovered earlier that MCP-1 induces association of iPLA₂β with F-actin and actin polymerization is significantly reduced due to inhibition of iPLA₂β or its reduced expression. In the present investigation we identified opuntiol and opuntioside-I reduced human monocyte migration (50–90%) dose dependently (2.5–10mM) against MCP-1 in microchamber chemotaxis assay. Laser scanning confocal microscopy demonstrated opuntiol and opuntioside-I interfered with iPLA₂β translocation to cell membrane in MCP-1 stimulated migrating cells and suppressed migration under agarose assay. Furthermore, MCP-1 induced- and iPLA₂β dependent-actin polymerization was also inhibited in cells treated with 10 μM of opuntioside-I. F-actin polymerization was studied using phalloidin staining of filaments. In adoptive transfer mouse model, opuntiol and opuntioside-I (10 μg/mL) inhibited cell migration by 80% during thioglycolate induced peritonitis. These compounds (20 mg/kg) were also found to be effective upon oral treatment in mouse peritonitis model. Our results suggest that opuntiol and opuntioside-I interfere with phospholipase A2 signaling in MCP-1 stimulated monocyte via inhibiting iPLA₂β activity. We can conclude that these compounds are potential therapeutic agents to reduce MCP-1 dependent monocyte migration and its related immune and inflammatory diseases, e.g., atherosclerosis.