Opuntiol and Opuntioside-I an anti-atherogenic agent interfering with Chemotaxis via iPLA2β-dependent F-actin polymerization in human monocyte

Session: 
Poster Session
Author(s): 
ROOME, Talat - Molecular Pathology, Department of Pathology, Dow diagnostic Reference and Research Laboratory, Dow International Medical College, Dow University of Health Sciences Karachi, Pakistan.
Saeed KHAN - Molecular Pathology, Department of Pathology, Dow diagnostic Reference and Research Laboratory, Dow International Medical College, Dow University of Health Sciences Karachi, Pakistan
Anam RAZZAK - Molecular Pathology, Department of Pathology, Dow diagnostic Reference and Research Laboratory, Dow International Medical College, Dow University of Health Sciences Karachi, Pakistan
Ayaz NOORANI - Molecular Pathology, Department of Pathology, Dow diagnostic Reference and Research Laboratory, Dow International Medical College, Dow University of Health Sciences Karachi, Pakistan
Rafiq KHANANI - Molecular Pathology, Department of Pathology, Dow diagnostic Reference and Research Laboratory, Dow International Medical College, Dow University of Health Sciences Karachi, Pakistan
Ahsana DAR - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan
Shaheen FAIZI - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan
Lubna ABIDI - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan
Lubna - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan
Martha CATHCART - Department of Cell Biology, Cleveland Clinic Lerner Research Institute, Cleveland Clinic Foundation, OH, USA.

Opuntia dilleni have shown remarkable effects as anti-diabetic, anti-oxidant, anti-hypotensive, anti-inflammatory and anti-viral agent. We identified opuntiol and opuntioside-I reduced human monocyte migration (50-90%) dose dependently (2.5-10 µM) against MCP-1. Laser Scanning Confocal Microscopy demonstrated Opuntiol and Opuntioside-I interfered with iPLA2β translocation to cell membrane in MCP-1 stimulated migrating cells using specific antibodies with fluorescent dye and its gradient dependent migration under-agarose assay was also suppressed. 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 fillaments. In adoptive transfer mouse model, Opuntiol and Opuntioside-I at 10 µg/ml inhibited cell migration by 80%. These compounds (20mg/kg) were also found to be effective upon oral treatment in mouse peritonitis model. These results suggest that Opuntiol and Opuntioside-I interfere with phospholipase A2 signaling in MCP-1 stimulated monocyte via inhibiting iPLA2β activity.