Abstract 501: Poly Herbal Formulation Prevents Foam Cell Formation Possibly Through Attenuation of CD36 Scavenger Receptor Signalling Cascade

Abstract

Objective CD36 signalling cascade promotes migration, spreading and entrapment of lipid laden foam cells within intimal lesions by oxidative stress, inflammation and oxidized LDL (oxLDL) by activation of actin polymerization, Focal Adhesion Kinase (FAK) and cement adhesion which also are indirectly activated by Reactive Oxygen Species (ROS). There is dearth of information about an antagonistic therapy for this CD36 cascading pathway to prevent atherosclerosis. Therefore, we hypothesized that, an antioxidant, antiinflammatory and antihyperlipidemic Poly Herbal Formulation (PHF) consisting of Allium sativum, Zingiber officinale, Curcuma longa, Terminalia arjuna and Cyprus rotundus prevents atherosclerosis. Methods Standardized (WHO and IP monographs) hydro-alcoholic extracts of the above said test materials were mixed in equal amounts to prepare PHF. After conforming the antioxidant, antiinflammatory and antihyperlipidemic activities, PHF was evaluated for foam cell formation and the protein expression of CD36, PPAR-γ and FAK in oxLDL treated mouse macrophage J774A.1 cells. Its inhibitory activity for ROS generation was evaluated. Antiatherosclerotic activity was studied in high cholesterol fed rabbit model. Results Significant accrual of lipid in oxLDL treated cells conform the foam cell formation where CD36, PPAR-γ and FAK protein levels had increased. PHF (20 to 80 μg/mL) prevented lipid accumulation in oxLDL treated cells from ~29% to ~38% where CD36, PPAR-γ and FAK protein levels were significantly decreased in concentration dependent manner up to 3, 2 and 2 folds, respectively. ROS generation was inhibited by PHF in concentration dependent manner. PHF dose of 100 and 200mg/Kg, significantly reduced plasma cholesterol, ~23% and ~40% and plasma triglycerides ~87% and ~91%, respectively. Plasma TBARS were significantly reduced by PHF 100 and 200mg/Kg, 50% and ~66%, respectively. Aortic atheroma formation was significantly barred by PHF as observed in histopathological studies. Conclusion PHF prevents atherosclerosis by preventing foam cell formation possibly by reducing CD36, PPAR-γ and FAK proteins and ROS generation. However, detailed pharmacodynamic studies are needed to correlate these findings in a clinical set up.