Terminalia arjuna prevents Interleukin-18-induced atherosclerosis via modulation of NF-κB/PPAR-γ-mediated pathway in Apo E-/- mice

Terminalia arjuna is a medicinal plant well known as a cardiotonic in Ayurvedic system of medicine. We hypothesized that aqueous stem bark extract of T. arjuna (TAE) may inhibit IL-18-induced atherosclerosis via NF-kappa B/PPAR-gamma-mediated pathway in Apo E-/- mice. 12-week-old, male Apo E-/- mice divided into four groups (n = 6/group) fed with normal chow-diet were employed: GP I: phosphate buffer saline (PBS) (2 month); GP II: rIL-18 (1 month) followed by PBS (1 month); GP III: rIL-18 (1 month) followed by TAE (1 month); GP IV: rIL-18 (1 month) followed by atorvastatin (1 month). IL-18 treatment induced a significant increase (p < 0.001) in pro-inflammatory marker (IL-18) (170 +/- 9.16 vs. 1178.66 +/- 8.08, pg/ml), and downregulated cholesterol efflux gene (PPAR-gamma) by 0.6-fold vs. 1.00 in IL-18-treated mice as compared to the control animals, respectively. TAE treatment to both groups caused a significant reduction in IL-18 to 281.66 +/- 9.60 vs. 1178.66 +/- 8.08 (pg/ml), upregulated cholesterol efflux gene by 1.5- vs. 0.6-fold in TAE-treated group, decreased atherogenic lipids, and percentage atherosclerotic lesion area, demonstrating comparable effects with atorvastatin. Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-kappa B/PPAR-gamma-mediated pathway. [GRAPHICS] .