Owais Mohammad Bhat1, P Uday Kumar2, K Rajender Rao3, Ashfaq Ahmad1, Veena Dhawan4. 1. Department of Pharmcology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA. 2. Department of Histopathology, National Institute of Nutrition (NIN), Hyderabad, India. 3. National Centre for Laboratory Animal Sciences (NCLAS), National Institute of Nutrition (NIN), Hyderabad, India. 4. Department of Experimental Medicine and Biotechnology, Research Block-B, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India. veenad2001@yahoo.com.
Abstract
AIM OF THE STUDY: 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-κB/PPAR-γ-mediated pathway in Apo E-/- mice. MATERIALS AND METHODS: 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). RESULTS: 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-γ) 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. CONCLUSION: Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway.
AIM OF THE STUDY: 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-κB/PPAR-γ-mediated pathway in Apo E-/- mice. MATERIALS AND METHODS: 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). RESULTS: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-γ) 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. CONCLUSION: Our data demonstrate that TAE protects against IL-18-induced atherosclerosis via NF-κB/PPAR-γ-mediated pathway.
Authors: Y Gu; K Kuida; H Tsutsui; G Ku; K Hsiao; M A Fleming; N Hayashi; K Higashino; H Okamura; K Nakanishi; M Kurimoto; T Tanimoto; R A Flavell; V Sato; M W Harding; D J Livingston; M S Su Journal: Science Date: 1997-01-10 Impact factor: 47.728