PMID- 24594239 OWN - NLM STAT- MEDLINE DCOM- 20150107 LR - 20140507 IS - 1873-6971 (Electronic) IS - 0367-326X (Linking) VI - 95 DP - 2014 Jun TI - Lactones from Ligusticum chuanxiong Hort. reduces atherosclerotic lesions in apoE-deficient mice via inhibiting over expression of NF-kB-dependent adhesion molecules. PG - 240-6 LID - S0367-326X(14)00057-4 [pii] LID - 10.1016/j.fitote.2014.02.012 [doi] AB - The present study aims to investigate the anti-atherosclerotic effects of lactones extracted from Ligusticum chuanxiong Hort (LLC) in apoE-deficient mice (ApoE(-/-) mice) and proclaim its underlying mechanisms. Expression of endothelial adhesion molecules and NF-kappaB around the atherosclerotic lesions was detected by immunohistochemistry (IHC). To further validate the mechanism, effect of LLC on the secretion of ICAM-1 and VCAM-1 of human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor alpha (TNF-alpha) was measured by ELISA. And the activation of NF-kappaB was detected by western blot. Mice treated with LLC showed significant reduction in lesion sizes of thoracic segments of the aorta (p<0.01). Meanwhile, LLC treatments lead to decreases of serum TG, TC and LDL-C contents, respectively. LLC also decreased the expression of CD31, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappa B (NF-kappaB) in the atherosclerotic plaque. Moreover, LLC at 3.125-25 mug/mL can dose-dependently attenuate the expression of ICAM-1 and VCAM-1 in TNF-alpha stimulated HUVECs. Western blot result indicated LLC inhibited activation of NF-kappaB. These results suggested that LLC could ameliorate atherosclerosis in ApoE(-/-) mice. The mechanism of action of LLC on anti-atherosclerotic effect may be attributed to the suppression of the production of NF-kappaB-dependent adhesion molecules. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Xiao, Yang AU - Xiao Y AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. FAU - Wang, Ying-Chao AU - Wang YC AD - Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Li, Lai-Lai AU - Li LL AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. FAU - Jin, Ye-Cheng AU - Jin YC AD - Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Sironi, Luigi AU - Sironi L AD - Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy. FAU - Wang, Yi AU - Wang Y AD - Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Wang, Yi AU - Wang Y AD - Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: vip_wangyi@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140302 PL - Netherlands TA - Fitoterapia JT - Fitoterapia JID - 16930290R RN - 0 (Apolipoproteins E) RN - 0 (Cell Adhesion Molecules) RN - 0 (Lactones) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM EIN - Fitoterapia. 2014 Jul;96:159 MH - Animals MH - Aorta/pathology MH - Apolipoproteins E/genetics MH - Atherosclerosis/*drug therapy MH - Cell Adhesion Molecules/*metabolism MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Disease Models, Animal MH - Down-Regulation/drug effects MH - Gene Expression Regulation/*drug effects MH - Human Umbilical Vein Endothelial Cells/drug effects/metabolism MH - Humans MH - Lactones/chemistry/isolation & purification/*therapeutic use MH - Ligusticum/*chemistry MH - Mice MH - Mice, Knockout MH - NF-kappa B/*drug effects/metabolism MH - Plants, Medicinal MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Adhesion molecule OT - ApoE(-/-) OT - HUVEC OT - Lactones OT - NF-kappaB OT - TNF-alpha EDAT- 2014/03/07 06:00 MHDA- 2015/01/08 06:00 CRDT- 2014/03/06 06:00 PHST- 2013/12/23 00:00 [received] PHST- 2014/02/20 00:00 [revised] PHST- 2014/02/22 00:00 [accepted] PHST- 2014/03/06 06:00 [entrez] PHST- 2014/03/07 06:00 [pubmed] PHST- 2015/01/08 06:00 [medline] AID - S0367-326X(14)00057-4 [pii] AID - 10.1016/j.fitote.2014.02.012 [doi] PST - ppublish SO - Fitoterapia. 2014 Jun;95:240-6. doi: 10.1016/j.fitote.2014.02.012. Epub 2014 Mar 2.