title: Lactones from Ligusticum chuanxiong Hort. reduces atherosclerotic lesions in apoE-deficient mice via inhibiting over expression of NF-kB-dependent adhesion molecules.
abstract: 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-κB 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 α (TNF-α) was measured by ELISA. And the activation of NF-κB 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-κB) in the atherosclerotic plaque. Moreover, LLC at 3.125-25 μg/mL can dose-dependently attenuate the expression of ICAM-1 and VCAM-1 in TNF-α stimulated HUVECs. Western blot result indicated LLC inhibited activation of NF-κB. 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-κB-dependent adhesion molecules.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Lai-Lai
authors.initials: LL
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ye-Cheng
authors.initials: YC
authors.lastname: Jin
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
authors.affiliation: Department of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: vip_wangyi@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D030004:Ligusticum / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010946:Plants, Medicinal; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D007783:Lactones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: Adhesion molecule; ApoE(−/−); HUVEC; Lactones; NF-κB; TNF-α