title: Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in apolipoprotein-E knockout mice fed a high cholesterol diet.
abstract: Tanshinone II-A (Tan), a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen), possesses anti-oxidant and anti-inflammatory activities. The present study investigated whether Tan can decrease and stabilize atherosclerotic plaques in Apolipoprotein-E knockout (ApoE(-/-)) mice maintained on a high cholesterol diet (HCD). Six week-old mice challenged with a HCD were randomly assigned to 4 groups: (a) C57BL/6J; (b) ApoE(-/-); (c) ApoE(-/-)+Tan-30 (30 mg/kg/d); (d) ApoE(-/-)+Tan-10 (10mg/kg/d). After 16 weeks of intervention, Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and en face aorta. Furthermore, immunohistochemical analysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by reduced necrotic cores, decreased macrophage infiltration, and increased smooth muscle cell and collagen contents. Tan also significantly reduced in situ superoxide anion production, aortic expression of NF-κB and matrix metalloproteinase-9 (MMP-9). In vitro treatment of RAW264.7 macrophages with Tan significantly suppressed oxidized LDL-induced reactive oxygen species production, pro-inflammatory cytokine (IL-6, TNF-α, MCP-1) expression, and MMP-9 activity. Tan attenuates the development of atherosclerotic lesions and promotes plaque stability in ApoE(-/-) mice by reducing vascular oxidative stress and inflammatory response. Our findings highlight Tan as a potential therapeutic agent to prevent atherosclerotic cardiovascular diseases.
authors: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University (HEMC), 132 East Wai-huan Road, Guangzhou, Guangdong, China.
authors: Suowen
authors: S
authors: Xu
authors: Peter J
authors: PJ
authors: Little
authors: Tian
authors: T
authors: Lan
authors: Yan
authors: Y
authors: Huang
authors: Kang
authors: K
authors: Le
authors: Xiaoqian
authors: X
authors: Wu
authors: Xiaoyan
authors: X
authors: Shen
authors: Heqing
authors: H
authors: Huang
authors: Yi
authors: Y
authors: Cai
authors: Futian
authors: F
authors: Tang
authors: Hua
authors: H
authors: Wang
authors: Peiqing
authors: P
authors: Liu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D045784:Abietanes; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; C021751:tanshinone